Hormone structure and biosynthesis of steroid hormones

Four major chemical classes of hormones

Steroid hormones- Testosterone, cortisol, progesterone, estrogen

peptide/protein hormones- Growth hormone, insulin, glucagon

amino acid derivatives-Epinenophrine, thyroid hormone, dopamine

eicosanoids (Fatty acid derivatives)-Prostaglandins and relative compounds

3 functional modes of hormone action

Endocrine (Transport in the bloodstream to target distant cells)

paracrine (local diffusion to neighbourhood cells)

autocrine (

Intracrine (within the same cell

Parental precursor for all steroid hormones

Cholesterol (C27)

Core ring structure of steroid molecules

cyclopentanoperhydrophenanthrene (Sterane ring)

Rate-limiting enzyme in de novo cholesterol synthesis

HMG—CoA reductase (converts 3-hydroxy-3-methylglutaryl-CoA to mevalonate)

Rate-limiting step in steroidogenesis

Transport of free cholesterol from the cytoplasm across the outer to the inner mitochondrial membrane by StAR protein

Steroidogenic acute regulatory protein (StAR)

A 30kDa short-lived mitochondrial protein that facilitates cholesterol transport into the inner mitochondrial membrane

Enzyme converting cholesterol to pregenelone

CYP11A1 (cholesterol side-chain cleavage enzyme/P450scc)

Enzyme deficiency in lipoid congenital adrenal hyperplasia (LCAH)

Mutation or deficiency in the stAR protein

Primary mineralocorticoid and site of synthesis

Aldosterone, synthesized in the zona glomerulosa of the adrenal cortex

Primary glucocorticoid in humans and site of synthesis

Cortisol, synthesized in the zona fasciculata of the adrenal cortex

Enzyme responsible for converting testosterone.androgens into estrogens

aromatase (CYP19)

Enzyme converting progesterone to 11-deoxycorticosterone and 17\alpha-OH-progesterone to 11-deoxycortisol

21-hydroxylase (CYP21A2)

Enzyme catalyzing 11-deoxycortisol to cortisol conversion

11\beta-hydroxylase (CYP11B1)

Enzyme unique to the zona glomerulosa for alderserone synthesis

aldersterone synthesis (CYP11B2)

Enzyme converting testosterone to dihydrotestosterone (DHT)

5\alpha-reductase

Role of 3B-hydroxysteroid dehydrogenase (3B-HSD)

Converts

Sterochemical notation B-positiuon on a steroid ring

Substituent points upward (above the plane of the ring, solid wedge)

Biochemical definition of cushings syndrome

Hyperfunction of the adrenal cortex resulting from excess cortisol production or exogenous corticosteroid use

Biochemicaal definition of addisons disease

Primary adrenal insufficiency (hypofunction) causing deficient cortisol and aldosterone production

Functional role of 17a-hydroxylase/17/20-lyase (CYP17A1)

Hydroxylates C17 and cleaves the side-chain to yield C19 adrenal-gonadal androgen precursors

Carbon count differences: cholesterol vs glucocorticoids vs estrogens

Cholesterol (C27)

Progestogens/glucocorticocoids/mineralcorticoids (C21), androgens (C19), estrogens (C18)

Transport method of steroid hormones in circulation

Bound to plasma carrier proteins (corticosteroid-binding globulin, sex hormone-binding globulin, aldubmin) only free steroids are biologically active

Subcvelluklar localization of steridogenic enzymes

Partitioned between the inner mitochrondrial membrane (CYP11A1, CYP11B1, CYP11B2) and smooth endoplasmic reticulum (CYP17, CYP21, 3B-HSD, CYP19)

Replacement protein for StAR in the placenta

MLN64 protein