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 11 beta-hydroxyandrostenedione (11 beta-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 11 beta-DIONE concentrations were in a range similar to those in intact animals. In plasma, ACTH had a marked effect on corticosterone, cortisol, and 11 beta-DIONE. The present results indicate that although guinea pig adrenals synthesized several C-19 steroids, only 11 beta-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 11 beta-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 11 beta-DIONE had an androgenic potency 35-fold less than that of dihydrotestosterone.
CHUL Research Center, Sainte-Foy, Quebec, Canada.
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D000305:Adrenal Cortex Hormones / Q000097:blood / Q000378:metabolism; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003345:Corticosterone / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000033:anatomy & histology; D014407:Tumor Cells, Cultured
D000305:Adrenal Cortex Hormones; D000735:Androstenedione; C003582:11-hydroxyandrostenedione; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone; D006854:Hydrocortisone