Enhanced 17 alpha-hydroxylation of pregnenolone and increased androgen production by rabbit adrenocortical cells stimulated chronically with corticotropin.
The postulated chronic stimulatory effect of corticotropin (ACTH) on pregnenolone production and on 17 alpha-hydroxylase activity was evaluated on adrenocortical cells obtained from control and chronically ACTH-treated rabbits. The cells were incubated with various concentrations of ACTH added alone or together with trilostane, so as to inhibit further conversion of pregnenolone and dehydroepiandrosterone. The maximal steroidogenic effect of ACTH (determined in the absence of trilostane) was increased 2-fold in adrenocortical cells from ACTH-treated animals; furthermore, cortisol production was increased whereas that of corticosterone decreased. While the generation of pregnenolone was of comparable magnitude for cells from both experimental groups, chronic in vivo treatment with ACTH was followed by a 40-fold enhancement in 17-hydroxypregnenolone production. Concomitantly, maximal DHEA production documented in the presence of ACTH and trilostane was enhanced more than 200-fold, from 0.45 +/- 0.20 pmol in control rabbits to 147 +/- 67 pmol in cells from ACTH-treated animals. The corresponding values of DHEA-sulphate production were 0.86 +/- 0.12 and 432 +/- 334 pmol, respectively. Thus, a prolonged stimulatory effect of ACTH on rabbit adrenocortical cells consists in an enhancement of the capacity to generate pregnenolone, and to convert this compound into 17-hydroxylated steroids.
D006907:17-alpha-Hydroxypregnenolone / Q000096:biosynthesis*; D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000096:biosynthesis; D019314:Dehydroepiandrosterone Sulfate; D006900:Hydroxylation; D066298:In Vitro Techniques; D008297:Male; D011284:Pregnenolone / Q000378:metabolism*; D011817:Rabbits; D013268:Stimulation, Chemical
D000728:Androgens; D006907:17-alpha-Hydroxypregnenolone; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D011284:Pregnenolone; D000324:Adrenocorticotropic Hormone