Effects of Proopiomelanocortin Peptides and Angiotensin II on Steroidogenesis in Isolated Aldosteronoma Cells

Abstract

Cells isolated from five aldosterone-producing adenomas were used to study glucocorticoid and aldosterone production in response to ACTH, angiotensin II (A IÍ), and peptides derived from proopiomelanocortin (POMC), viz. the 16K N-terminal fragment (16K) and its derivative, γ₃MSH and the C-terminal fragment β-lipotropin (βLPH) and its derivative β-endorphin. At concentrations similar to those of ACTH and A II (10⁻¹²–10⁻¹⁰ M), 16K, γ₃MSH, and 0LPH selectively stimulated aldosterone production, which reached levels close to those obtained with AII. ACTH, however, was the most effective stimulant of steroidogenesis. The 16K, γ₃MSH, and βLPH peptides potentiated the action of ACTH, particularly in the case of aldosterone production. β-Endorphin, whether used alone or in association with ACTH, had no effect on steroidogenesis at the dose used (10⁻10 M).

The principal glucocorticoid products of the adenoma cells were cortisol and corticosterone. The ratios of corticosterone to cortisol (B/F) and aldosterone to corticosterone (A/B) varied considerably from one adenoma to another, both basally and in response to ACTH. Nevertheless, within individual adenomas, the mean B/F ratio induced by ACTH [0.280 ± 0.013 (±SEM)] was significantly larger than that induced by A II (0.127 ± 0.007; P < 0.001). By contrast, the A/B ratio in response to ACTH (0.061 ± 0.003) was significantly smaller than that in response to A II (0.159 ± 0.010; P < 0.001). The values obtained with 16K (B/F, 0.106 ± 0.010; A/B, 0.192 ± 0.028) and γ₃MSH (B/F, 0.122 ± 0.012; A/B, 0.178 ± 0.020) were close to those obtained with A II. 16K and γ₃MSH potentiated ACTH's effect on steroidogenesis mainly by increasing the A/B ratio from 0.061 ± 0.003 for ACTH alone to 0.100 ± 0.008 for 16K plus ACTH (P < 0.005) and to 0.092 ± 0.005 for γ₃MSH plus ACTH (P < 0.001).

The findings suggest that the stimulation of aldosterone production by 16K and γ₃MSH in aldosteronoma cells is of the A II type and that these peptides may play a role in the genesis of primary aldosteronism.