1. Reproductive Module Dr.Halima Babiker

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

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

4. C B A D

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

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

7. 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

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

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

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

11. 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 (O2) and (NADPH) as a cofactor.  These enzymes are located in the mitochondria.  Hydroxylases : these enzymes are membrane-bound and 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 ",

13. 21-hydroxylase

14. Steroid Hormone Synthesis

15. Functions of Hormones Derived from Cholesterol ProductFunctions 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

16. Androgens (strongest = testosterone) (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 ProductFunctions Functions of Hormones Derived from Cholesterol

17. Catabolism of stroids  Steroids are oxidized mainly by cytochrome P450 oxidase enzymes. cytochrome P450 oxidasecytochrome P450 oxidase  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. bile acidsbile acids  These bile acids can then be eliminated through secretion from the liver in the bile. liverbileliverbile

18. Over use of anabolic steroids

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