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Intro to Endocrine

Introduction to Endocrine Physiology

How far of a distance does the endocrine system travel? Long distance communication system
What are the chemical messengers of the endocrine system? Hormones
Where are the hormones secreted from? Endocrine glands
What are endocrine glands? Ductless glands that secrete hormones into the blood
How are exocrine glands different from endcrine? Possess ducts and secrete into body cavities or body surfaces
What are the main endocrine glands of the endocrine system? Pineal, hypothalamus, pituitary, thyroid, parathyroid, thymus, adrenal, pancreas, ovary, and testis
What are similarities between the endocrine and nervous system? Both use chemical messengers
Compare the chemical messengers of the endocrine and nervous system Nervous system - neurotransmitters. Endocrine - hormones. Both - bind receptors for a response
What are the differences between the endocrine and nervous system? NTs only travel a short distance across the synapse. Hormones released into blood and therefore travel long distances
What are are examples of short-distance communication by chemical mediators? Autocrine and paracrine
How does an autocrine communicate? Signal acts on the same cell that released it
What are examples of autocrine cells? Il-1
How does a paracrine communicate? Signal released by one cell acts on cells nearby
What are examples of paracrine cells? TGF-beta and FGF
How is there specificity in autocrine and paracrine cells? Rely on target cell receptors for specificity
How can endocrines be controlled? Brain and some independency of brain
How does the brain control endocrine glands? Can establish time-based patterns of hormone secretion, can respond to homeostatic imbalances and modulate hormone secretion to address them, can secrete hormones in response to stress, other psychologic factor
What is an example of establishing time-based patterns for hormone secretion? Changes in hormone secretion that depend on time of day or month or even season in some species - i.e. menstruation
What is an example of responding to homeostatic imbalances and modulate hormone secretion to address them? Too much sodium in blood? Structures in brain will detect that and increase ADH secretion → increased water retention → "dilution" of the sodium in blood
How can endocrine control act independently of the brain? Responding to homeostatic imbalances by themselves
What is an example of endocrine control independent of brain? Parathyroids can regulate calcium concentration without neuro input
Explain CNS control o the endocrine system Hormone synthesis and secretion fro the hypothalamus is initially controlled by other parts of the CNS - many tracts communicate with the hypothalamus
What is the function of the hypothalamus, with respect to the endocrine system? Stimulate or inhibit hormone synthesis and/or secretion in the pituitary
What are the different control classifications? Hormonal control, humoral control, neural control
Explain the hormonal control of the endocrine system Controlled by the CNS as well as feedback from other hormones
What is an example of hormonal control? Control of the pituitary by hypothalamic hormone secretion
Explain humoral control of the endocrine system Usually independent of the CNS control, the endocrine gland autonomously senses and responds to the homeostatic imbalance
What is an example of humoral control? Parathyroid glands are controlled by the concentration of Ca in capillary blood
Explain neutral control Refers to endocrine control by the autonomic nervous system
What is an example of neural control? Adrenal medulla is controlled by sympathetic nerve
What kind of control for corticotropin-releasing hormone? Hormonal
Explain the hormonal control of corticotropin-releasing hormone Hypothalamus releases CRH → CRH travels through blood to the anterior pituitary → CRH causes anterior pituitary cells to release ACTH into bloodstream → ACTH travels to the adrenal glands and causes cortisol release
What are trophic hormones? Those that act on other endocrine glands
What are non-trophic hormones Those that act on target cells
What are examples of a trophic hormone? CRH and ACTH
What are examples of a non-trophic hormone? Cortisol
What are the three types of endocrine gland stimuli? Hormonal - hypothalamus. Humoral - capillary blood contains concentration of Ca, which stimulates PTH. Neural - preganglionic SNS fiber stimulates adrenal medulla cell
How is specificity established with hormones? By specificity of the receptors - hormones can only bind to receptors with the correct specificity and will therefore only affect tissues expressing those receptors
Describe the size and population of hormonal receptors on a target cell Receptors are large proteins and target cells usually have 2000-100,000 receptors
Where is the pituitary gland located? Sits in sphenoid cavity - sella turcica
What is the pituitary gland connected to? Hypothalamus via a hypophyseal/pituitary stalk (or infindibulum)
What are the two lobes of the pituitary gland? Anterior pituitary (adenohypophysis) and posterior pituitary (neurohypophysis)
What does the anterior pituitary contain and why? Glandular tissue to produce and secretes many hormones
What does the posterior pituitary contain and why? Neural tissue to store and secrete two hormones produced by hypothalamus
Where does the anterior pituitary gland originate from? Originates frmo Rathke's pouch
What is the anterior pituitary gland derived from? Ectoderm - upward growth of primitive oral cavity
What is the origin of the posterior pituitary gland? Because it is an outgrowth of the brain, it has neural origin - outpouching of the third ventricle
What are the 3 components of the anterior lobe? Pars distalis, pars intermedia, pars tuberalis
What is the pars distalis? Part of anterior pituitary lobe - glandular tissue involved in production and secretion of hormones
What is the Pars intermedia? Part of anterior pituitary lobe - separates anterior and posterior lobes
What is the pars tuberalis? Covers stalk attaching to the hypothalamus
What are acidophils? Somatotrophs which produce growth hormones and lactotrophs which produce prolactin
What are basophils? Thyrotrophs → thyroid stimulating hormone. Gonadotrophs → GSH, LH. Corticotrophs → ACTH
What are chromophobes? Cells have minimal or no hormonal content
How can a chromophobe have minimal or no hormonal content? May be degranulated acidophils or basophils (depleted of hormones) or be stem cells that have not yet differentiated into hormone-producing cells
What is the pituitary population of corticotrophs? 15-20%
What is the product of corticotrophs? ACTH
What is the target of corticotrophs? Adrenal gland
What is the pituitary population of thyrotrophs? 3-5%
What is the product of thyrotrophs? TSH
What is the target of thyrotrophs? Thyroid gland
What is the pituitary population of gonadotroph? 10-15%
What is the product of gonadotrophs? LH, FSH
What is the target of gonadotrophs? Gonads
What is the pituitary population of somatotrophs? 40-50%
What is the product of somatotrophs? GH
What is the target of somatotrophs? All tissues, liver
What is the pituitary population of lactotrophs? 10-15%
What is the product of lactotrophs? PRL
What is the target of lactotrophs? Breasts, gonads
What cell type has the highest pituitary population in anterior pituitary? Somatotrophs
What is the structure of releasing/inhibiting hormones from the hypothalamus? Tends to be small peptides
What is the structure of LH, FSH, TSH? Glycoprotein hormones
What is the structure of GH, PRL, ACTH? Non-glycoprotein hormones
What is ACTH considered a peptide? Only 39 AAs long
What are the three classifications of hormones, based on structure? Proteins/peptides, steroids, amines
What are proteins? Long polymers of AAs
What are peptides? Short chains of AAs
What are amines? Tyrosine derivatives - thyroid hormones, catecholamines
What are examples of steroids? Aldosterone, cortisol, estradiol, progesterone, testosterone, vitamin D
What is another name for vitamin D? Cholecalciferol
What are examples of amines? Thyroxine (T4), triiodothyronine (T3), catecholamines (epinephrine, norepinephrine)
What are examples of polypeptides? ACTH, angiotensin, calcitonin, glucagon, GH, insulin, MSH, ADH, oxytocin
What are examples of glycoproteins? GSH, hCG, LH, TSH
What is the most predominant type of hormone structure in the body? Peptide/protein
What is the range in size for peptides/protein? Few as 3 AAs to almost 200 AAs
What hormones are only 3 AAs? Thyrotropin-releasing hormone
What hormones are 200 AAs? GH, PRL
How many AAs are in a protein? 100 or more
How many AAs are in a peptide Fewer than 100
What kind of hormones are GH, TSH, ADH, insulin, and oxytocin? Protein/peptide
How are protein/peptide hormones produced? Synthesized as preprohormones or prehormones, cotranslated in RER, packaged into secretory vesicles in Golgi and stored in cytoplasm until release
What are steroids produced from? Cholesterol
How is the production of steroids increased? Upregulate LDL receptors and increase side-chain cleavage enzyme activity
Why are LDL receptors upregulated to increase production of steroids? Because LDL carries cholesterol
Why is side-chain cleavage enzyme activity increased? To make steroids by converting cholesterol which starts with side-chain cleavage enzyme activity → increased production or activity
How is a specific type of steroid hormone produced? Depending on type of enzymes present in each target gland cell
Why are carrier proteins needed? Increases half life and acts as a reservoir
What hormones are carrier proteins especially important for? Hydrophobic hormones
What are examples of hydrophobic hormones? Testosterone, estrogen, progesterone, thyroid hormone, adrenal steroids,
What carrier protein does testosterone, estrogen, progesterone bind to? Sex hormone binding globulin
What carrier protein does thyroid hormone bind to? Thyroid binding globulin
What carrier protein does adrenal steroids bind to? Transcortin mostly
Is albumin an example of a carrier protein? Yes, it can act as a carrier protein by binding to hydrophobic hormones
What other hormones have carrier proteins, besides hydrophobic hormones? GH and IGF
What is a short-loop feedback? Pituitary hormone providing negative feedback to hypothalamus, inhibiting secretion of the releasing hormone
What is an example of a short-loop feedback? GHRH from hypothalamus is inhibited by GH that has been released from pituitary
What is a long-loop feedback? Released from peripheral endocrine glands inhibiting pituitary and/or hypothalamic secretion of releasing hormones
What is an example of long-loop feedback? IGF1 stimulated by GH. IGF1 inhibits GHRH and GH secretion by long loop feedback
What is the function of a feedback loop? Modulate basic rhythm of hormone secretion
What are hormones with clear cycles? GH, TSH, ACTH, LH, GSH, melatonin
What are gonads? Testes in male, ovaries in female
What hormones does GnRH regulate? Secretion of both LH and FSH
Explain the role of LH and FSH in males LH causes testosterone release from the testes, FSH causes inhibin release from the testes
Explain the role of LH and FSH in females LH and FSH act on the ovaries to produce both estrogens and progestins. FSH causes production of inhibin
What are androgens? Group of hormones that play a role in male traits and reproductive activity (spermatogenesis)
What are examples of androgens? Testosterone, dihydrotestosterone
What are estrogens? Group of hormones that play a role in sexual and reproductive development, especially in women.
What role does estrogen play in the reproductive development in women? Development of ovarian follicles and oocytes; thickening of the uterine lining to prepare for pregnancy
What is progesterone? Hormone that plays a role in menstrual cycle, pregnancy, and embryogenesis
How does progesterone help in pregnancy? Maintenance of uterine lining to allow pregnancy
What is inhibin? Feedback hormone whose main target is the pituitary
What is a primary endocrine disorder? When the target gland is not functioning properly
What are target glands for the major hormones of the adenohypophysis? Adrenals, thyroid, gonads, breasts, liver, other tissues
What is a secondary endocrine disorder? Anterior pituitary problem
What is a tertiary endocrine disorder Hypothalamic problem
What is hypothyroidism? Decreased thyroid hormone
In a primary hypothyroidism, what would be the problem and what is the implication? Thyroid is the problem so it's not a problem with the levels of TSH but that the target gland can't produce hormones to give feedback inhibition → TSH levels would be increased
In secondary hypothyroidism, what would be the problem and what is the implication? Anterior pituitary issue so unable to produce TSH → TSH levels would be decreased
In tertiary hypothyroidism, what would be the problem and what is the implication? Hypothalamic problem so unable to produce TRH to stimulate release of TSH → TSH levels would be decreased
What is hyperthyroidism? Increased thyroid hormone
In Grave's disease, antibodies mimic action of TSH, what is the implication of this? Antibodies are able to bind to the receptors which causes thyroid to release the hormones (T3/T4), giving feedback inhibition → TSH levels would decreased
What are hypothalamic hormones that act on prolactin? Prolactin Release Hormone (PRH), Prolactin Inhibiting Hormone (PIH), and Thyroid Release Hormone
What is PIH also known as? Dopamine
What does anterior pituitary hormone acts on the breast? Prolactin
What hypothalamic hormone acts on thyroid stimulating hormone? Thyroid Releasing Hormone (TRH)
What anterior pituitary hormone acts on the thyroid gland and what is the implication? TSH acts on thyroid gland to release thyroid hormones which acts on many tissues
What hypothalamic acts on adrenocorticotropin hormone (ACTH)? Corticotropin release hormone (CRH)
What is the implication of the release of ACTH? Acts on adrenal cortex to release cortisol which acts on many tissues
What hypothalamic hormones act on the growth hormone? Growth hormone release hormone (GHRH) and growth hormone inhibiting hormone (GHIH)
What is growth hormone inhibiting hormone (GHIH) also known as? Somatostatin
What anterior pituitary gland acts on the liver? GH acts on liver to releases insulin-growth factor 1 which acts on many tissues
Does GH only act on liver? No, it can act on many tissues
What anterior pituitary hormones does gonadotropin release hormone act on? Follicle stimulating hormone and luteinizing hormone
What are FSH and LH are known as? Gonadotropins
What does gonadotropins act on and what is the implication? Endocrine cells of the gonads to stimulate androgens, estrogens, and/or progesterone which can on many tissues and germ cells of the gonads
What is a hypophyseal portal system? System of blood vessels in circulation at base of brain connecting hypothalamus and anterior pituitary that function in the transport and exchange between the hypothalamic arcuate nucleus and anterior pituitary gland
What is the structure of the hypophyseal portal system? Originates from superior hypophysesal artery which branches off to form the primary plexus of capillaries that supplies blood to the median eminence which drains into hypophyseal portal veins into a secondary plexus to drain into circulation
Explain the path of releasing/inhibiting hormones in the portal system Hypothalamus secretes releasing/inhibiting hormone and travels through primary capillary plexus then penetrates the median eminence to portal veins which carry them to anterior pituitary
Explain the path of anterior pituitary hormones in the portal system After receiving input from hypothalamus, hormones produced by anterior pituitary enter a secondary capillary plexus and from there, drain into circulation
How does posterior pituitary hormone section differ from anterior hormone portal system? Posterior is neural tissue and is an extension of the neurons in the paraventricular and supraoptic nuclei of the hypothalamus. Cell bodies of these regions rest in hypothalamus and axons descends and ends in axon terminals in the posterior pituitary
Where is GHRH released from? Hypothalamus - probably arcuate nucleus
What secondary messenger, important in many biological processes, is elevated by GHRH cAMP when GHRH acts on the receptor in the anterior pituitary
What is the cycle of GHRH release? Released in pulses, mostly during sleep (amplitude of pulses change from minute to minute)
What is released from the stomach in response to fasting? Ghrelin
What is the function of ghrelin? Hunger hormone - stimulates appetite, increases food intake, promotes fat storage
What role does ghrelin play on GH? Increases GH secretion
What kind of hormone is ghrelin? Peptide hormone - 28 AAs
What hormone is released from adipose tissue? Leptin
What is the function of leptin? Regulates energy balance by inhibiting hunger
What role does leptin have on GH? Increases GH secretion
Where is somatostatin released from? Pericentricular area of the hypothalamus
What is the function of somatostatin? Decreases cAMP in the somatotrophs → decreases GH release. Modulating effect of GHRH on somatotrophs
What positively controls GH release? GHRH, ghrelin, and other stimulatory factors
How many AAs are in GHRH? 43
How are pre-pro-hormones formed? Cell transcribes 5 exons to form GH messenger RNA to either 22-kDA protein or 20-kDA protein. Alternative splicing in 3rd exon results in two isoforms in pituitary. They are translated in RER and enter secretory pathway
How is mature GHs formed? Pre-pro-hormone cleaved into pro-hormone. Cleavage of pro-hormone and disulfide bond formation results in mature GH in Golgi
What happens after mature GHs are formed? Stored in secretory vesicles until GHRH stimulates release
What can also stimulate new synthesis of GH? GHRH
What role does age have on GH release? Varies greatly with age. Children secrete almost 100X more than elderly
Where does majority of GH secretion occur in? 70% occurs with the onset ofslow-wave sleep
Cell transcribes to form two different isoforms of GH: 22kDA and 20kDA, what does it translate to? 191 AA or 176 AA protein hormone, respectively
What tissues has GH been identified in? Muscles, fat, bone/cartilage, kidney, liver, brain, pancreas
What kind of cell signaling does GH act on? Tyrosine-kinase associated receptor
What is the critical step in initiating GH signaling JAK2 activation
How is JAK2 activated? One GH binds to two GH receptor → dimer undergoes rotation to bring together two intracellular domains each of which bind to one JAK2 molecule
What happens after JAK2 is activated Induces cross phosphorylation of Tyr residues in the kinase domaine of each JAK2 molecule follwed by Tyr phosphorylation of GH receptors
How is the intracellular signaling cascade triggered? Phosphorylation residues on GH receptors and JAK2 form docking sites for different signaling molecules - STATS
What are the acute affects of GH? Stimulates lipolysis, inhibits glucose uptake, and stimulate gluconeogenesis (hepatocytes, kidneys)
How quickly can the acute effects of GH be seen? Minutes to hours
Why are the acute effects of GH called diabetogenic? Because they oppose the action of insulin
In acute conditions, what is a potent stimulator of GH secretion? Hypoglycemia - effect is independent of insulin, glucagon, and epinephrine
In acute conditions, does a decrease in protein have stimulatory effects on GH secretion? Yes, but less potent as blood sugar
In chronic conditions, what is growth hormone secretion linked to? Degree of cellular protein depletion instead of degree of glucose insufficiency
What effect does GH have on lipids? Lipolytic - activates hormone sensitive lipase and inhibits lipoprotein lipase
How can GH be ketogenic? Creates acetyl CoA → ketone bodies in liver
How can insulin abolish lipolytic effects of GH? It promotes absorption of sugar from blood to fat which is antagonistic to lipolysis
How does the hyperglycemic effect of GH compare to glucagon and epinephrine? GH is mild compared to glucagon and epinephrine
What effect does GH have on insulin? Decreases insulin sensitivity on skeletal muscle and adipose tissue, increased gluconeogenesis in liver, required for normal pancreatic insulin release
How does GH decrease insulin sensitivity? Antagonizes insulin action because it is diabetogenic
What role does insulin have on gluconeogenesis in the liver? It decreases gluconeogenesis by increasing glucose intake
What is the result of insulin activity for glucose? Less glucose in blood
Since GH is stimulated by hypoglycemia, how does it increase blood glucose in the liver? Increased FA oxidation → increased acetyl CoA needed for gluconeogenesis
What is gluconeogenesis? Synthesis of glucose from noncarbohydrate precursors such as lactate and alanine
How does GH help regulate normal pancreatic insulin release Excess GH leads to hyperglycemia so pancreatic beta cells releases insulin to absorb sugar from blood to lower blood sugar
What are the long-term effects on GH, with respect to insulin growth factors? Target tissues are induced to produce IGF
What are IGFs also known as? Somatomedins
Are the acute effects of GH mediated by insulin growth factors? No
What are the target tissues of GH in respect to IGF? Liver, muscle, cartilage, bone, kidneys
What kind of signaling does IGF work as? Paracrine fashion
What are the effects of IGF? Mild insulin effects (hypoglycemic) - weakly bind to insulin receptors - poor stimulation of glycogenesis
What are the long term effects of GH besides IGF? Linear growth of bones, increased skeletal muscle mass, decreased size of fat stores (increased lean muscle mass)
How does GH help with linear growth of bones? Hyperplasia of chondrocytes in the epiphyseal plates, leading to increases in height and increased AA uptake
How does GH help increase skeletal muscle mass? Increased AA uptake and protein catabolism; and hyperplasia
What are other hormones that increase growth? Glucocorticoids, thyroid hormone, cortisol, androgens, estrogens, progesterones, and more
What is important for sleep regulation? GHRH
What stage of sleep does GHRH help induce? Stage 4 deep sleep, non-REM sleep
What is the implication of GHRH and the stage of sleep that it is inducing? Growth during deep stage 4 of sleep are closely related
GHRH can also be secreted locally as a paracrine hormone, what is the implication of this? Influence blood vessel and parenchymal cell growth in these tissues
What does GH and IGF both bind to? Carrier proteins
Do all GH and IGFs bind to carrier protein? No, but over 90% of IGFs do. Less for GH
What is the implication of binding to a carrier protein? Increase half life to allow longer term effects
GH binds less tightly to carrier protein, what is the implication of this? Half life (20 minutes) much less than that for IGF1/IGF2 which is 2 hours
What is prolactin made by? Lactotrophs of anterior pituitary
What is prolactin? 199 AA single chain polypeptide - similar structure to GH and hPL
What is prolactin regulated by? PRH and PIH (dopamine)
What is the half life of prolactin? Unbound - short - 20 minutes
What kind of cell signaling does prolactin activate when it binds to its receptor? Tyrosine kinase
What secretes milk in a lactating breast Alveolar cells
How does milk fill the ducts in each alveoli? Myo-epithelial cells squeeze alveoli to express milk into ducts
How is milk secreted from alveolar cells? Combined merocrine and apocrine secretion
What is mammogenesis? Mammary gland growth and development
What role does prolactin have on mammogenesis? Induces mammogenesis - which is important to maintain mammary gland tissue after baby is born
What is lactogenesis? Milk production
What role does estrogen and progesterone have on lactogenesis? Estrogen - stimulates growth of duct cells. Progesterone - stimulates growth of milk producing cells in the glands
What role does prolactin have on lactogenesis? After pregnancy, estrogen and progesterone levels drop, prolactin stimulates production of proteins and lactose for baby's nutritional needs
What is galactopoiesis? Continual production of milk (not initiation)
What is the major stimulator for PRL release? Suckling
What are non-mammary gland actions of PRL Inhibit GnRH, fetal growth stimulator
How can PRL inhibit GnRH release? Alteration of the normal pulses leads to decreased LH and FSH levels → anovulation and amenorrhea. Important after women delivers baby and is still breast feeding
How does PRL affect fetal growth? Via increased IGF-2 production
What are inhibitors of PRL Somatostatin
What are stimulators of PRL? Glucagon, TRH, estrogen but are minor compared to dopamine and suckling
Created by: nnguyen44



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