Adult male rats (n = 48) were castrated and treated daily for 4 wk wit
h 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 th
e pharmacodynamics of the endogenous products. Although they are the s
ubstrates for testosterone synthesis in target tissues, supplements of
adrenal steroids alone were unable to maintain integrity of sociosexu
al responses and androgen target tissues after castration. More surpri
sing, groups administered adrenal precursor plus testosterone showed s
ubstantial suppression of the typical restoration of reproductive syst
ems in castrates receiving androgen therapy. The adrenal steroids, how
ever, were not functionally identical. Each steroid interacted with te
stosterone to leave its own distinctive ''footprint'' on androgen-sens
itive systems. The conclusion is that the endogenous adrenal products
are not simply passive precursors of testosterone. Adrenal steroids ma
y serve as endocrine regulators of androgen bioavailability and bioact
ivity.