Enhanced androgen production by rabbit adrenocortical cells stimulated chronically with corticotropin: evidence for increased 17 alpha-hydroxylase activity.
The effects of prolonged treatment with corticotropin (ACTH1-24, 200 micrograms s.c. daily during 12 days) on the production of androgens and glucocorticoids were studied on rabbit dispersed adrenocortical cells. The steroidogenic capacity of adrenocortical cells, expressed in terms of the maximal response to ACTH of glucocorticoid (i.e. corticosterone and cortisol) production, was significantly increased after treatment with ACTH. This was associated with a loss of sensitivity to this peptide: indeed, the concentration of ACTH required to induce a half maximal secretory response was one order of magnitude higher with cells from ACTH-treated animals. Among the C21 steroids measured the changes observed involved the 17 alpha-hydroxylated compounds (cortisol, cortisone, 11-deoxycortisol) while corticosterone production was significantly depressed. This effect of prolonged ACTH treatment on steroidogenic pathways involving 17 alpha-hydroxylation, was further evidenced by a clear-cut enhancement in androgen secretion (dehydroepiandrosterone, androstenedione and testosterone) by adrenocortical cells from ACTH-treated animals. The changes observed after treatment of the animal with ACTH were equally obvious, whether the adrenocortical cells were incubated with ACTH or with dibutyryl-c-AMP.
D000302:Adrenal Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000728:Androgens / Q000096:biosynthesis*; D000735:Androstenedione / Q000096:biosynthesis; D000818:Animals; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000096:biosynthesis; D019314:Dehydroepiandrosterone Sulfate; D004789:Enzyme Activation / Q000187:drug effects; D005938:Glucocorticoids / Q000096:biosynthesis; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011817:Rabbits; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000378:metabolism*; D013739:Testosterone / Q000096:biosynthesis
D000728:Androgens; D005938:Glucocorticoids; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D000324:Adrenocorticotropic Hormone; D013250:Steroid Hydroxylases; D013254:Steroid 17-alpha-Hydroxylase