Endocrine interactions: adrenal steroids and precursors.

Adult male rats (n = 48) were castrated and treated daily for 4 wk with adrenal steroids in the presence or absence of adjuvant testosterone. Dehydroepiandrosterone (DHEA), DHEA sulfate, and androstenedione (2 mg/kg body wt) were administered as cyclodextrin complexes to mimic the pharmacodynamics of the endogenous products. Although they are the substrates for testosterone synthesis in target tissues, supplements of adrenal steroids alone were unable to maintain integrity of sociosexual responses and androgen target tissues after castration. More surprising, groups administered adrenal precursor plus testosterone showed substantial suppression of the typical restoration of reproductive systems in castrates receiving androgen therapy. The adrenal steroids, however, were not functionally identical. Each steroid interacted with testosterone to leave its own distinctive "footprint" on androgen-sensitive systems. The conclusion is that the endogenous adrenal products are not simply passive precursors of testosterone. Adrenal steroids may serve as endocrine regulators of androgen bioavailability and bioactivity.