Mechanisms of interleukin-1-induced hormone secretion from the rat adrenal gland.

Abstract

The aim of these studies was to determine the intraadrenal mechanism of interleukin-1 (IL-1)-induced corticosterone release from the rat adrenal gland. To accomplish this, the role of catecholamines and eicosanoids on IL-1-induced corticosterone release was determined. Experiments were conducted on primary cultures of dispersed rat adrenal cells. Dose-dependent increases (P<0.05) in corticosterone concentration were observed when primary adrenal cells were incubated with different doses (10⁻¹⁰ to 10⁻⁸ M) of IL-1α. CL-1α and IL-1β elevated corticosterone release after a 24 hr incubation period. ACTH elevated corticosterone levels at 4 and 24 hr. The stimulatory effect of IL-1 on corticosterone release was mimicked by epinephrine (1 μM), and was selectively blocked by the α-adrenergic antagonist, phentolamine (10 μM). The β-adrenergic antagonist, propranolol (10 μM), did not change IL-1 induced corticosterone release. Neither phentolamine nor propranolol had an effect on ACTH stimulated corticosterone release. Both IL-1α and IL-1β significantly elevated (P<0.05) epinephrine levels after a 24 hr incubation period compared to media-treated controls. Untreated adrenal cells fixed for immunohistochemical staining with a specific anti-rat tyrosine hydroxylase antibody indicate that the primary adrenal cell preparation contained 3.1 ± 0.45% tyrosine hydroxylase positive cells. On the ultrastructural level, the chromaffin cells were found to be in direct cellular contact with cortical cells. Although IL-1α significantly increased (P<0.05) prostaglandin E₂ (PGE₂) levels from primary adrenal cells, the presence of the cyclooxygenase inhibitor, indomethacin (10 μM) significantly inhibited IL-1α-induced PGE₂ secretion without altering the effect of IL-1α on corticosterone release. Inhibitors of the lipoxygenase system (5-lipoxygenase, 10 μM) and the lipoxygenase and cytochrome P450 monooxygenase systems (nordihydroguaiaretic acid, 10 μM) did not effect IL-1α-induced corticosterone or PGE₂ release. These observations indicate that IL-1 stimulates the local release of catecholamines, which, in turn, stimulates corticosterone release through an α-adrenergic receptor; this mechanism is independent of PGE₂.