Glucocorticoid Secretion In Rats Research Articles

Extended light exposure suppresses nocturnal increases in cytotoxic activity of splenic natural killer cells in rats

To understand light-induced immune modulation in vivo, we evaluated the effect of nocturnal light exposure on splenic natural killer (NK) cell activity in rats. Nocturnal increases in the number and cytotoxic activity of NK cells were significantly suppressed under extended light exposure. Nocturnal increases in serum corticosterone levels were also suppressed by light exposure, suggesting that the light exposure-induced decrease in NK cell functions was not due to stress-induced glucocorticoid secretion in rats. These results suggest that nocturnal light exposure could profoundly affect NK cell functions perhaps through eye–brain hormonal modulation.

Gastric inhibitory polypeptide stimulates glucocorticoid secretion in rats, acting through specific receptors coupled with the adenylate cyclase-dependent signaling pathway

Gastric inhibitory polypeptide (GIP) is a 42-amino acid peptide, belonging to the VIP-secretin-glucagon superfamily, some members of this group are able to regulate adrenocortical function. GIP-receptor mRNA has been detected in the rat adrenal cortex, but investigations on the effect of GIP on steroid-hormone secretion in this species are lacking. Hence, we have investigated the distribution of GIP binding sites in the rat adrenal gland and the effect of their activation in vivo and in vitro. Autoradiography evidenced abundant [ 125I]GIP binding sites exclusively in the inner adrenocortical layers, and the computer-assisted densitometric analysis of autoradiograms demonstrated that binding was displaced by cold GIP, but not by either ACTH or the selective ACTH-receptor antagonist corticotropin-inhibiting peptide (CIP). The intraperitoneal (IP) injection of GIP dose-dependently raised corticosterone, but not aldosterone plasma concentration: the maximal effective dose (10 nmol/rat) elicited a twofold increase. GIP did not affect aldosterone and cyclic-AMP release by dispersed zona glomerulosa cells. In contrast, GIP enhanced basal corticosterone secretion and cyclic-AMP release by dispersed inner adrenocortical cells in a concentration-dependent manner, and the maximal effective concentration (10 −7 M) evoked 1.5- and 2.4-fold rises in corticosterone and cyclic-AMP production, respectively. GIP (10 −7 M) did not display any additive or potentiating effect on corticosterone and cyclic-AMP responses to submaximal or maximal effective concentrations of ACTH. The corticosterone secretagogue action of 10 −7 M GIP was abolished by the protein kinase A (PKA) inhibitor H-89 (10 −5 M), and unaffected by CIP (10 −6 M). Collectively, these findings indicate that GIP exerts a moderate but statistically significant stimulatory effect on basal glucocorticoid secretion in rats, acting through specific receptors coupled with the adenylate cyclase/PKA-dependent signaling pathway.

Galanin Stimulates Glucocorticoid Secretion in Rats through a Receptor-dependent Activation of the Adenylate Cyclase/Protein Kinase A-dependent Signaling Pathway

Galanin, a 29-amino acid peptide widely distributed in the central and peripheral nervous systems, was found to induce a concentration-dependent increase in corticosterone secretion and cyclic-AMP release by dispersed rat inner adrenocortical cells (maximal effective concentration, 10 −7M). The effect of 10 −7M galanin was blocked by 10 −6M galantide, a specific antagonist of galanin receptors. Galanin (10 −7M) also enhanced corticosterone and cyclic-AMP responses of dispersed cells to submaximal but not maximal (10 −9M) effective concentrations of ACTH, and again this effect was reversed by galantide. The ACTH-receptor antagonist corticotropin-inhibiting peptide (10 −6M) blocked corticosterone response of dispersed cells to 10 −9M ACTH but not to 10 −7M galanin; conversely, the specific protein kinase A inhibitor H-89 (10 −5M) annulled the secretory response to both ACTH and galanin. In light of these findings, we conclude that galanin stimulates adrenal glucocorticoid secretion in rats, acting through specific receptors, coupled, like those of ACTH, with the adenylate cyclase/protein kinase A-dependent signaling pathway.

The immunomodulator OM-89 induces acth and glucocorticoid secretion in rats through an IL-1 dependent pathway

The immunomodulator OM-89 (bacterial extract from E. coli), known to act on the immune system by modulating both humoral and cellular responses, significantly increases ACTH and glucocorticoids secretion in normal Wistar rats. A comparative administration of IL-1 displays a similar pattern of release. Moreover, OM-89-induced responses are blocked by IL-1ra, the soluble receptor antagonist of IL-1. The effect of OM-89 can thus be explained, at least in part, via IL-1 which directly enhances the secretion of both stress hormones. Finaly, a comparative experiment between control and stressed rats (by immobilization) shows that the responses to OM-89 measured in this study (ACTH and corticosterone secretion) are stress-modulated.

Effect of luteinizing hormone-releasing hormone on rat adrenocortical cells

The effects of luteinizing hormone-releasing hormone (LH-RH) on the function of rat adrenal cortex were investigated by using dispersed zona glomerulosa (capsular) and zona fasciculata-reticularis (inner) cells. LH-RH increased basal (but not adrenocorticotropic hormone (ACTH)-stimulated) corticosterone secretion of inner cells, without affecting either aldosterone or corticosterone production by capsular cells. LH-RH markedly raised basal (but not ACTH-enhanced) cyclic-AMP release by inner cells. The corticosterone secretagogue action of LH-RH was abolished by the protein kinase A inhibitor H-89. The conclusion is drawn that LH-RH specifically stimulates adrenal glucocorticoid secretion in rats through the activation of the adenylate cyclase signaling pathway.

Effect of 5-bromo-2′-deoxyuridine on the proliferative activity of thymus and regenerating adrenal cortex

5-Bromo-2′-deoxyuridine (BrdU) has been recently found to enhance adrenal glucocorticoid secretion in rats. Since BrdU-labeling is today the most employed technique for assessing cell proliferation, we have investigated whether this side-effect of BrdU may influence mitotic activity (as evaluated by metaphase-arrested cell counting) in the thymus cortex and regenerating adrenal cortex. BrdU ( 1 mg 100 g body weight) evoked a 6-fold rise in the blood level of corticosterone in intact rats, but not in animals bearing regenerating adrenals, in which glucocorticoid secretion was very low. Mitotic index in the thymus of intact rats was not changed by BrdU, but it was strongly depressed in regenerating adrenals. These findings rule out the possibility that the glucocorticoid secretagogue action of BrdU exerts a sizable effect on the proliferative activity of both thymus and adrenal cortex. The marked lowering in the mitotic rate in the regenerating adrenal cortices could be ascribed to the well-know differentiation promoting action of BrdU, a finding which, if confirmed, would make highly unreliable the use of BrdU-labeling technique in cultures of adrenocortical cells.

TNF-α facilitates inflammation-induced glucocorticoid secretion in rats with biliary obstruction

Aims: We investigated the role of TNF-α in inflammation-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis in rats with cholestasis due to bile duct resection. Methods: Acute inflammation was induced in bile duct or sham resected rats by subcutaneous injection of carrageenan and HPA axis activation was determined by measuring plasma ACTH and corticosterone levels in the absence or presence of TNF-α inhibition. Results: Bile duct resected rats had a 2.4-fold elevation in basal circulating TNFA-α levels compared to sham resected and unoperated controls. Acute inflammation induced by carrageenan injection resulted in a significant increase in plasma ACTH and corticosterone levels in bile duct resected and control rats in the absence of significant changes in plasma TNF-α levels. However, bile duct resected rats demonstrated blunted ACTH release coupled with augmented corticosterone secretion in response to carrageenan administration compared to control rats. Inhibition of TNF-α activity by pretreating rats with a specific TNF-antiserum or pentoxifylline did not alter inflamamtion-induced ACTH secretion in bile duct resected or control rats, or corticosterone secretion in control rats. However, anti-TNF treatments significantly attenuated the inflammation-induced rise in plasma corticosterone in bile duct resected rats. Conclusions: These results indicate that inflammation in rats with biliary obstruction is associated with blunted ACTH release coupled with augmented glucocorticoid secretion facilitated by TNF-α. Furthermore, these results suggest that what have been previously considered as low level elevations in circulating TNF-α levels can facilitate adrenal glucocorticoid secretion during the inflammatory response.

Thyrotropin-releasing hormone inhibits glucocorticoid secretion of rat adrenal cortex: in vivo and in vitro studies.

The bolus iv administration of TRH dose-dependently decreased ACTH-enhanced plasma corticosterone (B) concentration in rats, without affecting the basal one. The effects of TRH on steroid secretion of dispersed rat inner adrenocortical cells were investigated by HPLC. TRH significantly decreased both basal and ACTH-stimulated post-11-deoxycorticosterone (DOC) secretion (i.e. 18-hydroxy-DOC and B) and concomitantly raised DOC and progesterone release, so that the total postpregnenolone yield of our preparations was unaffected. TRH did not alter either basal or ACTH-stimulated pregnenolone production by isolated rat adrenocortical cells. It was concluded that TRH is an inhibitor of glucocorticoid secretion in rats, which electively impairs the late steps of B synthesis (i.e. 11- and 18-hydroxylation) without affecting the earlier steps, including the rate-limiting one of this process.

Thyrotropin-releasing hormone inhibits glucocorticoid secretion of rat adrenal cortex: in vivo and in vitro studies

The bolus iv administration of TRH dose-dependently decreased ACTH-enhanced plasma corticosterone (B) concentration in rats, without affecting the basal one. The effects of TRH on steroid secretion of dispersed rat inner adrenocortical cells were investigated by HPLC. TRH significantly decreased both basal and ACTH-stimulated post-11-deoxycorticosterone (DOC) secretion (i.e. 18-hydroxy-DOC and B) and concomitantly raised DOC and progesterone release, so that the total postpregnenolone yield of our preparations was unaffected. TRH did not alter either basal or ACTH-stimulated pregnenolone production by isolated rat adrenocortical cells. It was concluded that TRH is an inhibitor of glucocorticoid secretion in rats, which electively impairs the late steps of B synthesis (i.e. 11- and 18-hydroxylation) without affecting the earlier steps, including the rate-limiting one of this process.