Post on 03-Jan-2016
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Some Definitions I
Endocrine: glandular secretion of substances inside the body
Exocrine: glandular secretion of substances outside the body (sweat gland, liver, pancreas)
The endocrine system uses hormones to convey information through the bloodstream
Hormone: a substance released by an endocrine gland and transported through the bloodstream to another tissue (target) where it exerts its function (stimulatory or inhibitory)
Autocrine: the hormone acts on the cell that has produced it(insulin)
Paracrine: the hormone acts locally on nearby cells (sex steroids in the ovary)
Some Definitions II
The endocrine glands
Several glands located in different areas of the body
Ductless (do not have a duct system)
Richly vascularized
“Classic” Endocrine Glands
Anterior Hypophysis ACTH, TSH, LH, FSH, GH, PRL
Posterior Hypophysis Oxytocin and ADH
Thyroid T4, T3 and calcitonin
Parathyroid PTH
Adrenal Cortex Aldosteron, Cortisol, DHEA et al.
Adrenal Medulla Epinephrine and Norepinephrine
Testis Testosterone, Inhibin
Ovary Estradiol, androgens
Pancreatic Islets Insulin, glucagon, somatostatin, etc
Placenta hCG, hPL, estradiol, progesterone
“Non-classic” Endocrine Glands
Brain CRH, TRH, GnRH, dopamine, GHRH, somatostatin
Heart Atrial natriuretic peptide
Kidney Renin, 1,25-Vit. D, erythropoietin
Liver Insulin-like growth factor-1
Stomach Gastrin
Small intestine Many regulatory peptides
Chemical Nature of Hormones
•Derived from one amino acid (tyrosine):
•amine: dopamine, norepinephrine, epinephrine
•thyroid hormones: T4 and T3
•Polypeptides:
•some are small (TRH is 3 AA)
•some are big (GH is ~200 AA)
•Steroid hormones (derived from cholesterol):
•with intact steroid nucleus (gonadal and adrenal)
•with broken steroid nucleus (vitamin D)
Amine
Thyroid Hormones
Peptides & Steroids Hormones
Functions of Hormones
Reproduction and Sex
•Ex: LH, FSH, PRL, E2 and T
Growth
•Ex: GH, insulin-like growth factors
Maintenance of water, electrolyte & blood pressure:
•ADH water
•Aldosterone Na and K
•PTH, Vit. D, calcitonin calcium and phosphate
•Epi. & norepinephrine blood pressure
Regulation of energy availability:
•Insulin, glucagon and cortisol glucose
•Thyroid hormones basal metabolism
Hormone Synthesis & Release
Vescicular versus nonvescicular
The basal secretion is pulsatile (not continuous)
The secretory episodes may have different periodicity:•Circa-horal
•Circa-dian
•Circa-trigintan
•Circa-annual (seasonal)
Vescicular & Non-vesc. Secretion
Hormone Transport
Amine and Polypetide hormones usually circulate free in the bloodstream
•Exception: insulin-like growth factors
Steroids and thyroid hormones circulate bound to transport proteins:
•Specific: TBG for T4 and T3, SHBG for T and E2, CBG for cortisol
•Non-specific: albumin and pre-albumin
Hormone Transport
Binding influences clearance
Only the free hormone is “active”
Only the free hormone dictates the feedback
Mechanisms of Hormone Action
Cell surface receptors:
•Seven transmembrane receptors (G linked)
•Growth factor receptors
Nuclear receptors:
•Steroids receptor family
•Thyroid hormones receptor family
G-protein coupled Receptor
Nuclear Receptor
Effects of Hormone Action
Agonist
Weak agonist (partial agonist)
Antagonist
Hormone Metabolism & Clearance
Only a small fraction of circulating hormone is taken up by the target tissue
The bulk of clearance is done by liver and kidneys
Many kinds of enzymatic reactions: hydrolysis, oxidation, hydroxylation, methylation, decarboxylation, sulfation, glucuronidation
Only a small fraction is excreted intact in urine or feces
The feedbacks
controller
target
controller
target
a b a b
The negative feedback
Long loop: inhibition of pituitary secretion by hormones released by the target organs
Short loop: inhibition of hypothalamic secretion by pituitary hormones
Ultrashort loop: inhibition of hypothalamic secretion by hypothalamic hormones
Mechanisms of Endocrine Disease
Hypofuction (hormone deficiency)
Hyperfunction (hormone excess)
Hormone resistance:
•the hormone itself is abnormal
•the receptor is “blocked” by antibodies
•the receptor itself is abnormal
•the post-receptor pathway is abnormal