Chemical classification of hormones e Amino acid derivatives Dopamine, catecholamines and thyroid hormone ◆ Small neuropeptides Gonadotropin-releasing hormone(GnRh), thyrotropin- releasing hormone(tRh), somatostatin, and vasopressin Large proteins Insulin, luteinizing hormone(Lh), and parathyroid hormone (PTH) ◆ Steroid hormones Cortisol, estrogen ◆Ⅴ itamin derivatives Retinoids(vitamin a)and vitamin d
Chemical classification of hormones Amino acid derivatives • Dopamine, catecholamines, and thyroid hormone Small neuropeptides • Gonadotropin-releasing hormone(GnRH), thyrotropinreleasing hormone (TRH), somatostatin, and vasopressin Large proteins • Insulin, luteinizing hormone (LH), and parathyroid hormone (PTH) Steroid hormones • Cortisol, estrogen Vitamin derivatives • Retinoids (vitamin A) and vitamin D
Structure of hormones Protein and Peptide toroid Hormones Tyrosine Derivatives Hormones Prohormone Cholesterol osine OoUos0pODOOXO CH-COOH Endothelin NH Steroid Nucleus PoRNY yiren Epinephrine OH OH Insulin B Chain HN 000x CH OH A Chain ooooogmooopooooooodoo CH. NH CH, CH-COOH
Structure of hormones
Hormone synthesis and processing- peptide hormones Transcription factors ORNA A Polymerase DNA Promote Region ① Transcription 5 RNA Signal sequence 3 poly A Intron sequences Post-transcriptional Mature RNA 5'caD,EE:E AAAAA Pre-prohormone Translation HN ④ Post-translational Prohormone Golg Peptidases Hormone Secretory hormone fragment
Hormone synthesis and processing – peptide hormones
Hormone synthesis and processing - steroid hormones Cholesterol ◆ Synthesis of most adr/Adx steroid hormones CYP11A1 based on SULT2A1 FDHEA HSD3B2 →DHEA.f6 OH-DHEA modifications of the Androsterone. Etioch olanoione P9心[YP7A170HP9r YP17A Androstenedione precursor → Andro sterone CYP21A2 170HPregnanoloneHSD17BEtiocholanoione cholesterol CYP21A2 11-Deoxycorticosterone 11-Deoxycortisol Testosterone ◆ Multiple regulated ADR/Adx THDOC ADR/Adx s Androsterone CYP11B1CYP11B2 I CYP11B1H 21-Deoxycortisol Etiocholanolone enzymatic steps are Corticosterone Cortisol required for the CYP11B2 5aTHA, 5aTHBH6PDH addAx THA →TH.5cTHF synthesis of HSD11B1 HSD11B2 testosterone 180H-Corticosterone Cortisone ADR/A →180HTHA estradiol. cortisol CYP11B2 and vitamin d Aldosterone THALDO Mineralocorticoid
Hormone synthesis and processing – steroid hormones Synthesis of most steroid hormones is based on modifications of the precursor - cholesterol. Multiple regulated enzymatic steps are required for the synthesis of testosterone, estradiol, cortisol, and vitamin D
Transport of hormones in the circulation o Many hormones circulate in association with serum binding proteins Steroid and thyroid hormones are less soluble in aqueous solution than protein and peptide hormones and over 90% circulate in blood as complexes bound to specific plasma globulins or albumin o Bound and free hormones are in equilibrium T4 and T3 binding to thyroxine-binding globulin (tbg), albumin, and thyroxine-binding prealbumin(TBPa) Cortisol binding to cortisol-binding globulin( CBg
Transport of hormones in the circulation Many hormones circulate in association with serumbinding proteins. • Steroid and thyroid hormones are less soluble in aqueous solution than protein and peptide hormones and over 90% circulate in blood as complexes bound to specific plasma globulins or albumin. Bound and free hormones are in equilibrium. • T4 and T3 binding to thyroxine-binding globulin (TBG), albumin, and thyroxine-binding prealbumin (TBPA) • Cortisol binding to cortisol-binding globulin (CBG)