Androgen synthesis

Adrenal hormone production is controlled by the hypothalamus and pituitary gland. Corticotropin-releasing hormone (CRH) is secreted by the hypothalamus and stimulates secretion of adrenocorticotropic hormone (ACTH), also known as corticotropin from the anterior pituitary. ACTH, in turn, stimulates the adrenal cortex to produce cortisol. When sufficient or excessive cortisol levels are reached, a negative feedback is exerted on the secretion of CRH and ACTH, thereby decreasing overall cortisol production. The control of adrenal androgen synthesis also follows a similar negative-feedback mechanism. 

Androgen synthesis inhibitors provide symptomatic, but brief, relief in approximately 50% of patients. Aminoglutethimide causes adverse effects in 50% of patients, such as lethargy, ataxia, dizziness, and self-limiting rash. The adverse effects of ketoconazole are GI intolerance, transient increases in liver and renal function tests, and hypoadrenalism. 

A. 17,20 lyase is required for androgen synthesis, cyclooxygenase for prostaglandin production, 11- 3-hydroxysteroid dehydrogenase-2 acts as a reductase-converting cortisol to its inactive 11-keto derivative cortisone, whereas 18-hydroxylase is required for aldosterone production. 

Arlt W, Walker EA, Draper N, Ivison HE, Ride JP, Hammer F, Chalder SM, Borucka-Ankie-wicz M, Hauffa BP, Malunowicz EM, Stewart PM, Shackleton CH (2004) Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and human androgen synthesis analytical study. Lancet 363 2128-2135... 

Androgen synthesis in the human male fetus begins at the age of about 70 days when the testes enlarge and go through an important period of activity that begins the conversion of the infant body to a male type. Other bursts of testosterone synthesis occur during infancy, but there is little further synthesis until the onset of puberty.268 272... 

General anabolic effects stimulates release of insulinlike growth factor-I Stimulates milk synthesis Ovary luteinization, progesterone synthesis testis interstitial cell development, androgen synthesis... 

Miller WL. Disorders of androgen synthesis—from cholesterol to dehydroepiandrosterone. Med Princ Pract. 2005 14(suppl l) 58-68. 

Pharmacokinetics Itraconazole is well-absorbed orally and food increases its bioavailability. It is extensively bound to plasma proteins and distributes well throughout most tissues, including bone, sputum and adipose tissues. However, therapeutic concentrations are not attained in the CSF. Like ketoconazole it is extensively metabolized in the liver but does not inhibit androgen synthesis. Little of the parent drug appears in the urine and thus doses do not have to be reduced in renal failure. 

Cyproterone acetate Androgen synthesis inhibition Aminoglutethimide Ketocon azole Progesterones ... 

---