Stimulation of steroidogenesis by forskolin in rat adrenal zona glomerulosa cell preparations.
The actions of forskolin have been investigated to determine to what extent its effects on steroidogenesis in rat adrenal preparations are dependent on activation of adenylate cyclase. In zona glomerulosa preparations, stimulation of both aldosterone and corticosterone production was obtained at concentrations of forskolin between 1 and 10 mumol/l. The effects of 10 mumol forskolin/l were additive with those of low doses (1 pmol/l) of corticotrophin (ACTH), but not with those of high doses (1 nmol/l) of ACTH. In contrast, in zona fasciculata/reticularis cells, doses of forskolin up to 10 mumol/l produced no significant stimulation of corticosterone production either alone or in the presence of ACTH (1 pmol/l and 1 nmol/l). The response to 1 nmol ACTH/l was attenuated in the presence of forskolin (10 mumol/l) in both zona glomerulosa and zona fasciculata/reticularis cell preparations. Cyclic AMP production increased progressively with dose up to 100 mumol forskolin/l in zona glomerulosa cells, whereas corticosterone production was maximal between 10 and 30 mumol forskolin/l and decreased at 100 mumol forskolin/l. In zona fasciculata/reticularis cells, cyclic AMP production was also increased by forskolin (1 and 10 mumol/l). The stimulation of zona glomerulosa steroidogenesis by forskolin (1-10 mumol/l) and ACTH (1-100 pmol/l) were both reduced by the adenylate cyclase inhibitor, N6-phenylisopropyladenosine (100 mumol/l). The calcium channel inhibitor, nifedipine, only reduced the steroidogenic response to forskolin (3 mumol/l) at doses of 300 mumol/l whereas the response to 8.4 mmol K+/l was inhibited at 10 mumol nifedipine/l.(ABSTRACT TRUNCATED AT 250 WORDS)
Purdy
S J
SJ
Biomedical Sciences Division, King's College London.
Whitehouse
B J
BJ
Abayasekara
D R
DR
D000262:Adenylyl Cyclases / Q000378:metabolism; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000096:biosynthesis; D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology*; D003345:Corticosterone / Q000096:biosynthesis; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D051381:Rats; D013268:Stimulation, Chemical; D015384:Zona Glomerulosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D005576:Colforsin; D010660:Phenylisopropyladenosine; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D009543:Nifedipine; D003345:Corticosterone