Introduction to Endocrine Pharmacology ผศ. พญ. มาลียา มโนรถ

Endocrine system Hormone-producing cells Circulating hormone Endocrine target cells

Hormones A substance that is release in one tissue and travels through the circulation (usually) to the target tissue.

Hormones Brain Pituitary hormone Thyroid gland : T3, T4 Gonadotropin-releasing hormone (GnRH) Pituitary hormone follicle-stimulating hormone (FSH) luetinizing hormone (LH) Thyroid gland : T3, T4

Hormones Adrenal gland : Pancrease : Ovary : GIT : Kidney : glucocorticoid, mineralocorticoid Pancrease : insulin Ovary : estrogen, progesterone GIT : gastrin Kidney : renin, erythropoietin

Types of Hormones Amino acid analogues & derivatives Polypeptides : thyroid hormones, catecholamines Polypeptides : insulin, parathyroid hormone Lipid : steroids, estrogen, progesterone

1. Hormone-producing cells Localized discrete gland dispersed throughout a larger organ Store the hormone in intracellular granules for release (insulin) Release to stimulation by increasing synthesis (steroid hormone)

Regulation of Hormonal Secretion By another hormone : corticotropin & cortisol By neural influences : Cholinergic stimulation of catecholamine release from the adrenal medulla Concentration of a circulating ion or metabolite : Ionized calcium & parathyroid hormone By all 3 kinds : Insulin-secreting beta cells of pancreatic islets

2. Circulating Hormone Chemical structure of a hormone Distribution Degradation Excretion Specific carrier protein Sex steroids (SHBG) Cortisol (CBG)

3. Endocrine target cells Specific hormone receptors Postreceptor events Gene-active hormones Membrane active hormones

Drug actions on hormone-producing cells 1. Act via hormone receptors Drug Action Clinical use OC ฏ GN Prevent ovulation Bromocriptine ฏ Prolactin Prolactinoma

Drug actions on hormone-producing cells 2. Do not act via hormone receptors Drug Action Clinical use SU ญ insulin DM Iodide ฏ T3, T4 Thyrotoxicosis Thionamides

Drug that act on endocrine target cells Binding to receptors Post receptor of hormone action 1. Gene-active hormones Steroid hormones Synthesis mRNA ญ Synthesis of proteins (lag period)

Drug that act on endocrine target cells Binding to receptors Post receptor of hormone action 2. Membrane-Active Hormones Peptide hormone (FSH, LH) Biogenic amines * Act by stimulating cAMP synthesis Adrenocorticotropic hormone (ACTH) Follicle-stimulating hormone (FSH) Luteinizing hormone (LH)

Other mechanism adenylate cyclase activity : PGE1 in adipose tissue Stimulate tyrosine-specific protein phosphorylation : insulin

cAMP dependent phosphorylation Rapid response (within seconds) only requires activation of enzymes already present in the cell Disappearance of the hormone is rapidly disappearance of its effect degradation of cAMP by phosphodiesterase dephosphorylation of kinase substrates by phosphatase

Hormone transport Polypeptide : Steroid & thyroid hormone : largely as free entities Steroid & thyroid hormone : largely bound to plasma protein 1-10% is free

Metabolism of hormones Polypeptide : Broken down to their component amino acid in the plasma Tissue proteases & peptidase Thyroid hormones : Metabolized largely by deiodination in peripheral tissues Steroid hormones : Metabolized conjugation (liver) urine