Download PowerPoint

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
Some Definitions II
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)
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
Posterior Hypophysis
Thyroid
Parathyroid
Adrenal Cortex
Adrenal Medulla
Testis
Ovary
Pancreatic Islets
Placenta
ACTH, TSH, LH, FSH, GH, PRL
Oxytocin and ADH
T4, T3 and calcitonin
PTH
Aldosteron, Cortisol, DHEA et al.
Epinephrine and Norepinephrine
Testosterone, Inhibin
Estradiol, androgens
Insulin, glucagon, somatostatin, etc
hCG, hPL, estradiol, progesterone
“Non-classic” Endocrine
Glands
Brain
CRH, TRH, GnRH, dopamine,
GHRH, somatostatin
Heart
Kidney
Liver
Stomach
Small intestine
Atrial natriuretic peptide
Renin, 1,25-Vit. D, erythropoietin
Insulin-like growth factor-1
Gastrin
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)
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
•Aldosterone
•PTH, Vit. D, calcitonin
•Epi. & norepinephrine
water
Na and K
calcium and phosphate
blood pressure
Regulation of energy availability:
•Insulin, glucagon and cortisol
•Thyroid hormones
glucose
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
controller
a
b
target
a
b
target
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
•
•
•
•