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Physio Block 3 Endo
Endocrinology for the UT Southwestern spring 2010 Physiology Course
| Question | Answer |
|---|---|
| Hypothalamus Development | diencephalon, forms floor & part of latter wall of 3d ventricle |
| Pituitary Gland Development | Epithelial cells from posterior pharynx -> Rathke's Pouch (adenohypophysis = anterior pit. 80%), interfaces w/infundibulum (neurohypophysis = posterior pit. 20%). |
| HPT axes (Hypothalamus-Pituitary-Target Organ) exceptions | Exceptions = Parathyroid Gland, Adrenal Medulla & Zona Glomerulosa, Placenta, Pancreas. |
| Which hormones are made in the PVN? | THRH, CRH, Somatostatin (inhibitory for GH) |
| Which hormones are made in the ARC? | GnRH & LH, GHRH, DA (inhibitory for PRL) |
| What characterizes the portal Veins of the Infundibulum? | Low pressure, form sinusoids in ant. pit. |
| Which hormones are made of 2 peptide chains? | TSH, LH, FSH, Human Chorionic Gonadotropin, Activins, Inhibins |
| HPT axis | (DA/Somatostatin/CORT inhibit; cold stimulates) TRH release (not pulsatile)-> Gs R (15% of ant. pit.)-> TSH -> T3/T4 & PRL. Feedback Inhibition @ hypothalamus & pit. half-life = days, single measure sufficient. |
| HPA Axis | CRH (PVN) or AVP or IL1/6 -> POMC cleaved into ACTH (10% of ant. pit.) -> CORT (half-life 1 hour; measure early morning or pharmaco-stimulate) & DHEA-S (long half life, used as CORT surrogate). CORT -> hepatic glucose release & inhibits gut Ca absorption. |
| HPG Axis | GnRH (decapapeptide, ARC)-> G-protein R-> LH & FSH (10% of ant. pit.) ->E2 & T (1 hour half life). Inhibited by: Stress/starvation/opiates, CORT, Inhibin A/B (GnRH & FSH), sex hormones (GnRH & LH). Measure LH/FSH/T in morning single measure. |
| Which cells make Inhibin B? | Sertoli/Granulosa Cells, inhibits FSH secretion |
| GnRH Pulsatility | GnRH neurons inactive before puberty. 1st pulsatility during sleep. Constant GnRH -> downregulates receptor ->infertility (treatment for endometriosis/prostate cancer/precocious puberty). Rhythm dampened in elderly. |
| PRL axis | (25% ant. pit.) No feedback inhibition. Chronic inhibition by DA. Stimulated weakly by TRH, E2, nipple stimulation. Chronic low PRL production. Single randomly-timed measure OK. |
| Post. Pit. | SON, PVN = magnocellular neurons (OXT, AVP released as precursors) distinct cells, but both types found in both nuclei. Hormones cleaved & activated in secretory vesicles |
| AVP | secreted by BOTH post. pit. & hypothal., binds V2 GPCR in DCT & IMCD, binds V1R in arteries -> vasoconstriction. Lowers body temp, increases memory, increases ACTH w/acute stress. |
| Oxytocin | nipple touch, vaginal stim -> OXT -> milk let down & myometrium contraction, kidney & vascular actions like AVP, amnesia, maternal behavior. |
| % of diet that must be donated to growth | 2-13% |
| Ways to assess growth | 1)Weight & Height/Age, 2)Growth Velocity/Age, 3)Weight kg/(Height m^2) per Age (BMI), 4)Height Age (Age @ which height =50th percentile, 5)Weight Age (Age @ which weight = 50th percentile) 6)"Bone Age"(x-ray left hand epiphyses. correlates w/pubery onset) |
| When do Pubertal Growth Spurts occur in boys vs. girls? | MALE: Age 13-14, 7-12 cm/year. FEMALE: Age 11-12, < 10 cm/year. |
| Growth Pattern | Variable before 3 years old. After 3, healthy kids follow same percentile for height until puberty. |
| Mid-Parental Target Height | = (Summed Parents' Heights -5")/2. (- for girls, + for boys). stdev = +/- 4". |
| Gene mutations leading to short stature | 1) any GH related genes, 2) PIT-1/PROP1 txn factors for GH expression, 3) SHOX (e.g. Turner's Syndrome), 4) IGF & IGFR |
| GH Axis | Somatostatin inhibits, GHRH/ghrelin/sex hormones stimulate-> GH (pulsatile; self-inhibitory; 50% of ant. pit.; 15 min half life)-> GHBP-bound-> liver IGF-1 & IGFBP3 (1/2 life = days, nonpulsatile = surrogate)-> feedback inhibition. TH= permissive. |
| GH actions | 1) required for normal adult height, 2) free FA release from adipocytes, 3) insulin resistance (inhibits glucose metabolism) in muscle & adipocytes -> prevents hypoglycemia, esp. in newborns |
| GH pulsatility | 7-8 pulses/24 hours in prepubertal male. Max. pulse amplitude w/in 1 hour of deep sleep onset. At puberty, pulse amplitude increases. |
| Somatomedin Hypothesis | =main role of GH is to regulate systemic IGF1. GH binding to R recruits JAK2 kinase -> STAT5 -> IGF-1 production. BUT locally produced IGF1 is major effector of GH. |
| IGFs | insulin-like growth factors stimulate glucose uptake in fat & muscle, 50% aa similarity to insulin (retain C-chain), stimulate collagen synthesis into cartilage. Circulate bound to BP's (e.g. IGFBP3 = major carrier). |
| IGF1 | impt't for adult growth, hepatic origin + local paracrine secretion, not found in growth plates. |
| IGF2 | impt't for fetal growth, binds insulin R -> hypoglycemia. paracrine. paternal imprinted. |
| T3/T4 actions | permissive for GH secretion. Direct stimulation of epiphyseal cartilage growth. |
| Sex Hormones & Growth | 1) enhance GH & IGF-1 secretion, 2) high levels @ puberty contribute to growth spurt, 3) E2 -> epiphyseal fusion |
| Breast Development | stimulated by E2, 1st sign of puberty followed by pubic hair stimulated by Testosterone. 1 Prepubertal, 2 Breast Bud, 3 Further Enlargement, 4 Areolar Projection, 5 Mature. |
| Penis Development | androgen-stimulated, 6 months later than female breasts. 1 Prepubertal, 2 Enlargement (red scrotum, testes), 3 Enlargement (long penis), 4 Enlargement (penis breadth & glans, dark scrotum), 5 Maturity |
| Familial Short Stature (normal variant) | at least one parent below 5th percentile -> child below 5th %. Normal birth weight, normal growth velocity, bone age, and pubertal timing. |
| Constitutional Growth Delay (normal variant) | =Late Bloomer Syndrome. usually boys. late puberty + continued growth until late, normal growth velocity. bone age delayed along w/delay in puberty. |
| Adrenal Development | Mesoderm-> adrenal primordium by 8th gestational week: Fetal Zone expresses Cyp17 & makes DHEA-S. outer Definitive Zone doesn't express Cyp17. Chromaffin cells from neural crest migrate in & form discrete islands until 1 week afer birth -> medulla. |
| Fetal Adrenal Gland | Fetal Zone makes Cyp17 & DHEA-S as precursor for placental E2 & androgens, disappears @ 1 year old, when Definitive Zone develops into Adrenal Cx |
| Adrenal blood flow | most CO/g weight of any organ, flow from Cx to medulla |
| Which enzymes are expressed in each adrenal Cx zone? | G: 21-Hydroxylase, Aldo Synthase. F: 17/21/11-hydroxylases, 3) R: 17-hydroxylase |
| ACTH stimulates: | CORT (Zona fasciculata), DHEA & Androstenedione (Zona reticularis) |
| Aldo | AngII or high [K]-> GPCR on zona glomerulosa -> Aldo |
| What are the acute and delayed/chronic effects of ACTH? | 1) Acute (sec-min) cholesterol in outer Mt membrane-> [StAR]-> inner Mt membrane Cyp11A. 2) Chronic (hours) ACTH induces "trophic action" gene expression of P450's. |
| Cholesterol Sources for Adrenocortical cells | 1) uptake from blood lipoproteins, 2) HMG CoA Reductase de novo synthesis, 3) Cholesterol Ester Hydrolase hydrolysis of cholesterol esters. |
| mineralicorticoid receptor (MR) | same affinities for CORT & Aldo. 11-beta-HSD type 2 expressed in Aldo-responsive tissues converts CORT to inactive cortisone |
| Biological FX of glucocorticoids | 1) mobilize aa's from muscle/fat 2) adipocyte lipolysis, 3) liver gluconeogenesis & glyocgenolysis, 4) catecholamine R expression in heart, 5) CNS effects, 6) inhibit immune system (NKkB & AP1) |
| hypotensive patients who do not respond to volume repletion & pressors: | May have Adrenal Insufficiency (CORT -> increased Epi & NE expression in heart) |
| 11-beta hydroxysteroid dehydrogenase Type 1 (11-beta-HSD Type 1) | converts inactive corticosteroids prednisone/cortisone into active prednisolone & cortisol in liver & adipocytes |
| Epi production in adrenal chromaffin cells: | Tyrosine [TH, rate-limiting]-> DOPA [aromatic aa decarboxylase]-> DA [DA beta hydroxylase]-> NorEpi 20% [PNMT] -> Epi 80%. stored in granules & released rapidly when sympathetics signal acute stress. Epi half life = sec-min |
| alpha adrenergic R | vasoconstriction, iris opening, GI relaxation, Sphincter tightening, Pilomotor contraction |
| beta adrenergic R | beta 1: high HR & contractility, lipolysis. beta 2: vaso- & broncho-dilation, uterus relaxation, glycogenolysis, bladder relaxation |
| Termination of Catecholamine Action | 1) desensitization & internalization of R, 2) presynaptic Epi reuptake (neurons only), 3) MAO & COMT in liver |
| Cretinism | deaf-mute retardation, pyramidal disturbance w/extrapyramidal dysfunction. Abnormal gait or di/paraplegic. Low IQ. Due to low/no TH in pregnant mom. |
| TH effects on human health | 1) TH -> proper growth. Low levels = delayed growth. 2) TH in adult: elevates basal metabolism & increases O2 consumption via Na/K ATPase -> increased glucose/FA/protein consumption |
| Hyperthyroidism | hyperphagia w/weight loss, tremors, heat intolerance, anxiety, frequent poos. |
| Hypothyroidism | Fatigue/Cold Intolerance/Weight Gain/Dry Skin/Coarse Hair/Brittle Fingernails/Irregular Menstruation/Myalgia/Constipation/ Cognitive Dysfunction. Primary = thyroid, 2ndary = Pituitary, Tertiary = Hypothalamus dysfunction. |
| Thyroid Nodules | 50% of people have them, >95% benign, high colloid content. If cancerous: Growing, large, men/children mostly who were treated w/XRT drugs. |
| Iodine absorption -> Colloid | Iodine-> Iodide in gut-> blood-> IODIDE TRAPPING: follicular cell apical NIS imports I- -> basal pendrin transporter -> colloid |
| Iodine Organification | iodination of thyroglobulin (Tg) in colloid + H2O2 from NADPHoxidase -> Thyroid Peroxidase (TPO) oxidizes I & attaches it to Y residue on thyroglobulin ->3-MIT/DIT |
| Iodine Coupling | Thyroid Peroxidase adds MIT+DIT->T3 or 2xDIT->T. Thyroglobulin attached to T3/T4 is stored in colloid. Pinocytosed into follicular cell, endosome adds to lysosome-> Cathepsins digests -> T3/4 released to blood & Tg pieces recycled |
| How is Thyroid Hormone transported in the blood? | 1) TBG carries 60-70% of T3/4. TTR (transthyretin) carries 15%. Albumin carries remaining. 0.1% TH free (accessible to target tissues). |
| Thyroid Hormone Actions | T3 enters cells directly. Deiodinases I & II convert T4 to active T3. T3 binds TR-RXR heterodimer -> binds TRE's on DNA -> expression. |
| What molecular effects does TSH signaling have? | 1) more NIS, TPO, Tg, H2O2, 2) Tg proteolysis by cathepsins & pinocytosis, 3) follicular cell mitosis. |
| reasons for high bone age | may appear more advanced w/high T3, E2, CORT, Testosterone. |
| Equation for BMI using lb & inches | weight lb/(height in.^2) x 703 |
| BMI at risk for adult obesity | > 85th percentile for high BMI |
| What are the pubic hair stages? | 1 (no hair) -> 5. Timing correlates with genitalia & secondary sexual features development. Driven by androgens. |
| What is the largest endocrine organ in the body? | GI tract |
| What type of hormonal interaction is it where 2 hormones together -> double the effects? | Additive |
| What type of hormonal interaction is it where 2 hormones together give > 2x the effects? | Synergistic |
| What type of hormonal interaction requires 2 different hormones for a 1x effect? | Complementary (e.g. FSH + testosterone needed for sperm development) |
| What type of hormonal interaction requires 1 hormone so that a cell can be receptive to another hormone? | Permissive (e.g. E2 at the uterus induces expression of P4 receptors) |
| What type of hormonal interaction is it where 1 hormone opposes the effects of another hormone? | Antagonistic (e.g. insulin induces fat formation whereas glucagon induces fat breakdown. insulin represses glucagon release) |
| What are the classes of hydrophilic hormones? | Proteins >100 aa's long. Peptides < 100 aa's long. Amines = 1 aa derivative. |
| What are the classes of lipophilic hormones? | Unbroken B ring (cholesterol-derived). Broken B ring (vitamin D-derived). Thyroid Hormone (iodide confers hydrophobicity). |
| What is the level of regulation of protein/peptide hormones? | at the level of secretion. typically synthesized in advance and stored until ready to be released. Preprohormone synthesized in ER, refined in Golgi -> Prohormone -> active hormone (still inside cell) -> secretory vesicles. |
| What is a Prehormone? | hormones secreted in an inactive state, and are later activated by the target cell. e.g. T4 is inactive in circulation, converted to active T3 @ target cell. |
| At what stage is steroid hormone production regulated? | at the level of de novo synthesis. immediate release (no reservoirs). |
| What is the GH diurnal rhythm & the best time to measure GH? | episodic peaks evey 3 hours (greatest levels @ night). Use IGF1 as a proxy. |
| What is one peptide hormone that circulates with a carrier protein? | IGF circulates with IGFBP3 |
| What is the Priming Effect? | when 1 hormone increases the number of receptors for another hormone on a target cell, a greater response is seen (e.g. GnRH on the ant. pit.) |
| What is a mechanism to prevent desensitization of a target cell to its hormone? | Pulsatile Secretion (may prevent downregulation of receptors on target cell) |
| radioimmunoassay (RIA) | add labeled hormone to sample serum + single Ab (recognize 4 aa's). competition b/tw hormones @ Ab. measures amount, but doesn't distinguish free from carrier-bound hormones). Ab's may not recognize all forms of hormone. |
| ELISAs | broader linear range, shorter incubations, fewer reagents & measurements, don't need radioactivity. 2 Ab's required (2 diff sites of hormone), 1 bound to petri dish, 1 free. Does not measure hormone activity/active vs. bound hormone. |
| What is the first thing that would happen if you cut the pituitary stalk? | Prolactin levels go sky high -- no more DA to inhibit it! |
| What are the hypothalamic nuclei supplying the posterior pituitary? | PVN, SON |
| What is cancer of Thyroid C cells called? | Medullary Thyroid Cancer |
| What happens if someone has Thyroid Hormone deficiency at different stages of life? | 1) baby -> CNS cretinism. 2) child -> bone malformation. 3) adult -> metabolism disorder. |
| What is NIS? | The Na-Iodide Symporter on the apical membrane of follicular cells of the thyroid. Involved in Iodide trapping |
| What is the % composition of thyroid hormone? | T4 (70%). T3 = 30%. Deiodinases in target tissues converts T4 into T3. |
| How does the body increase heat production using thyroid signaling? | TRH production is increased (T3 burns fuel to generate heat) |
| Frequency of disorders of sexual development | 1 in 100 |
| What is sex reversal? | When sexual phenotype does not correlate with sex chromosome complement. e.g. SRY on otherwise normal X chromosome causes sex reversal in XX individuals. |
| Which genes are critical for male spermiogenesis but not sexual differentiation? | DAZ & AZF. (SRY is needed for male fertility but not for spermiogenesis specifically). |
| Which gene is located adjacent to PAR1 on the Y chromosome? | SRY. Can be translocated to X chromosome with abnormal crossover. key gene for testis development. Gene product "bends" DNA. |
| What is SRY gene product? | DNA binding protein of High Mobility Group (HMG) family. Conserved across species. Mutations cluster iN HMG region. Never been shown specifically to activate transcription via promoter region. Activated in pre-Sertoli cells very early in development. |
| What is SF1 important for? | jump-starts sexual development. MALES: Sertoli Cells make AMH, SRY ->SOX9 in testes-> FGF9 & male feed-forward. FEMALES: Ovaries make Wnt4 & beta-catenin inhibit SOX9. |
| 45X female development | initially generate normal number of follicles, but by birth, all have degenerated. Oocyte critical for ovarian development (constitutive pathway of sexual differentiation). |
| What is a cause of pseudohermaphrotism leading to both male and female internal genitalia? | Mutation in AMH in males |
| Which hormones stimulate Leydig vs. Sertoli cells? | LH -> Leydig -> Testosterone & Androstenedione. FSH -> Sertoli cells -> AMH (development) & inhibin (puberty). |
| What do the Mullerian ducts form? | Fallopian tubes, uterus, upper vagina. |
| How does Testosterone signal during development? | Acts locally at HIGH concentration for Testicular & Wolffian development. If not enough testosterone from one side -> unilateral development. DHT production is NOT unilateral (except maybe testicular descent). |
| What is AMH? | Antimullerian Hormone, TGF-beta family, signals via Smads to initiate apoptosis, acts locally. mutations = persistent Mullerian Duct Syndrome. |
| When does fusion of the uterine tube occur? | @ 9 weeks. First, elongation of Mullerian tubes, then fusion, then canalation & resorption of intermediate tissue. |
| What is equivalent to the penile shaft in the female? | labia minora |
| When can you tell when a fetus is male vs. female? | Male can tell several weeks early (@ 7 weeks development b/c of DHT), ovaries appear @ 12 weeks. but cannot tell if abnormal sexual development until birth. |
| Do female embryos make estrogen? | YES, but not critical for female sexual development. May affect normally sized uterus & vagina. |
| What is the role of oocytes in sexual differentiation? | Maintain ovarian development. |
| What is affected in congenital adrenal hyperplasia? | 21 hydroxylase deficiency -> blocks up system, so precursors are made into androgens. looks male external, but no palpable mass in scrotum (ovaries do not descend) |
| AIS (androgen insensitivity) syndrome | testes makes AMH -> no Mullerian duct, externally female + vaginal pouch (lower 1/3 of vagina not from Mullerian duct). @ puberty high testosterone is converted to E2 (tall + large breasts) BUT no pubic hair. |
| What are the contents of semen? | Sperm 5-10%. 65% from seminal vesicles (fructose, coagulants, seminogelin inhibits motility until ejaculation) 30% from prostate (anticoagulants that work 15 min later). |
| Normal semen analysis | pH >7.2, volume >2 ml, [ ] >20 million/ml, motility >50% forward, morphology > 50% normal, leukocytes < 1 million/ml (if more, may have prostatitis) |
| Kruger's Sperm Infertility Analysis | > 14% morphologically normal sperm = still fertile |
| What is hyperactivation of sperm? | Increasingly circular nondirective movements of sperm as they move up the female reproductive tract (due to uterine contractions) |
| What are types of male infertility? | Obstructive: 1) absent fructose b/c seminal vesicles blocked, 2) Cystic fibrosis (no vas Deferens) 1-2%). Nonobstructive: 1) AZF & DAZ mutations, 2) Klinefelter's (severely decreased sperm production), 3) Y chromosome microdeletion mutation. |
| What are environmental requirements for normal spermatogenesis? | sperm take 3 months to develop. Tobacco, Alcohol, Marijuana BAD for 3 months prior. High Temp: Cryptorchidism, Varicocele (pampiniform plexus dilation esp. on the left-> heat). Illness: fever, mumps orchitis. |
| What are hormonal requirements for normal spermatogenesis? | 1) high local testosterone, 2) normal LH/FSH. Anabolic steroids are inhibitory (-feedback. no local testosterone production). |
| How do androgens and estrogen maintain bone health? | estrogens inhibit bone resorption & induce osteoclast apoptosis. Androgens stimulate bone cell proliferation (bone converts testosterone to estrogen also). |
| What is the pattern of male testosterone production in early life? | 1) hCG instigates T in early fetal period. 2) T increases a few days after delivery due to withdrawal of placental steroids. 3) Prolonged surge during 1st year of life. |
| HPG changes during male puberty | peaked pulsatile secretion overnight to early morning (measure early morning). at puberty, LH secretion continues throughout the day. |
| How is serum testosterone measured? | Total testosterone only measured. Free testosterone assays = expensive & not accurate. |
| What are permanent effects of T/DHT? | enlarged penis/testes, deep voice, hair growth on face & chest. |
| What are temporary effects of T/DHT? | Hematopoiesis, Libido. |
| What is the role of the fetal adrenals on androgen signaling? | DHEA & DHEA-s are very weak, but can be converted to more potent androgens. High levels in fetus (converted by fetus to estriol), adrenals involute just before birth, DHEAs decrease @ birth |
| What hormone modulates beard growth & chest hair in males? | testicular (not adrenal!) testosterone |
| What pulse frequency of GnRH stimulates FSH vs. LH? | slow GnRH pulse frequencies (q2 hours)-> FSH -> late luteal phase peak. Faster-> LH (late follicular phase peak). |
| FSH & LH surge properties in female menstrual cycle: | Surge just before luteal phase. FSH levels are higher. Due to E2 (certain amount of E2 required). 24-36 hours later = ovulation. |
| Which cells release Inhibin across the menstrual cycle? | Inhibin B made by granulosa cells (peaks just before ovulation), Inhibin A by luteal cells (peaks just before menstruation). |
| Why do some women have spotting after ovulation? | Drop in estradiol just before ovulation |
| What are the general roles of estrogen and progesterone on folliular function? | estrogen = growth factor, progesterone = stability factor |
| What is the hormone state at the selection window? | low P, low E2, higher but equivalent FSH & LH. FSH is dropping, LH is rising. Only 1 follicle survives drop in FSH. |
| What hormones are made by the ovaries | E2, P4, activin/inhibin, EGF/VEGF (respond to insulin in diabetes), Cytokines, Prostaglandins |
| Granulosa cell hormone production: | avascular = no cholesterol. **no Cyp17 enzyme (cannot make DHEA or Androstenedione) but CAN convert them to estrogens w/17betaHSD. |
| Thecal cell hormone production: | Cyp17 to make androstenedione. No 17-beta-HSD & aromatase. Well-vascularized. |
| What are the Activins? | A, B, AB. Activin R specific for activin. Made by ovary, pituitary, bone, stem cells, etc. paracrine. Stimulate FSH & augment FSH actions. |
| Describe follicular development | 1 cohort of follicles/month, starts in utero, all follicles undergo atresia before puberty b/c NO FSH!!!!, rate of growth & atresia cannot be changed by any interventions (e.g. fertility treatment just rescues follicles that would otherwise have died) |
| What is gondadotropin-independent follicular growth? | from primordial to early antral follicle (gonadotropin-dpdt occurs in late antral & requires FSH) |
| Describe a healthy dominant follicle during selection: | HIGH granulosa cell #, FSH-R's, IGF1, LH-R's, blood vessels, aromatase. "Estrogen-Dominant" |
| What are androgen dominant follicles? | LESS: granulosa cells, aromatase, IGF1. "Atretic/Apoptotic" |
| What is the function of the corona radiata for the oocyte in ovulation? | makes the oocyte sticky for attachment to fimbriae |
| How is the ovary releasead during ovulation? | inflammatory process: histamines/prostaglandins, plasminogen activator/collagenase, matrix metalloproteinases |
| What happens with regression of the corpus luteum? | PGF2alpha & P4 decline (-> menstruation), macrophages invade, apoptosis-> fibrotic corpus albicans. (rescued by beta-hCG if pregnancy) |
| What are normal Ca levels? | 2.2-2.5 mM Ca (10 mg/dL) = TIGHTLY regulated. Too much: nausea/vomiting, kidney stones, bone pain & fracture, dementia. Too little: tetanus, cardiac arrhythmia. |
| What are the 3 distribution fractions of Ca? | 1) ionized Ca++ (biologically active, 50%), 2) protein-bound eg Albumin (40%), 3) complexed as salt w/citrate or PO4 or SO4 (10%) |
| ***What are the effects of elevated albumin on Ca regulation? | Does not alter bioavailable (ionized) Ca (subtract 0.8 mg/dl from total Ca for each 1 g/dl increase in albumin. opposite for decreased albumin.) |
| how does pH affect ionized Ca amounts? | every 0.1 rise in pH decreases ionized Ca by 5% & vice versa |
| How does the GI tract handle Ca? | Absorbs 500 mg daily but secretes 300 mg daily. 600 mg lost in stool daily. |
| vitamin D as a hormone | cholesterol-derived (seco-steroid b/c broken B ring). Vitamin D activation increases when low Ca -> 1,25 dihydroxy variant = calcitriol, bioactive. -> high serum Ca. |
| Where does most bone turnover/remodeling occur? | Trabecular bone (20% of skeleton, but 75% of bone surface). 20-30% turned over annually. = Cancellous/Spongy bone. |
| When does human bone mass peak? | ~30 years old. periosteal apposition is greater in men (thickened perimeter & stronger bone -> slower loss w/age) . women show accelerated loss @ menopause. |
| What is RANK? | RANK = receptor for RANKL (similar to TNF) secreted -> pro-osteoclast differentiation. Osteoprotegerin (OPG) = RANK ANTAGONIST. M-CSF is also PRO-osteoclast differentiation. |
| What are the precursors of osteoclasts? | Mononuclear precursors from bone marrow. more RANK-L promotes osteoclast differentiation, more OPG inhibits (eventual apoptosis). |
| ***What hormone receptors do osteoclasts express? | RANK, calcitonin & estrogen |
| How do osteoclasts digest bone? | release H via V-type pump -> pH 4.5 dissolves CaPO4, also release digestive enzymes. lipids in osteoclast membrane protect it from self-digestion. minute-to-minute changes. |
| What receptors and signaling molecules do osteoblasts use? | Receptors for: calcitropic hormones, estrogen, androgen, IGF1 & TGFbeta, autocrine cytokines. Secrete: M-CSF, RANK-L, & OPG to control osteoclasts (para/juxtacrine) in response to vitamin D!! |
| What is collagen's molecular structure? | mostly Type I -> long protein w/every 3d aa = Gly. 10% Proline (causes kink). Helical. Vitamin C-dpdt post-translational modification (involved in scurvy) |
| What is bone modeling? | Changing size & shape of bone w/negligible change in mass occurring during childhood & adolescence. e.g. flared ends of bones & enlarged cranial vault. Involves bone creation & degradation. |
| What is bone remodeling? | Major activity of adult skeleton. Renews & repairs, requires gravity. |
| How is PTH synthesized & released? | soluble peptide hormone synthesized as pre-prohormone, stored in vesicles. 34 aa amino terminal = active site. |
| How is low serum Ca sensed by parathyroid glands? | GPCR senses low Ca (low signaling -> PTH release -> raises serum Ca) |
| How does PTH work on bone? | 1) binds receptor on osteoblasts -> RANK-L released -> osteoclast precursors fuse & activate. 2) stimulates osteoblast collagen production. 3) chronic high PTH can also increase osteoclast activity. |
| What is PTHrP? | PTH related peptide. overproduced in cancer -> humoral hypercalcemia of malignancy (low PTH & vitamin D but high PTHrP). not normally a player (except in developmental chondrocyte proliferation & placental/mammary gland Ca transport). |
| What are the systemic effects of calcitonin? | GPCR senses high Ca OR Gastrin signaling -> calcitonin release 1) inhibits osteoclast activity directly, 2) promotes phosphate excretion. Used to treat osteoporosis. |
| how does vitamin D signal? | lipophilic hormone, binds VDR receptor in cytoplasm, deactivated into tri-hydroxy 1,24,25-vitaminD3 (enzyme upregulated when v. high vitamin D). |
| What are the systemic effects of vitamin D? | 1) increases osteoblast secretion of RANK-L & osteocalcin2) stimulates calbindin in kidney. 3) promotes Ca & PO absorption in GI tract. Good for treating bone disease secondary to kidney failure, or hypoparathyroidism. |
| How does thyroid hormone alter bone growth? | increases bone resorption & turnover |
| How does CORT alter bone growth? | pharmacologic doses stimulate bone resorption & inhibit bone formation, impair Ca resorption from GI |
| How does E2 alter bone growth? | Inhibits osteoclasts. @ menopause, more bone is absorbed. androgens stimulate |
| What are some common disorders affecting ovarian function? | precocious/delayed puberty, abnormal uterine bleeding, polycystic ovaries, premature ovary failure |
| What is the average age of menarche? | 12.5 years |
| What is the normal range of menstrual period invervals? | 21-35 days (always 14 days after ovulation) |
| What is the simple pathway for cholesterol generation of steroid hormones? | C27 chol -> C21 pregnane (adrenals, ovary/testes, placenta) -> C21 CORT (adrenals) or -> C19 androgens (adrenals, ov/test) -> C18 estrogens (ov/test, placenta) |
| what are the roles of LH & FSH on granulosa cells? | LH 1) stimulates FSH-R on granulosa cells & 2) increases cAMP in theca & granulosa cells -> ovulation-specific gene expression. FSH in granulosa cells 1) more FSH/LH R's, 2) IGF1 produced (anti-apoptotic), 3) mitosis, 4) increased aromatase activity. |
| What is the role of LH on thecal cells? | LH -> androgen production (precursor for E2 in granulosa cells) |
| When does oocyte number peak? | ~24 weeks of gestation (6 month old embryo) |
| When does oogonia number peak? | ~18 weeks of gestation (just prior to oocyte peak) |
| What hormonal changes cause menstruation? | Degeneration of the corpus luteum -> simultaneously low E2 & P4 |
| Which circulating fuels are soluble? | glucose, lactate, free FA's, kentones, aa's. |
| Which circulating fuels are insoluble? | TAG's (chylomicrons or VLDL) |
| Which hormones increase/decrease serum glucose? | RAISES: Glucagon. LOWERS: insulin. Epi, CORT, GH also alter circulating gluc. |
| Why can't muscles release glucose to the bloodstream? | Lack the glucose-6-Phosphatase enzyme that converts glucose to a form that can be transported across the membrane. Muscle breaks down glycogen, but keeps the energy for itself. |
| How are the subunits of insulin linked together? | A and B chains are covalently linked via disulfide bonds. Peptide hormone. |
| How is insulin made? | Pre-proinsulin -> proinsulin -> insulin+C-peptide -> packed into granules |
| How much secreted insulin is cleared via first pass through the liver? | 50% . Insulin has a v. short half-life. C-peptide is a better marker of insulin SECRETION. |
| Which tissues primarily increase glucose uptake with insulin signaling? | muscle & adipocytes (also reduces release of free FA's from adipocytes by inhibiting lipolysis). Increases glucose utilization & inhibits FA oxidation. |
| What is the molecular action of insulin signaling? | decreases cAMP-> dephosphorylation-> decreased glycogenolysis, increased glycolysis and glycogenesis. 3-C pyruvate fragments increase malonyl CoA activity -> Lipogenesis (packaged as VLDL by liver). Ketone synthesis is decreased (low FA utilization). |
| What is the molecular structure & synthesis of glucagon? | 29 aa peptide hormone cleaved from 180 aa proglucagon protein (that also contains GLP-1). Glucagon v. difficult to measure (unstable) |
| How does glucagon signaling occur? | increases cAMP -> PKA (opposite effects as insulin). Glucagon receptors are ONLY found in liver & adipose tissue (NOT in muscle) |
| What regulates glycogen production/break-down? | PKA (glucagon) activates glycogen phosphorylase kinase -> activates glycogen phosphorylase -> Glycogen break-down. PKA (glucagon) inhibits glycogen synthase. Glucose directly inhibits phosphorylase. |
| Where is the glucagon receptor located? | adipocytes and liver cells (NOT MUSCLE) |
| How does glucagon regulate adipocyte fat break-down? | PKA (glucagon) activates Hormone-Sensitive Lipase (increases TAG breakdown to free FA's & glycerol -> bloodstream). |
| Which hormones modulate the activity of hormone sensitive lipase? | Epi & Glucagon ACTIVATE. Insulin & Adenosine INHIBIT. |
| What signaling pathway causes ketone body production for energy? | Glucagon: inhibits acetyl CoA Carboxylase required to make Malonyl-CoA -> CPT1 released from inhibition -> long chain FA's enter Mt to be broken down to ketones. Insulin: excess Malonyl CoA -> lipogenesis. |
| what is the densest soluble fuel that can circulate in the blood and feed the brain? | Ketone Bodies |
| How is glucose sensed? | There is no direct receptor, changes in glucose metabolism is measured via ATP: ADP ratio. ATP-sensitive K channel SUR1 closes, coupled to a v-gated Ca channel (Kir6.2) that allows granules to release contents. |
| Where is Glut2 expressed? | Beta pancreatic cells, and Liver. Very low affinity but high capacity for glucose uptake. Glucokinase also expressed in these locations. |
| What happens to glucose when it enters a cell? | Rapidly P'ated to trap it in the cell. e.g. Hexokinase 4 ("Glucokinase") |
| What does SUR1 channel stand for? | Sulfonyl Urea channels (affected by antidiabetic drugs targeting that channel) |
| What is contained in insulin secretory vesicles of beta pancreatic cells? | insulin, C-peptide, zinc |
| What transcription factors are upregulated by glucose/insulin in liver cells? | ChREBP (glucose) and SREBP-1c (insulin). Both promote conversion of excess glucose to FA's by increasing appropriate enzyme expression. |
| In which cells does insulin cause GLUT4 translocation to the membrane? | muscle, adipose. |
| *** How do catecholamines affect brain availability of glucose? | alpha/beta adrenergic R -> increased glucagon production. alpha R -> decreased insulin release. Epi/NorEpi released during exercise. |
| What are the 4 types of diabetes? | Type I (autoimmune against beta islet cells), Type II (insulin resistance), Gestational (5% pregnancies, transient but confers risk for Type II), MODY genetic type (abnormal beta cell development/fxn). |
| How does a severe Type 2 diabetic secrete insulin in response to glucose? | Resembles a Type I diabetic (low release) |
| How do GI tract enteroendocrine cells sense nutrients to release hormones? | GPCR's, metabolic cues of ATP:ADP, "Taste-Receptors", ion channels, neural signals. Effector = high intracellular Ca++. Juxta/Para/Endocrine signaling. |
| How is a preprohormone converted to an active hormone? | Pre directs protein to appropriate organelle, then Pre is cleaved -> Pro-hormone -> Proprotein convertases (PC1/3 or 2) cleave -> mature hormone |
| What is a prehormone? | e.g. T4 or cholecalciferol (vitamin D3 precursor): Secreted, then activated ONLY in the target organ. |
| Gastrin | 3 forms, promotes acid secretion & calcitonin release, made by G-cells in Antrum, inhibited by low pH |
| CCK | stimulates gallbladder contraction, many forms, made & secreted by I cells in duodenum. prohormone cleaved by PC1/3. Stimulated by fats/proteins. |
| Which 2 digestive hormones share the same receptor? | Gastrin (antral stomach G cells) & CCK (s.i. I cells). CCK-1 receptor prefers CCK. CCK-2 receptor binds more gastrin (higher concentration in that area). |
| PYY | (colon/rectum L cells) Has a tyrosine (Y) @ each end. MAY BE an incretin, increase tissue sensitivity to insulin, & induce satiety. Stimulated by fat, released in 15 min (too soon for direct fat sensors). |
| Which hormones are deactivated by DPPIV | DPPIV cleaves (in blood stream) PYY and GLP-1 -> inactivation |
| Which GI hormones are released in the colon? | PYY and GLP-1 |
| Secretin | (S cells) related to glucagon, 27 aa's. stimulated by acid in the duodenum. Stimulates release of biliary water and bicarbonate from pancreas. |
| What condition is associated with secretin deficiency? | Achlorohydria (inability to produce gastric acid). |
| What is the half-life of GI hormones? | V. short. usually less than 10 minutes. Gastrin (?) = 40 minutes. |
| What is the "incretin effect"? | difference in insulin secretion b/tw amount glucose given orally (absorbed) and given IV (injected). Nutrients -> incretins -> increased insulin & C-peptide release. |
| What are inclusion criteria for incretin status? | 1) must be released in response to glucose. 2) must reach sufficient physiological levels to increase insulin release @ beta cells. |
| Which hormones are incretins? | GLP-1 and GIP. increase insulin release (only work when glucose is high). NOT secretagogues = cannot generate hypoglycemic state. |
| Which incretin is ineffective in diabetics? | GIP (glucoinsulinotropic peptide) |
| GIP | (K-cells in duodenum/jejunum). PC1 cleaves 42 aa hormone from pro-hormone. First 2 aa's cleaved by DPPIV -> inactivation in blood stream -- 20 min 1/2 life. v. low plasma [ ], max by 15 min. Stimulated x fat, carbs, nutrasweet, rapid gastric emptying. |
| Where are GIP R's located? | brain, GI tract, islet cells, pituitary, heart, adrenal gland & adipose tissue. |
| What happens when GIP receptor is knocked out in mice? | Glucose Intolerance! (GLP-1 receptor k/o also glucose intolerant, but more mild phenotype) |
| GLP-1 | 30 aa's (PC1/3) from PROGLUCAGON. L cells. stimulated x dietary carbs, nutrasweet, fat, & protein, plasma FA's, rapid gastric emptying. BIPHASIC (peak @ 15 min, prolonged peak @ 1 hr). Degraded by DPPIV (3 min 1/2-life) |
| What is the synthesis difference between glucagon and GLP-1 | PC2 cleaves glucagon in alpha cells. PC1/3 cleaves GLP-1 in L cells. |
| What are GLP1-R signaling effects? | 1) increased insulin release, 2) decreased liver glucose release, 3) increased beta cell proliferation & mass! 4) satiety, lowers food intake, memory, learning. (Gx -> cAMP _> PKA) |
| What links Gila Monsters to GLP-1? | Exendin 4 (Gila monster salivary GLP-1) cannot be cleaved by DPPIV enzyme -> 30 minute halflife (instead of 3 min). Synthetic version = Exenatide (injected) |
| What is Exenatide? | "Byetta". Adjuvant protein therapy with other anti-diabetic agents. Must be injected. Reduces plasma glucose, causes slight weight loss, improves insulin secretion. BUT nausea, diarrhea, vomiting (altered gut bolus transit time), immune reaction. |
| What is Liraglutide? | GLP mimetic with half-life of 11-15 hours. C16 FA is attached that binds albumin -> increases GLP-1 levels 40x. Injected. |
| What are the DPPIV inhibitors? | Januvia (Sitagliptin), Galvus (Vildagliptin). Improved oral glucose test, prevents diet-induced obesity, more modest fx than GLP-1 mimetics. oral. 8-14 hr half-life, cleared x kidney. only 3x change in GLP-1 levels. cons: UTI's. |
| Where is DPPIV expressed? | membrane-bound to capillaries of kidney & intestine. |
| What is Vildagliptin? | (Galvus) DPPIV antagonist, broken down x liver & excreted x kidneys. |
| What are the major metabolic characteristics of ob/ob & db/db mice? | hyperphagic, increased adiposity, high insulin, hyperglycemic. |
| What is the mutation in the ob vs. db mouse? | ob k/o = no leptin. db k/o = no leptin R. |
| What does leptin do? | DECREASES: body weight, intra-abdominal fat, insulin, food intake. INCREASES: glucose uptake by liver (lowers blood sugar). |
| What cell type does leptin bind to? | Leptin is a hormone released by white adipose tissues. Leptin: 1) inhibits NPY/AgRP/GABA neuron. 2) activates POMC/CART neuron (same ObRb receptor for each) |
| What do NPY/AgRP neurons do? | NPY activates NPY-R (opposite effects to leptin), AgRP inhibits MC4R (leptin effects), GABA inhibits POMC/CART neurons (leptin effects) |
| what is POMC? | large pro-protein that can be cleaved to form alpha MSH (melanocortin) ->binds MC4R -> anorexigenic. stimulated x leptin |
| What do MC4R-expressing neurons do? | DECREASE: food intake, intra-abdominal fat, insulin sensitivity. INCREASE energy expenditure. Constitutive activity. MSH = agonist for MC4R, AgRP = competitive antagonist/inverse agonist (eliminates ALL activity). |
| Which signals alter POMC/CART neuron activity? | AGONIST: Leptin, 5HT. ANTAGONIST: GABA. |
| How is Ghrelin activated? | Synthesized x P/D1 enteroendocrine cells (stomach & duodenum), post-translational modification. |
| What does Ghrelin do? | 1) increases GH release. 2) Hunger & feeding (GH-independent). 3) Decreases energy expenditure (measured by O2 use). |
| What is an effective means to decrease ghrelin release? | Gastric Bypass Surgery |
| In which brain regions is the Ghrelin Receptor (GHSR) expressed? | Arcuate nucleus, hippocampus, vTA (reward, ventral tegmental area). |
| Which mutations cause obesity? | ob, db (common in people), MC4R (2.5% of obese individuals have mutation), POMC. Leptin RESISTANCE also occurs. |
| What happens if GHSR mutated? | (Ghrelin Receptor) -> cachexia & low body weight. |
| What is a normal adult BMI? | 18.5-24.9 (overweight = 25-29.9) |
| Why is adipocyte fat storage effective? | No water necessary, low-volume, high-density TAG's. (e.g. glycogen needs water = high vol. only 4 cal/g) |
| How much energy is contained in TAG's? | 9 kcal/g (most dense fuel available) |
| What happens when excess lipids invade non-adipocyte tissues? | insulin resistance, hepatic steatosis, lipotoxicity of beta cells, maybe also cardiomyocytes. |
| What types of fat are protective against diabetes? | subcutaneous fat (women have more than men), pear-shaped fat deposition. |
| What is required for adipocyte development? | PPAR-gamma nuclear hormone receptor. ligand = free FA derivative. |
| Which drugs are PPAR-gamma agonists? | Actos, Avandia (thiazolidinedione antidiabetic drugs). Adipocytes take up free FA's & spare muscle & liver from steatosis. |
| How do white vs. brown adipocytes differentiate? | White from fibroblasts, brown from primordial muscle cells. |
| Why are brown adipocytes brown? | Lots of mitochondria (contain iron) |
| What stimulates brown adipocyte heat production? | Norepi from central neurons -> beta adrenergic receptor on brown adipocyte -> heat production instead of ATP production (uncoupled mitochondrial oxidative phosphorylation) |
| What are some examples of lipodystrophy? | 1) PPAR-gamma mutation (familial partial lipodystrophy), 2) Congenital generalized lipodystrophy, 3) Acquired (HIV-associated) -> adipose wasting + lipids stored instead in muscle/liver, insulin resistance, hyperglycemia, low leptin/adiponectin. |
| What is the difference between small and large mature adipocytes? | Small release mostly adiponectin, v. insulin-sensitive. Large adipocytes release mostly leptin. |
| What is the structure of adiponectin? | Protein hormone w/highly coiled collagen-like region + globular domain. Circulates as high MW multimer @ HIGH concentrations. Stimulated by PPAR-gamma. |
| What is the difference in adiponectin between a lean & obese individual? | LEAN: more adiponectin, mostly high MW (also pre-menopausal women). OBESE: less adiponectin, mostly low MW (post-menopausal women + men). |
| How does adiponectin signal? | DECREASES glucose production, intracellular TAG's, hepatic insulin resistance, muscle cell glucose uptake. |
| What happens to adiponectin in diabetics? | 1) high in Type I, 2) low in Type II diabetes |
| Why is sleep apnea associated with obesity? | Fat in neck accumulates w/obesity, compresses airways -> difficulty breathing (lose weight in neck & face & liver first) |
| What are good candidate traits for bariatric surgery? | BMI >40 or BMI >35 with health complications |
| What was the problem with jejuno-ileal bypass? | Calcium Oxalate Kidney Stones (Oxalate absorbed in GI b/c fat binds Ca), Migratory Polyarthritis (bacteria), Protein-Calorie Malnutrition, Liver Failure -> High Mortality Rate (from bacterial toxins) |
| Early Bariatric Surgery | Remove vagal input, dissect out antrum, hook up fundus to duodenum/jejunum -> intractible weight loss. |
| Gastric Bypass Surgery | Bring limb of small intestine-> top of stomach, staple off intermediate areas. chemoreceptors in distal ileum sense food sooner -> satiety signaling in brain. |
| Dumping Syndrome after Gastric Bypass | cramps, diarrhea, flushing, tachydardia, diaphoresis (sweating), syncope. sudden water loss in intestines (early: due to hyperosmolar contents in intestines -> sympathetic response). late: hypoglycemia due to HIGH insulin (GLP-1) |
| What is Nesidioblastosis? | Hyperproliferation of pancreatic islets |
| What is Pernicious Anemia after Gastric Bypass? | Intrinsic Factor (Fe) & B12 deficiency |
| What does the glucose tolerance test measure? | OGTT (oral glucose) measures how quickly glucose is cleared from the blood (measured via blood draws) |
| How much glucose does the brain require per hour? | 6 g/hour (requires 50-60 mg/dL glucose in the arteries) |
| What conditions alter binding globulin concentrations? | 1) liver disease/viral hepatitis (low/high TBG), 2) pregnancy/birth control/E2 (high TBG & SHBG), 3) Obesity (low SHBG), 4) aging (high SHBG), 5) testosterone (low SHBG) |
| What does it mean if someone has normal PTH levels and hypercalcemia? | Hyperparathyroidism |
| What are the "hormone pairs" that should be included when measuring sex steroids? What about TSH? | E2 with FSH. T with LH. TSH with T4. |
| When should hormones be measured in urine instead of plasma? | 1) Cushing's (24H CORT). 2) Pheochromocytoma (24H Epi/NorEpi because short burst type secretion) |
| Which hormones are released from the PVN? | CRH, TRH, Somatostatin |
| Which hormones are released from the ARC? | GnRH, GHRH, DA |
| What disease should be tested for if a person has hyperprolactinemia? | Primary hypothyroidism. Measure TSH levels to see if they are high (release from tonic feedback inhibition). TRH stimulates both TSH and PRL. |
| What % of cells in the ant. pit. is made up of each hormone-type? | 10% ACTH, 10% FSH/LH, 15% TSH, 25% PRL, 50% GH |
| How are OXT & AVP stored before release? | preprohormone is stored in vesicles. enzymes in vesicles cleave & convert to prohormone + Neurophysins (chaperones). |
| Where are AVP receptors located? | V2 receptors in renal CD. V1 receptors in blood vessel smooth muscle (shunts blood toward core body) require much higher [AVP]. |
| Which organs grow the most between infancy and adulthood? | Muscles > Bones > Heart > Skin/liver/kidney > Brain |
| At what bone age are boys vs. girls about to start puberty? | Bone age (relative maturation of epiphyses) = 12 for Boys, 10 for Girls. |
| Which GH action counteracts the Somatomedin Hypothesis? | GH-induced insulin resistance of fat & muscle cells is NOT mediated by IGF-1 |
| What are IGFII actions? | Paracrine. Acts through IGFIR & Insulin R -> prenatal growth. |
| What is the first committed step in CORT steroidogenesis? | Cyp11A enzyme acts on cholesterol |
| What happens when there is Persistent ACTH deficiency? | Adrenal atrophy & 2ndary adrenal insufficiency (inability to respond to exogenously applied ACTH) |
| Why is CORT called "Glucose Sparing"? | It frees up FA's & aa's for energy so that glucose can preferably be used by the brain. |
| What is the action of Type I 11-beta-hydroxysteroid dehydrogenase? | It is expressed in liver & adipose to convert inactive corticosteroids (prednisone/cortisone) into active prednisolone & cortisol. |
| How is NorEpi production by enterochromaffin cells regulated? | Sympathetic Splanchnic signaling -> Tyrosine Hydroxylase activation (1st step in Epi production). CORT activates PNMT (final step converts NE to Epi) |
| What converts iodide to iodine in the thyroid follicle? | Thyroid Peroxidase (TPO; uses H2O2 from NADPH oxidase) |
| What adds iodine to MIT & DIT? | Thyroid Peroxidase TPO |
| What is the subcellular localization of Cyp17? | Endoplasmic Reticulum |
| What is the female counterpart to peritubular myoid in males? | Interstitium. |
| Which structures form from the Wolffian Duct? | Testosterone stimulates development of: Epidydimis, Vas Deferens, Seminal Vesicles, Prostate. |
| What structures form from the embryonic Genital Tubercle? | Glans Penis or Clitoris |
| What structures form from the embryonic Genital Fold? | Penile Shaft or Labia Minora |
| What structures develop from the embryonic Genital Swellings? | Scrotum or Labia Majora |
| What structures develop from the Urogenital Sinus? | Prostate and Bulbourethral Glands or Lower Vagina & Skene's Glands [NOTE: upper vagina comes from mullerian duct!] |
| What organelles are missing from mature sperm? | ribosomes, rER, Golgi, nucleolus |
| Which hormones does aromatase work on? | Testosterone and Androstenedione -> estrogen and estrone. [DHT cannot be converted!] |
| Which enzyme converts testosterone to DHT? | 5-alpha-reductase |
| Which enzymes can deactivate testosterone and DHT? | 1) 17-beta-HSD-Type2 (works on T better than on DHT), 2) 3-alpha-HSD, 3) Liver Cyp450 |
| ***How is testosterone carried in circulation? | 60-70% w/SHBG (inactive), 40% w/albumin & other proteins (bioactive), 1% free |
| How does LH increase Leydig cell testosterone production? | ACUTE: LH signaling activates StAR. LONG-TERM: LH -> steroidogenic enzyme expression in Leydig Cells. |
| What other hormone binds the LH receptor in the fetus? | hCG in males -> early testosterone production (LH takes over @ end of 1st trimester) |
| What brings about adrenarche? | @ 8 years of age, zona reticularis expands & makes DHEA-S -> pubic hair in boys & girls. Independent of HPG axis. |
| What causes the preovulatory decline in FSH levels? | high levels of Inhibin B and E2 (E2 -> granulosa cells now express LH receptors) |
| What signaling molecule causes vasospasm of spiral arterioles leading to menstruation? | PGF2-alpha |
| How do RANK, OPG, and M-CSF modulate osteoclast differentiation & activity? | RANK: 1) precursor differentiation, 2) precursor fusion & activation, 3) increased activity, 4) anti-apoptosis. OPG: does the exact opposite. M-CSF: only promotes precursor differentiation. |
| How are minerals transported from the site of osteoclast activity to the blood? | Osteocytes carry them in long processes |
| What molecules are stored in bone aside from CaPO4? | Collagen, Acidic Glycoproteins, P-proteins, Osteocalcin, Growth Factors |
| Which factors promote bone degradation during remodeling? | IL1, M-CSF, G-CSF, TNF, TGFalpha, T3, CORT |
| Which factors promote bone formation during remodeling? | BMPs, PDGF, IGF1/2 (autocrine), TGFbeta. |
| What stimulates/inhibits vitamin D production? | PTH, low calcium and low PO4 stimulate. autoinhibition. |
| What are the systemic effects of incretins (GIP & GLP1)? | 1) inhibit gastric acid secretion & GI motility, 2) locomotor activity, neurogenesis, satiety, 3) adipocyte glucose uptake & lipogenesis (GIP only) |
| What happens to GIP & insulin levels when a high fat 0 carb diet is consumed? | GIP is stimulated by fat, but insulin is not released b/c GIP is NOT a secretagogue. |
| Which incretin has no effects on Type II Diabetics? | GIP. NO longer a commercial drug target. |
| What cells does GLP-1 signal to? | beta islet cells, muscle, liver, fat, brain (hypothalamus) |
| What happens to ghrelin levels when dieting? | INCREASE |
Created by:
rbxbrown