Sex Steroids Biosynthesis in Medicine

Steroid Hormones Biosynthesis Overview

• Cholesterol is the precursor of all classes of steroid hormones: glucocorticoids, mineralocorticoids, and sex hormones (androgens, estrogens, and progestins).
• Synthesis and secretion occur in the adrenal cortex (cortisol, aldosterone, and androgens), ovaries and placenta (estrogens and progestins), and testes (testosterone).
• Steroid hormones are transported by the blood from their sites of synthesis to their target organs, complexed with a plasma protein.

Regulation of Steroid Hormone Synthesis

• The testes and ovaries (gonads) synthesize hormones necessary for sexual differentiation and reproduction.
• A single hypothalamic-releasing factor, gonadotropin-releasing hormone, stimulates the anterior pituitary to release the glycoproteins luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
• LH stimulates the testes to produce testosterone and the ovaries to produce estrogens and progesterone.
• FSH regulates the growth of ovarian follicles and stimulates testicular spermatogenesis.

Mechanism of Action of Steroid Hormones

• Each steroid hormone diffuses across the plasma membrane of its target cell and binds to a specific cytosolic or nuclear receptor.
• The receptor-ligand complexes accumulate in the nucleus, dimerize, and bind to specific regulatory DNA sequences (hormone response elements [HRE]) in association with coactivator proteins, thereby causing increased transcription of targeted genes.

Synthesis of Androgens (Male Sex Hormones)

• They contain 19 carbon atoms and are secreted by the Leydig cells of the testis.
• The main hormone secreted by the testis is testosterone, which acts as a prohormone and is converted in target tissues to the more active form dihydrotestosterone (DHT).
• Small amounts of testosterone are formed in females by the ovaries and adrenal cortex.

Metabolic Role of Androgens

• Both testosterone and DHT are anabolic and growth-promoting hormones.
• They stimulate the development and maintenance of normal structure and function of the male sex organs, and influence the development of male sex characters.
• They stimulate spermatogenesis, and have effects on protein metabolism, carbohydrate metabolism, and skeletal growth.

Defects in Androgens Synthesis

• A defect in the activity or amount of an enzyme in the pathway of steroid hormones synthesis can lead to a deficiency in the synthesis of hormones beyond the affected step and to an excess in the hormones or metabolites before that step.
• These disorders are known as the congenital adrenal hyperplasias (CAH), resulting in enlarged adrenals.

Inactivation of Androgens

• They are inactivated in the liver and excreted in the urine in conjugation with glucuronic acid or sulphuric acid.
• Excretory metabolites include androsterone and etiocholanolone.

Synthesis of Estrogens (Female Sex Hormones)

• Estrogens are produced by cells of developing Graffian follicles.
• They contain 18 carbon atoms and are characterized by having a phenolic ring A.
• They include estrone (E1), estradiol (E2), which is the most potent, and estriol (E3).
• Estradiol is secreted mainly by the ovaries in females and also formed by the placenta during pregnancy.
• Small amounts of estrogens are secreted by the testis and adrenal cortex in males.

Metabolic Role of Estrogens (Female Sex Hormones)

• They have effects on the female genital system, including the development of female sex organs and female sexual characters.
• They stimulate the development and growth of the female mammary duct system, and proliferation of vaginal epithelium and endometrium.
• They have effects on protein metabolism, lipid metabolism, and bone metabolism.

Inactivation of Estrogens (Female Sex Hormones)

• Estradiol is converted to the less active estrone and estriol in the liver, which are excreted in the urine in conjugation with glucuronic acid or sulphuric acid.

Synthesis of Progesterone (Female Sex Hormone)

• It contains 21 carbon atoms.
• It is produced by the ovaries and placenta, and has effects on the female genital system and reproductive cycle.

Explore the biosynthesis of sex steroids, including enzymes involved, regulation, disorders, and metabolic effects. Ideal for medicine and surgery students.