Elevated cortisol inhibits adrenocorticotropic hormone- and serotonin-stimulated cortisol secretion from the interrenal cells of the Gulf toadfish (Opsanus beta)

Abstract

Stimulation of the toadfish 5-HT1A receptor by serotonin (5-hydroxytryptamine; 5-HT) or 8-OH-DPAT, a 5-HT1A receptor agonist, results in a significant elevation in plasma cortisol. Conversely, chronic elevation of plasma cortisol has been shown to decrease brain 5-HT1A receptor mRNA and protein levels via the glucocorticoid receptor (GR); however, there appears to be a disconnect between brain levels of the receptor and cortisol release. We hypothesized that elevated plasma cortisol would inhibit both adrenocorticotropic hormone (ACTH)- and 5-HT-stimulated cortisol release from the interrenal cells of Gulf toadfish, that ACTH sensitivity would not be GR-mediated and 5-HT-stimulated cortisol release would not be via the 5-HT1A receptor. To test these hypotheses, interrenal cells from uncrowded, crowded, vehicle-, and cortisol-implanted toadfish were incubated with either ACTH, 5-HT or 5-HT receptor agonists, and cortisol secretion was measured. Incubation with ACTH or 5-HT resulted in a stimulation of cortisol secretion in uncrowded toadfish. Cortisol secretion in response to ACTH was not affected in crowded fish; however, interrenal cells from cortisol-implanted toadfish secreted significantly less cortisol than controls, a response that was not reversed upon treatment with the GR antagonist RU486. 5-HT-stimulated cortisol release was significantly lower from both crowded and cortisol-implanted toadfish interrenal cells compared to controls. Incubation with either a 5-HT4 or a 5-HT2 receptor agonist significantly stimulated cortisol secretion; however, incubation with 8-OH-DPAT did not, suggesting that the 5-HT1A receptor is not a mediator of cortisol release at the level of the interrenal cells. Combined, these results explain in part the disconnect between brain 5-HT1A levels and cortisol secretion.