ENDOCRINE PHYSIOLOGY BRS OUTLINE
IP3 Mech
 all the “Releasing Hormones”
except CRH
 hormones assoc with posterior
pituitary
 AngII
 Alpha-1 receptors
cAMP Mech
 all hormones assoc with anterior
pituitary
 the exceptions: CRH, ADH (V2)
 Calcium regulating hormones: PTH,
Calcitonin
 Beta-Receptors
 Other: Glucagon, HCG
Which Hormones have “Releasing Hormones”
 TRH, CRH, GnRH, GHRH
 Only anterior pituitary hormones—all except for prolactin and MSH
Hormone Structure Relationships
1. TSH, LH, FSH—identical α subunits
2. POMCACTH, MSH, β-endorphin
3. somatotropin, prolatin—analogs
Growth Hormone
 GH Actions
o Diabetogenic—↓Glc uptake into cells
o ↑muscle mass
o ↑fat breakdown/lipolysis
o Make IGF
 GHRH stimulates secretion
 Somatostatin inhibits secretion
 Negative feedback control (GH stim somatostatin)
 Excess GH—Tx with Octreotide (somatostatin analog)
Prolactin
Inhibits GnRH secretion (thus inhibit FSH, LH); (Body’s like: “dude you JUST got pregnant, you don’t want to get prego
again that soon”, so body doesn’t let you while you’re still breast feeding)
ADH
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V1 receptor—vasoconstricion
V2 receptorinsert aquaporin/AQP2reabsorb H2O at kidney principal cells
Oxytocin
 Oxytocin actions
o Milk ejection of breasts
o Uterine contraction during labor
 Can be given to induce labor and reduce postpartum bleeding
Thyroid gland
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Peroxidase inhibited by propylthiouracil—used in Tx of hyperthyroidism to stop thyroid hormone production
Wolff-Chaikoff Effect = High levels of I- inhibit organificationinhibit thyroid hormone production
T3 & T4 carried in blood by TBG (thyroid binding globulin)
Thyroid hormone up-regulates β1 receptors in the heartβ-blocker used in therapy of hyperthyroidism too
Overall thyroid hormone effect is catabolic
Increase in HR, SV, CO, RR
Adrenal Gland
 “G-F-R” & “It gets sweeter as you get deeper” but exceptionCorticosterone (some mineralcorticoid
activity/aldosterone prescursor) is made in the Zona Reticularis with the sex androgens.
 Synthesis of the Hormones
o Add –OH at C-21 (21-OH)lead to mineralcorticoid production
o Add –OH at C-17 (17-OH)lead to glucocorticoid production
 19-C steroids = Androgenic activity (in testes, androstenedionetestosterone)
 18-C steroids = Estrogenic activity (Aromatization occurs in ovaries/placenta to make estrogen)
Glucocorticoid
 Leaves peak right when you wake up (8am) and drop to lowest before you go to bed (midnight)
 CRH made in paraventricular nucleus
 ACTH stimulates hormone synthesis of ALL zones of adrenal cortex
o stimulate CholesterolPregnenolone via cholesterol desmolase
 Cortisol negative feedback—inhibits CRH release, inhibits ACTH release etc
o Dexamethasone suppression test

Actions
o ⊕ Gluconeogenesis
 ↑ protein breakdown (—AA goes into gluconeogenesis pathway)
 ↓Glc utilization and insulin sensitivity of adipose tissue
 ↑ fat breakdown/lipolysis (—glycerol goes into gluconeogenesis pathway)
o Anti-inflammatory/Immune Suppression
 ⊕ lipocortininhib PLA2 (no more arachidonic acid to make PG’s & LTs)
 Inhibit IL-2 productioninhib T-cell proliferation
 Inhibit Histamine & Serotonin release from mast cells
o Maintain Vascular Integrity
 Up-regulate α1-receptors (vasoconstriction)
Aldosterone
 Stimulated by low blood volume (via RAAS) & Hyperkalemia
 Actions
o ↑ renal Na+ uptake—principal cells DCT & CT
o ↑ renal K+ secretion—principal cells DCT & CT
o ↑ renal H+ secretion—α-intercalated cells DCT & CT
Pathophysiology of Adrenal Cortex—Diseases
Addison’s Disease = Primary adrenocortical insufficiency
Most commonly due to autoimmune destruction of adrenal cortex and causes acute adrenal crisis
Cause
Symptoms
↓Glucocorticoid/Cortisol
Hypoglycemia, weight loss, weakness
↓Androgen
Less pubic/axillary hair in women
↓Mineralcorticoid/Aldosterone
ECF volume contraction, hyperkalemia, metabolic acidosis, hypotension
↑ACTH
Low cortisol levels no longer inhibiting ACTH release
Hyperpigmentation: ↑ACTH so ↑POMC (precursor) which also makes ↑MSH
Secondary Adrenocorticoid Deficiency
Primary deficiency of ACTH
Symptoms similar to Addison’s but does not have hyperpigmentation and Aldosterone levels are normal
Cushing’s Syndrome = Adrenocortical Excess
 Most commonly drug-induced/exogenous glucocorticoids
 Primary Hyperplasia of Adrenal Glands
 (Cushing’s Disease when due to overproduction of ACTH)
Cause
Symptom
↑cortisol
Hyperglycemia, ↑protein catabolism (muscle wasting), central obesity, moon facies, buffalo
hump, poor wound healing, hypertension, osteoporosis (cortisol causes increased bone
resorption), Striae
↑Androgen
Virilization and menstrual disorders in women
Treatment = Ketoconazole (inhib of steroid hormone synthesis) can be used to treat Cushing’s Disease
Metyrapone:
Conn’s Syndrome = Hyperaldosteronism
Caused by aldosterone secreting tumor
Symptom
Explanation
Hypertension
Increase Na+ reabsorption leading to increase in ECF volume and blood volume
Hypokalemia
Increases K+ secretion
Metabolic Alkalosis
Aldosterone increases H+ secretion by distal tubule, increasing “new” HCO3 reabsorption.
↓renin secretion
ECF & blood volume negative feedback and inhibit renin
21β-Hydroxylase deficiency = an Adrenogenital Syndrome
 ↓ Cortisol & Aldosterone levels
o ↑ACTH (bc decrease cortisol feedback levels)
o Metabolic alkalosis,
 ↑Androgens & ↑urinary 17-ketosteroids
o Virilization in women, early pubic hair, suppression of gonadal function in men and women
17α-hydroxylase deficiency
 ↓Glucocorticoid & Androgen levels: hypoglycemia, less pubic/armpit hair in women
 ↑mineralcorticoid levels: metabolic alkalosis, hypokalemia, hypertension
 ↑ACTH (bc low cortisol)
PANCREAS
 Islets of Langerhans contain 3 cell types: α, β, and delta cells
o Rapid cell-to-cell communication via gap junctions and portal blood supply that bathes alpha and delta
cells in blood from beta cells (containing insulin)
Signaling Mechanism
Stimulus for
secretion
(incomplete list but good
enough)
Inhibit Secretion
Actions
Effect on Blood
levels
Insulin
Tyrosine kinase receptor
↑Glc
↑AA
↑FFA
Glucagon
GH
Cortisol
GIP
ACh
↓Glc
NE, EPI
Somatostatin
↑Glc Uptake
↑ Glycogen synthesis
↓Gluconeogenesis
↑ Glycogenolysis
↑Fat uptake/deposition
↓Lipolysis
↑ Protein synthesis
↑ K+ uptake into cells
↓ [Glc]
↓ [FFA], ↓[ketoacid]
↓ [AA]
Hypokalemia
Glucagon
cAMP mechanism
↓Glc
↑AA
CCK
NE, EPI
ACh
↑Glc
Insulin
Somatostatin
FFA, Ketoacids
↑ Gluconeogenesis (⊖PFK)
↑ Glycogenolysis
↑ Lipolysis (by ⊖FA synth), ↑Ketoacid
↑ [Glc]
↑ [FFA], ↑[ketoacid]
Glucagon
 It ⊕Gluconeogenesis by ⊖PFK enzyme of glycolysis
 It ⊕Lipid breakdown by ⊖FA synthesis
 It causes increased urea production bc it causes AA’s to be used for gluconeogenesis, and their leftover amino
groups are made into urea
Insulin = Anabolic
 Synthesis
o Proinsulin is synthesized as one chain. Once in the storage granules, it cleaves off the C-peptide fragment.
[C-peptide] is used to monitor βcell function
 Insulin downregulates its own receptors, so the number of receptors is ↑ in starvation and ↓in obesity
 It ⊖Gluconeogenesis by ⊕PFK
 It ⊖Ketoacid formation bc it ↓FA degredation (lipolysis) which provides less Acetyl CoA substrate for ketoacid
formation
CALCIUM, PTH, VIT D PHYSIOLOGY
PTH
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Made by Chief cells of parathyroid glands
Secretion
o Controlled by Ca2+-sensing Receptors: low Ca2+ causes less binding to the receptor and increases PTH
secretion
o Mild drops in [Mg2+] can stimulate PTH secretion
o Severe drop in [Mg2+] inhibits PTH secretionproduces symptoms of Hypoparathyroidism (hypocalcemia
etc)
Actions
Main Overall Effect: ↑[Ca2+] & ↓[Phosphate] in serum
o Increase Bone Resorption
 See ↑urinary Hydroxyproline excretion
o Increase Phosphate excretion (via Inhibit Phosphate reabsorption at Proximal Tubule)
 See ↑urinary cAMP (cAMP is byproduct of PTH’s action at PT)
o Increase Ca2+ reabsorption at Distal Tubule
o Increase Ca2+ absorption in GI tract (via Stimulating active VitD formation in kidney)
High PTH: gets rid of Phosphate so you see phosphate in urine
Low PTH: Phosphate no longer controlled so it gets really high in serum and is no longer excreted
Pathophysiology of PTH
Disease State
Primary Hyperparathyroidism
Humoral Hypercalcemia of
Malignancy
Hypoparathyroidism
Albright’s Hereditary Dystrophy
(Pseudohypoparathyroidism)
Renal Osteodystrophy
& Osteomalacia
Cause
↑PTH from parathyroid
adenoma
Ca2+/Phos
Hypercalcemia
↓Phos
↑Phos excretion
*Characteristics
↑urinary Ca2+ (overload)
↑urinary cAMP
↑PTH-related peptide
from tumor
Hypercalcemia
↓Phos
↑Phos excretion
Hypocalcemia
↑Phos
↓Phos excretion
Hypocalcemia
↑Phos
↓Phos excretion
Hypocalcemia (from no
VitD and from Phos
binding)
↑Phos
↓Phos excretion (bc of
GFR)
↓PTH (feedback inhibition
from high Ca2+ levels)
Surgical removal or
congenital
Defective Gs protein
inkideny and bone = end
organ resistance to PTH
From Chronic Renal Failure
1. Kidney not making
enough active VitD
2. Kidney not excreting
enough phosphate
(↓GFR—less Phos
filtered—phos retention)
Tetany
↑ PTH (from the low Ca2+)
Levels are not corrected by
giving patient PTH
↑PTH (2o)
Too much Bone Resorption
(from PTH)
↓VitD
Familial Hypocalciuric
Hypercalcemia (FHH)
Ca2+ Sensing Receptor
mutation (inactivating)
↑Ca2+
↓Ca2+ excretion
Vitamin D
 Active form = 1,25-dihydroxycholecalciferol
 Inactive forms = Cholecalciferol, 25-hydroxycholecalciferol, 24,25-dihydroxycholecalciferol
 1α-hydroxylase—catalyzes the production of active form of Vit D
o Enz is stimulated: ↓[Ca2+] & [Phos]; ↑PTH
 Vit D Actions
 Main overall action is to ↑Ca2+ and ↑Phos; and mineralize new bone
o Increase Ca2+ absorption at GI—via Vit D dependent Calbindin in enterocytes
o Increase Phosphate absorption at GI
o Increase renal reabsorption of both Ca2+ and Phos
o Increases bone resorption—providing Ca2+ & Phos to mineralize “new” bone
Calcitonin
 Made by Parafollicular (C-cells) of Thyroid
 Secretion stimulated by ↑Ca2+
 Inhibits bone resorption
 Used to treat hypercalcemia