1,720,974 research outputs found
PANCREATIC-POLYPEPTIDE STIMULATES CORTICOSTERONE SECRETION BY ISOLATED RAT ADRENOCORTICAL-CELLS
No full textPancreatic polypeptide (PP) dose-dependently enhanced both basal and submaximally ACTH-stimulated corticosterone production by dispersed zona fasciculata/reticularis cells of the rat adrenal gland. Conversely PP did not affect either basal or ACTH- and angiotensin-II-stimulated aldosterone and corticosterone secretion of zona glomerulosa cells. These findings could throw light on the physiological significance of the marked increase in the pancreatic release of PP during stresses
Effects of glucagon and glucagon-like peptide-1 on glucocorticoid secretion of dispersed rat adrenocortical cells.
No full textThe effects of glucagon and glucagon-like peptide-1 (GLP-1) on the secretory activity of rat adrenocortical cells have been investigated in vitro. Neither hormones affected basal or agonist-stimulated aldosterone secretion of dispersed rat zona glomerulosa cells or basal corticosterone production of zona fasciculata-reticularis (inner) cells. In contrast, glucagon and GLP-1 partially (40%) inhibited ACTH (10(-9) M)-enhanced corticosterone secretion of inner cells, maximal effective concentration being 10(-7) M. The effect of 10(-7) M glucagon or GPL-1 was suppressed by 10(-6) M Des-His1-[Glu9]-glucagon amide (glucagon-A) and exendin-4(3-39) (GPL-1-A), which are selective antagonists of glucagon and GLP-1 receptors, respectively. Glucagon and GLP-1 (10(-7) M) decreased by about 45-50% cyclic-AMP production by dispersed inner adrenocortical cells in response to ACTH (10(-9) M), but not to the adenylate cyclase activator forskolin (10(-5) M). Again this effect was blocked by 10(-6) M glucagon-A or GLP-1-A. The exposure of dispersed inner cells to 10(-7) M glucagon plus GLP-1 completely suppressed corticosterone response to ACTH (10(-9) M). However, they only partially inhibited (by about 65-70%) both corticosterone response to forskolin (10(-5) M) or dibutyryl-cyclic-AMP (10(-5) M) and ACTH (10(-9) M)-enhanced cyclic-AMP production. Quantitative HPLC showed that 10(-7) M glucagon or GLP-1 did not affect ACTH-stimulated pregnenolone production, evoked a slight rise in progesterone and 11-deoxycorticosterone release, and markedly reduced (by about 55%) corticosterone secretion of dispersed inner adrenocortical cells. In light of these findings the following conclusion are drawn: (i) glucagon and GLP-1, via the activation of specific receptors, inhibit glucocorticoid response of rat adrenal cortex to ACTH; and (ii) the mechanism underlying the effect of glucagon and GLP-1 is probably two-fold, and involves both the inhibition of the ACTH-induced activation of adenylate cyclase and the impairment of the late steps of glucocorticoid synthesis
Endothelin-1 stimulates steroid secretion of human adrenocortical cells ex vivo via both ETA and ETB receptor subtypes.
No full textEFFECTS OF CYCLOSPORINE-A ON STEROID-SECRETION OF DISPERSED RAT ADRENOCORTICAL-CELLS
Full text linkThe acute effect of cyclosporine-A (CSA), a potent immunosuppressive agent, on the secretory activity of dispersed rat adrenocortical cells was investigated. The production of the following steroid hormones was assayed by high performance liquid chromatography: pregnenolone (PREG), progesterone (PROG), 11-deoxycorticosterone (DOC), corticosterone (B), 18-hydroxy-11-deoxycorticosterone (18OH-DOC), 18-hydroxycorticosterone (18OH-B) and aldosterone (ALDO); B and ALDO outputs were also measured by radioimmunoassay. Low concentrations of CSA (0.1-0.2 mg/ml) enhanced basal, but not ACTH- or angiotensin-II (ANG-II) 10(-8) M-stimulated, secretions of PREG, non-18-hydroxylated steroids (PROG, DOC and B) and 18-hydroxylated steroids (18OH-DOC, 18OH-B and ALDO) of both zona glomerulosa (ZG) and zonae fasciculata and reticularis (ZF/ZR) cells. Middle concentrations of CSA (from 0.3 to 0.5 mg/ml) did not affect PREG yield, nor did they alter basal and ACTH-stimulated post-PREG output of both ZG and ZF/ZR cells; however, they elicited a marked decrease in ANG-II-enhanced production of 18-hydroxylated steroid by AG cells. Concentrations of CSA higher than 0.5 mg/ml strikingly reduced either basal and agonist-stimulated over-all steroidogenesis of both ZG and ZF/ZR cells. These findings suggest that CSA at low concentrations strongly stimulates the conversion of cholesterol to PREG (i.e. the rate-limiting step of steroidogenesis), while at middle concentrations it did not affect this early step, but specifically interferes with the intracellular events which transduce the stimulatory signal of ANG-II on the late steps of mineralocorticoid production (i.e. the conversion of B to ALDO). At higher concentrations, CSA probably exerts a cytotoxic effect
EFFECTS OF PROLONGED SODIUM RESTRICTION ON THE MORPHOLOGY AND FUNCTION OF RAT ADRENOCORTICAL AUTOTRANSPLANTS
No full textRegenerated adrenocortical nodules were obtained by implanting fragments of the capsular tissue of excised adrenal glands into the musculus gracilis of rats (Belloni et al. 1990). Five months after the operation, operated rats showed a normal basal blood level of corticosterone, but a very low concentration of circulating aldosterone associated with a slightly increased plasma renin activity (PRA). Regenerated nodules were well encapsulated and some septa extended into the parenchyma from the connective-tissue capsule. The majority of parenchymal cells were similar to those of the zonae fasciculata and reticularis of the normal adrenal gland, while zona glomerulosa-like cells were exclusively located around septa (juxta-septal zone; JZ). In vitro studies demonstrated that nodules were functioning as far as glucocorticoid production was concerned, while mineralocorticoid yield was very low. Prolonged sodium restriction significantly increased PRA and plasma aldosterone concentration, and provoked a marked hypertrophy of JZ, which was due to increases in both the number and average volume of JZ cells. Accordingly, the in vitro basal production of aldosterone and other 18-hydroxylated steroids was notably enhanced. The plasma level of corticosterone, as well as zona fasciculata/reticularis-like cells and in vitro production of glucocorticoids by regenerated nodules were not affected. These findings, indicating that autotransplanted adrenocortical nodules respond to a prolonged sodium restriction similar to the normal adrenal glands, suggest that the relative deficit in mineralocorticoid production is not due to an intrinsic defect of the zona glomerulosa-like JZ, but is probably caused by the impairment of its adequate stimulation under basal conditions.(ABSTRACT TRUNCATED AT 250 WORDS
EFFECTS OF INTERLEUKIN-1-BETA ON STEROIDOGENESIS IN LEYDIG-CELLS OF THE RAT TESTIS - IN-VIVO AND IN-VITRO STUDIES
No full textThe effects of interleukin-1β (IL-1β) on the secretory activity of Leydig cells were investigated in hypophysectomized/human chorionic gonadotropin (hCG)-treated rats. IL-1β dose-dependently increased basal and hCG-stimulated plasma testosterone concentration (PTC) and testosterone secretion by isolated Leydig cells. Basal PTC returned to the control level 12 h after the injection of a maximal effective dose of IL-1β (10 nmol/rat), but after 24 and 36 h it was markedly lower than in control animals; after 48 h PTC again attained the control value. IL-1β did not affect basal PTC in rats injected 24 h before with 10 nmol of IL-1β (IL-1β-pretreated rats), but it dose-dependently decreased hCG-stimulated PTC. However, IL-1β dose-dependently enhanced both basal and hCG-stimulated testosterone production by dispersed Leydig cells obtained from IL-1β-pretreated rats. Corticotropin-releasing hormone (CRH) concentration was very low in the testes of control rats, but it did display a striking rise 24 h after the injection of IL-1β. As expected, CRH (100 pmol/rat) and IL-1β (10 nmol/rat) elicited a marked decrease in hCG-enhanced PTC in IL-1β-pretreated rats. (a-Helical)-CRH, a competitive inhibitor of CRH, did not alter hCG-stimulated PTC in control IL-1β-pretreated rats, but it did completely annul the inhibitory effect of both CRH and IL-1β. In light of the present findings, it seems reasonable to suggest that IL-1β exerts a two-fold modulatory action on rat testis steroidogenesis: IL-1β (i) acutely stimulates testosterone secretion by acting directly on Leydig cells, and (ii) induces the intratesticular production of CRH, which in turn inhibits Leydig-cell secretory activity. This last effect, however, requires 24 h to become manifest, since it probably involves the de novo expression of CRH gene
Endothelin adrenocortical secretagogue effect is mediated by the B receptor in rats
No full textWe investigated the gene expression and localization of endothelin-1 (ET-1) receptor subtypes ET(A) and ET(B) in the rat adrenal cortex as well as their involvement in the corticosteroid secretagogue effect of ET-1 in vitro. Reverse transcription-polymerase chain reaction with primers specific for ET(A) and ET(B) cDNAs demonstrated the expression of both receptor genes in homogenates of adrenocortical tissue. However, in isolated zona glomerulosa and zona fasciculata cells, only ET(B) mRNA was detected. Autoradiographic examination of the selective displacement of 125I-ET-1 binding by BQ-123 and BQ-788 (specific ligands for ET(A) and ET(B), respectively) indicated that zona glomerulosa possesses both ET(A) and ET(B), whereas zona fasciculata is exclusively provided with ET(B). ET-1 enhanced in a concentration-dependent manner aldosterone and corticosterone secretions of dispersed zona glomerulosa and zona fasciculata cells, respectively. The ET(B) antagonist BQ-788 markedly reduced the secretory response of zona glomerulosa cells and completely suppressed that of zona fasciculata cells, whereas the ET(A) antagonist BQ-123 was ineffective. These findings indicate that in the rat, the adrenocortical secretagogue action of ET-1 is mediated by the ET(B) receptor subtype and that the ET(A) receptor is not directly involved in such an effect
NEUROPEPTIDE-K ENHANCES GLUCOCORTICOID RELEASE BY ACTING DIRECTLY ON THE RAT ADRENAL-GLAND - THE POSSIBLE INVOLVEMENT OF ZONA MEDULLARIS
No full textNeuropeptide K (NPK), a member of the kassinin-like tachykinin family, is contained in the rat hypothalamus and is known to stimulate pituitary ACTH release. The intraperitoneal bolus administration of NPK dose-dependently enhanced corticosterone blood level not only in intact rats, but also in hypophysectomized/ACTH replaced animals. NPK did not affect corticosterone secretion of dispersed rat adrenocortical cells; however, it concentration-dependently raised basal corticosterone production by decapsulated adrenal quarters (including both cortical and medullary tissues). Minimal and maximal effective concentrations were 10(-9) and 10(-8) M, respectively. 10(-8) M NPK potentiated corticosterone response of adrenal quarters elicited by 10(-12) M ACTH, but not that evoked by higher concentrations of ACTH. The direct corticosterone secretagogue effect of 10(-8) M NPK is annulled by 10(-6) M alpha-helical-CRH or corticotropin-inhibiting peptide, competitive inhibitors of CRH and ACTH, respectively. In light of these findings, the hypothesis is advanced that NPK exerts a direct stimulatory action on adrenocortical secretion and that the mechanism underlying this effect of NPK may involve the activation of the intra-medullary CRH/ACTH system
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