Calcium, a "third messenger" of cAMP-stimulated adrenal steroid secretion.
This study examines the role of extracellular calcium and calcium mobilization from intracellular stores in mediating cAMP-stimulated steroid secretion by rat adrenal glomerulosa cells (GC) and fasciculata cells (FC). When GC were incubated acutely in a calcium-deficient buffer, cAMP failed to significantly increase aldosterone secretion above base line. Aldosterone secretion, however, rose from 17 +/- 2 to 32 +/- 4 ng/10(6) cells (P less than 0.01) as calcium in the medium was increased from 0 to 3.5 mM. In contrast, cAMP-stimulated corticosterone production by FC was not influenced by changes in the external calcium concentration. Lanthanum (10(-4) M), an inhibitor of calcium influx, reduced cAMP-stimulated aldosterone secretion from 69 +/- 10 to 42 +/- 5 ng/10(6) cells (P less than 0.01) but failed to alter cAMP-stimulated fasciculata steroidogenesis. Depletion of intracellular calcium stores, achieved by incubating with EGTA, markedly blunted cAMP-stimulated corticosterone secretion in GC from 666 +/- 126 to 32 +/- 6 ng/10(6) cells (P less than 0.01), and cAMP-stimulated corticosterone secretion in FC from 2,223 +/- 407 to 414 +/- 58 ng/10(6) cells (P less than 0.01). TMB-8, a putative inhibitor of intracellular calcium mobilization, markedly inhibited (P less than 0.01) cAMP-stimulated aldosterone secretion by GC from 469 +/- 31 to 48 +/- 8 ng/10(6) cells and corticosterone secretion by FC from 9,867 +/- 1,821 to 2,832 +/- 586 ng/10(6) cells. These observations suggest that cAMP activation of adrenal steroidogenesis requires the release of calcium from intracellular stores.(ABSTRACT TRUNCATED AT 250 WORDS)
Schiebinger
R J
RJ
Braley
L M
LM
Menachery
A
A
Williams
G H
GH
D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000305:Adrenal Cortex Hormones / Q000378:metabolism*; D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology*; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D051381:Rats; D011919:Rats, Inbred Strains
D000305:Adrenal Cortex Hormones; D002121:Calcium Channel Blockers; D000450:Aldosterone; D004533:Egtazic Acid; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D000242:Cyclic AMP; D002786:Cholesterol Side-Chain Cleavage Enzyme; D002118:Calcium; D003345:Corticosterone