Reproductive Module Lecture 1 Dr Halima Babiker Overview

Reproductive Module Lecture 1 Dr. Halima Babiker

Overview of Steroid Hormones Ø Steroid hormones: produced in the adrenal cortex, testis, ovary, and some peripheral tissues (adipose tissue, the brain!) Ø All steroid hormones are derived from cholesterol and differ only in the ring structure and side chains attached to it.

Steroid hormones § The core of steroids is composed of seventeen carbon atoms bonded together that take the form of four fused rings. § Three cyclohexane rings (designated as rings A, B, and C ) and one cyclopentane ring (the D ring). § The steroids vary by the functional groups attached to this four ring core and by the oxidation state of the rings.

C A B D

steroids based upon their chemical composition Examples Number of carbon atoms cholesterol 27 cholic acid 24 progesterone 21 testosterone 19 estradiol 18

Types of steroid hormones Glucocorticoids; cortisol is the major representative in most mammals Mineralocorticoids; aldosterone being most prominent Androgens such as testosterone Estrogens, including estradiol and estrone Progestogens (also known a progestins) such as progesterone

Steroid hormones § Are not packaged, but synthesized and immediately released § Enzymes which produce steroid hormones from cholesterol are located in mitochondria and smooth ER § Steroid hormones are not water soluble so have to be carried in the blood complexed to specific binding globulins. § Corticosteroid binding globulin carries cortisol § Sex steroid binding globulin carries testosterone and estradiol

Functions of Steroid Hormones Ø Steroid hormones play important roles in: - carbohydrate regulation (glucocorticoids) - mineral balance (mineralocorticoids) - reproductive functions (gonadal steroids) Ø Steroids also play roles in inflammatory responses, stress responses, bone metabolism

Steroid hormone synthesis Ø A series of enzymatic steps in the mitochondria and ER of steroidogenic tissues convert cholesterol into all of the other steroid hormones and intermediates. Ø The rate-limiting step in this process is the transport of free cholesterol from the cytoplasm into mitochondria Ø This step is carried out by the Steroidogenic Acute Regulatory Protein (St. AR)

Cholesterol is precursor for 5 steroid hormone classes • Progestagens (e. g. Progesterone) • Glucocorticoids (e. g. Cortisol) • Mineralcorticoids (e. g. Aldosterone) • Androgens (e. g. Testosterone) • Estrogens Synthesis sites • Adrenal cortex: Glucocorticoids, Mineralcorticoids • Women • Corpus luteum: Progestagens • Ovary: Estrogens • Men • Testis: Testosterone

Enzymes involved in steroid biosynthesis § Desmolases (or lyases): these enzymes catalyse reactions which result in the removal of parts of the original cholesterol side-chain. This involves hydroxylation and requires a cytochrome P-450, molecular oxygen (O 2) and (NADPH) as a cofactor. § These enzymes are located in the mitochondria. § Hydroxylases: these enzymes are membrane-bound are present either in the mitochondrial or in the microsomal fraction of the cell. They also require a cytochrome P-450, molecular oxygen and NADPH, as for lyases. § § Hydroxysteroid dehydrogenases (oxido-reductases): these enzymes catalyse reversible reactions. They are found both in the cell cytosol and in the microsomal fraction. § Aromatase: conversion of the A-ring to a phenolic structure (i. e. with a phenolic HO-group at C-3), a process known as " aromatization ",

21 -hydroxylase

Steroid Hormone Synthesis

Functions of Hormones Derived from Cholesterol Product Functions Progesterone prepares uterus lining for implantation of ovum Glucocorticoids (cortisol) promote gluconeogenesis; anti-inflammatory Mineralocorticoids (aldosterone) maintains blood volume and blood pressure by increasing sodium reabsorption by kidney

Functions of Hormones Derived from Cholesterol Product Functions Androgens (strongest = testosterone) development of male secondary sex characteristics Estrogen development of female secondary sex characteristics; prevents bone resorption Vitamin D (not a steroid hormone) intestinal calcium absorption; promotes bone formation; prevents phosphate loss by kidneys

Catabolism of stroids § Steroids are oxidized mainly by cytochrome P 450 oxidase enzymes. § These reactions introduce oxygen into the steroid ring and allows the structure to be broken up by other enzymes, to form bile acids as final products. § These bile acids can then be eliminated through secretion from the liver in the bile.

Over use of anabolic steroids

Home work No 1 (Assignment ) Write About Major pathway for steroid hormones biosynthesis