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