Androgens biologic function

The human adrenal cortex secretes three major classes of steroid hormones that possess a wide range of physiological functions. These include the glucocorticoids, the mineralo-corticoids, and the adrenal androgens. This chapter begins with a section on general steroid biochemistry, followed by a discussion of the clinical and biological functions of the steroid hormones produced by the adrenal cortex. 

Adrenocortical steroid hormones have a vast array of biological functions. Cortisol, the primary human glucocorticoid, regulates the inflammatory response (Newton and Holden, 2007), carbohydrate and lipid metabolism, and stress response (Kassel and Herrlich, 2007). Aldosterone regulates blood pressure by modulating fluid and electrolyte balance (Brizuela et ah, 2006 Foster, 2004). In the adrenal cortex, dehydroepiandrosterone (DHEA), dehy-droepiandrosterone sulfate (DHEA-S), and androstenedione are the androgens produced (Havelock et ah, 2004 Rainey et ah, 2002). 

He, B., Kemppainen, J.A., Voegel, J.J., Gronemeyer, H. and Wilson, E.M. (1999) Activation function 2 in the human androgen receptor ligand binding domain mediates interdomain communication with the NH2-terminal domain. The Journal of Biological Chemistry, 274, 37219-37225. 

Dehm, S.M. and Tindall, D.J. (2006) Ligand-independent androgen receptor activity is activation function-2-independent and resistant to antiandrogens in androgen refractory prostate cancer cells. The Journal of Biological Chemistry, 281, 27882-27893. 

The biological significance of these secondary products in normal states is as yet unknown. In particular, the possible hormonal function of DHA-sulfate is an intriguing mystery in view of its large plasma concentration and secretion rates and its negligible androgenic activity. Its role as a provocative factor in acute porphyria has recently been suggested, and it has been shown to increase the activity of hepatic amino-levulinate synthetase (G6). 

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