Effect of adrenocorticotrophin on cortisol and androstenedione secretion from dispersed cells of guinea-pig adrenal zonae fasciculata and reticularis.
We have studied cortisol and androstenedione secretion by dispersed cells of the outer zona fasciculata (ZF) plus zona glomerulosa, and the inner zona reticularis (ZR) plus medulla of the guinea-pig adrenal. The ZF and ZR were microdissected apart, the cells dispersed and incubated (200 000 cells/ml) for 90 min in the presence of adrenocorticotrophin (ACTH; 500 ng/l), dibutyryl cyclic AMP (dbcAMP; 1 mmol/l), pregnenolone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, 11-deoxycortisol and 21-deoxycortisol. The steroid concentrations were 5-25 mumol/l. Cortisol secretion was assayed by radioimmunoassay. There was no detectable cortisol secretion (less than 50 nmol/l) from the ZR in the controls (no additive) or after dbcAMP stimulation. Adrenocorticotrophin-stimulated cortisol secretion was also low (range less than 50-340 nmol/l). In contrast the ZF secreted 177-379 (control), 828-2052 (dbcAMP) and 2863-9735 (ACTH) nmol cortisol/l. There was no detectable (i.e. less than 2 nmol/l) cAMP production by ZR or ZF either basally (no ACTH) or after ACTH stimulation (500 ng/l). Challenge of the ZR cells with each cortisol precursor steroid (5 mumol/l) increased (P less than 0.05) cortisol secretion over that seen with the corresponding basal and ACTH-stimulated controls. Thus pregnenolone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, 11-deoxycortisol and 21-deoxycortisol (converted directly to cortisol by 21-hydroxylase) gave rise to (mean +/- S.D., n = 4) 406 +/- 86, 680 +/- 180, 1307 +/- 111, 1141 +/- 234 and 3160 +/- 419 nmol cortisol/l respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
D006907:17-alpha-Hydroxypregnenolone / Q000494:pharmacology; D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000735:Androstenedione / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D003350:Cortodoxone / Q000494:pharmacology; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000378:metabolism*; D006908:Hydroxyprogesterones / Q000494:pharmacology; D007536:Isomerism; D008297:Male; D009929:Organ Size; D011284:Pregnenolone / Q000494:pharmacology
D006908:Hydroxyprogesterones; C030228:11-hydroxyprogesterone; D006907:17-alpha-Hydroxypregnenolone; D000735:Androstenedione; D003994:Bucladesine; C003556:21-deoxycortisol; D011284:Pregnenolone; D000324:Adrenocorticotropic Hormone; D003350:Cortodoxone; D006854:Hydrocortisone