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)