Mechanisms of interleukin-1-induced hormone secretion from the rat adrenal gland.
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-1 alpha. IL-1 alpha and IL-1 beta 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 microM), and was selectively blocked by the alpha-adrenergic antagonist, phentolamine (10 microM). The beta-adrenergic antagonist, propranolol (10 microM), did not change IL-1 induced corticosterone release. Neither phentolamine nor propranolol had an effect on ACTH stimulated corticosterone release. Both IL-1 alpha and IL-1 beta 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-1 alpha significantly increased (P < 0.05) prostaglandin E2 (PGE2) levels from primary adrenal cells, the presence of the cyclooxygenase inhibitor, indomethacin (10 microM) significantly inhibited IL-1 alpha-induced PGE2 secretion without altering the effect of IL-1 alpha on corticosterone release. Inhibitors of the lipoxygenase system (5-lipoxygenase, 10 microM) and the lipoxygenase and cytochrome P450 monooxygenase systems (nordihydroguaiaretic acid, 10 microM) did not effect IL-1 alpha-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 alpha-adrenergic receptor; this mechanism is independent of PGE2.
Gwosdow
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AR
Endocrine Unit/Bulfinch 3, Massachusetts General Hospital, Boston, USA.
D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002395:Catecholamines / Q000502:physiology*; D002478:Cells, Cultured; D003345:Corticosterone / Q000378:metabolism*; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D015232:Dinoprostone / Q000502:physiology; D015777:Eicosanoids / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology*; D008084:Lipoxygenase / Q000502:physiology; D010105:Oxygenases / Q000502:physiology; D051381:Rats; D013268:Stimulation, Chemical
D002395:Catecholamines; D015777:Eicosanoids; D007375:Interleukin-1; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D008084:Lipoxygenase; D000090762:Cytochrome P-450 CYP2J2; D015232:Dinoprostone; D003345:Corticosterone