1. Introduction to Endocrine Pharmacology
ผศ. พญ. มาลียา มโนรถ

2. Endocrine system Hormone-producing cells Circulating hormone
Endocrine target cells

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

4. 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

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

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

8. 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)

9. 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

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

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

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

13. 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

14. 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)

15. 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)

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

17. 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

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

19. 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