Testosterone synthesis, suppression

Mechanism of Action A testosterone derivative that suppresses the pituitary-ovarian axis by inhibiting the output of pituitary gonadotropins. Causes atrophy of both normal and ectopic endometrial tissue in endometriosis. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are depressed in fibrocystic breast disease. Inhibits steroid synthesis and binding of steroids to their receptors in breast tissues. Increases serum levels of esterase inhibitor. Therapeutic Effect Produces anovulation and amenorrhea, reduces the production of est rogen, corrects biochemical deficiency as seen in hereditary angioedema. 

Severe consequences can occur from defective syn- thesis of a steroid hormone, as is the case in several metabolic diseases. Patients who have 21-hydroxylase deficiency are unable to convert progesterone to aldosterone and cortisol. Instead the progesterone is directed to an excess production of testosterone. In the female, this results in masculinization and hirsutism (growth of hair). In the male, premature masculinization occurs. If the disease is diagnosed before the first birthday, the patient can be treated with the missing steroid hormones, which in turn suppress the synthesis of excess progesterone and, as a consequence, testosterone via feedback mechanisms. 

The third way testosterone affects fat synthesis is not positive. When testosterone levels are elevated, more is converted into estrogens by way of the conversion enzyme aromatase. This is called aromatization, an important word to understand before reading the rest of this book Estrogen in turn increases female pattern fat deposits and suppresses HPTA function. Atleast estrogen can increase GH production. 

Ketoconazole [kee toe KON a zole], a substituted imidazole, is one of a family of azoles useful in treating systemic mycoses. In addition to its antifungal activity, ketoconazole also inhibits gonadal and adrenal steroid synthesis in humans by blocking C17-20 lyase, Up-hydroxylase, and cholesterol side-chain cleavage thus, it suppresses testosterone and cortisol synthesis. 

Cadmium decreases testosterone production by preventing the synthesis of cholesterol, a precursor of all steroid hormones. Other chemicals that interfere with steroid hormone synthesis include aminoglute-thimide, cyanoketone, and ketoconazole. Copper chelating compounds, such as dithiocarbamates, metam sodium, and carbon disulfide, suppress the conversion of dopamine to norepinephrine and subsequently to epinephrine. 

During development, a portion of the mesonephric kidney develops into two different ducts, the Wolffian and Mullerian ducts. The Wolffian duct, under the influence of testosterone, differentiates into the vas deferens, the epididymis, and the seminal vesicle. A second pair of embryonic ducts, the Mullerian ducts, develops alongside the Wolffian ducts. In males, the Mullerian ducts are suppressed due to the action of Miillerian-inhibiting substance (MIS), a hormone secreted by the testes. Maleness depends upon the secretion of testosterone from the testis, and in the absence of testosterone a male will develop a female phenotype. The SRY gene apparently activates the synthesis of MIS, which in turn assures that the Mullerian ducts will atrophy and that the mammal develops as a male. 

Ketoconazole also suffers from a number of other clinical disadvantages. At daily doses greater than 400 mg ketoconazole may reversibly inhibit endogenous steroid synthesis with resultant suppression of testosterone and... 

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