EFFECTS OF ADRENOCORTICOTROPIN ON ADRENAL AND PLASMA - 11-BETA-HYDROXYANDROSTENEDIONE IN THE GUINEA-PIG AND DETERMINATION OF ITS RELATIVE ANDROGEN POTENCY

In order to gain a better understanding of adrenal steroid production in guinea pigs, adrenocorticotropin (ACTH) was administered to castrated adult guinea pigs and a series of C-21 and C-19 steroid levels were determined in both adrenals and plasma over a 6-h period. After injection of ACTH, adrenal cortisol and corticosterone concentrations were stimulated by almost 40- and threefold, respectively, whereas the content of C-21 steroid precursors, namely pregnenolone, 17-hydroxypregnenolone, progesterone, and 17-hydroxyprogesterone, was stimulated by two- to 10-fold. Increases of C-19 steroid levels, namely dehydroepiandrosterone (DHEA), androstenedione (4-DIONE), testosterone, and 11beta-hydroxyandrostenedione (11beta-DIONE) ranging from 1.5 to eight times were also observed in the adrenals. In castrated guinea pigs, basal plasma DHEA, 4-DIONE, and testosterone levels were undetectable by radioimmunoassay, whereas 11beta-DIONE concentrations were in a range similar to those in intact animals. In plasma, ACTH had a marked effect on corticosterone, cortisol, and 11beta-DIONE. The present results indicate that although guinea pig adrenals synthesized several C-19 steroids, only 11beta-DIONE was secreted by the adrenals into circulation even after administration of ACTH. The biological activity of this hydroxylated C-19 steroid was then assessed by using silastic implants in castrated guinea pigs, and it was shown that plasma 11beta-DIONE concentrations increased by threefold and had no effect on prostate weight. Moreover, by using ZR-75-1 cells, a mammary cancer cell line extremely sensitive to androgens, we demonstrated that 11beta-DIONE had an androgenic potency 35-fold less than that of dihydrotestosterone.