Maternal adrenocortical hormones maintain the early development of pancreatic B cells in the fetal rat.
To investigate the effect of maternal adrenocortical hormones on the development of fetal pancreatic islet cells, pregnant rats were adrenalectomised on d 6 of gestation. On d 12-16 the growth patterns of fetal insulin-producing B cells, glucagon-producing A cells, and somatostatin-producing D cells were observed histometrically. Maternal adrenalectomy resulted in growth retardation of fetal B cells on d 12-15. Maternal corticosterone therapy prevented this retardation. Maternal adrenalectomy, however, did not affect the developmental patterns of A and D cells. By Western blotting and immunohistochemistry, glucocorticoid receptors were demonstrated to be present in the islet cells from d 12 to d 15. These results suggest that maternal adrenocortical hormones, glucocorticoids in particular, maintain the early development of fetal pancreatic B cells through their specific intracellular glucocorticoid receptor. (+info)
Pharmacodynamic actions of (S)-2-[4,5-dihydro-5-propyl-2-(3H)-furylidene]-1,3-cyclopentanedione (oudenone).
The pharmacodynamic actions of (S)-2-[4,5-dihydro-5-propyl-2(3H)-furylidene]-1,3-cyclopentanedione (oudenone) were studied in both anesthetized animals and isolated organs. Oudenone (10--40 mg/kg i.v.) induced an initial rise in blood pressure followed by a prolonged hypotension in the anesthetized rats. In unanesthetized spontaneously hypertensive rats (SHR), oudenone (5--200 mg/kg p.o.) caused a dose-related decrease in the systolic blood pressure. The initial pressor effect was diminished by pretreatments with phentolamine, guanethidine, hexamethonium and was abolished in the pithed rats. In addition, intracisternal administrations of oudenone (100--600 mug/kg) showed a marked increase in blood pressure in the anesthetized rats, suggesting that the pressor effect may be due to centrally mediated actions. Oudenone, given intra-arterially into the femoral artery (400--800 mug/kg), caused a long-lasting vasodilation in anesthetized dogs. At a relatively high dose (40 mg/kg i.v.), oudenone antagonized all pressor responses to autonomic agents and central vagus nerve stimulation in anesthetized rats and dogs, however, oudenone showed no anti-cholinergic,-histaminergic, beta-adrenergic and adrenergic neuron blocking properties. (+info)
Primary aldosteronism with aldosterone-producing adrenal adenoma in a pregnant woman.
A 30-year-old pregnant woman complained of muscle weakness at 29 weeks' gestation. She was hypertensive with severe hypokalemia. Lower plasma renin activity and higher aldosterone level than the normal values in pregnancy suggested primary aldosteronism. A cesarean delivery was performed at 31 weeks' gestation because of pulmonary congestion. The neonatal course was uncomplicated. The laparoscopic adrenalectomy for a 2.0-cm right adrenal adenoma resulted in normalizing of her blood pressure and serum potassium level. Although primary aldosteronism is rare, especially during pregnancy, it should be always considered as one of etiologies of hypertension in pregnancy. (+info)
Activation of the adult mode of ovine growth hormone receptor gene expression by cortisol during late fetal development.
The developmental and tissue-specific regulation of growth hormone receptor (GHR) mRNA expression is complex and involves alternate leader exon usage. The transcript composition of hepatic GHR mRNA has therefore been determined in fetal sheep during late gestation and after experimental manipulation of fetal plasma cortisol levels by fetal adrenalectomy and exogenous cortisol infusion, using RNase protection assays and a riboprobe containing exons 1A, 2, and 3 of the ovine GHR gene. Expression of the adult liver-specific GHR mRNA transcript containing exon 1A was not detected earlier than 138 days of gestation (term 145 +/-2 days). Thereafter, expression of this leader exon increased and accounted for 25-30% of the total GHR mRNA in the fetal liver at term. Hepatic GHR mRNA derived from leader exons other than 1A was detectable at 97 days and increased in abundance toward term in parallel with the normal prepartum rise in fetal plasma cortisol. Abolition of this cortisol surge by fetal adrenalectomy prevented both the activation of exon 1A expression and the prepartum rise in GHR mRNA derived from the other leader exons in fetal ovine liver. Conversely, raising cortisol levels by exogenous infusion earlier in gestation prematurely activated exon 1A expression and enhanced the abundance of GHR mRNA transcripts derived from the other leader exons. Cortisol therefore appears to activate the adult mode of GHR gene expression in fetal ovine liver during late gestation. These observations have important implications for the maturation of the somatotrophic axis and for the onset of GH-dependent growth after birth. (+info)
Glucocorticoid enhances interleukin-1-induced pressor response in freely moving rats through its effect on nitric oxide release.
We investigated whether changes in nitric oxide (NO) release might be responsible for the modulation by glucocorticoids of the pressor response to i.p. injection of interleukin-1beta (IL-1beta) in freely moving rats. In such rats, IL-1beta (10 microgram/kg) induced a biphasic pressor response, with a rise in the plasma concentration of NOx (NO2(-) and NO3(-): metabolites of NO) during the second phase. Systemic pretreatment with an exogenous glucocorticoid, dexamethasone (0.5 mg/kg), enhanced the second phase of the pressor response and completely suppressed the increase in plasma NOx. Treatment with Nomega-nitro-L-arginine methyl ester (L-NAME, a nonspecific NO synthase inhibitor), enhanced the pressor response while attenuating the increase in plasma NOx. After bilateral adrenalectomy, IL-1beta induced a smaller pressor response, but a larger increase in plasma NOx; dexamethasone reversed these changes. Our results suggest that endogenous NO moderates the pressor response to IL-1beta in freely moving rats, and that glucocorticoids enhance the IL-1beta-induced pressor response at least in part by reducing endogenous NO release. (+info)
Endogenous glucocorticoids protect against cytokine-mediated lethality during viral infection.
Certain cytokines activate the hypothalamic-pituitary-adrenal axis for glucocorticoid release, and these hormones can protect against cytokine-mediated pathologies. However, endogenous activation of such a pathway has not been established during infections. A prominent glucocorticoid response peaks 36 h following murine CMV (MCMV) infection, coincident with circulating levels of the cytokines IL-12, IFN-gamma, TNF, and IL-6, and dependent on IL-6 for maximal release. These studies examined functions of the hormone induction. Mice rendered glucocorticoid deficient by adrenalectomy were more susceptible than intact mice to MCMV-induced lethality, and the increased sensitivity was reversed by hormone replacement. Lack of endogenous glucocorticoids resulted in increases in IL-12, IFN-gamma, TNF, and IL-6 production, as well as in mRNA expression for a wider range of cytokines, also including IL-1 alpha and IL-1 beta. Viral burdens did not increase, and actually decreased, in the livers of glucocorticoid-deficient mice. TNF, but not IFN-gamma, was required for increased lethality in the absence of endogenous hormone. These results conclusively demonstrate the importance of induced endogenous glucocorticoids in protection against life-threatening effects resulting from infection-elicited cytokine responses. Taken together with the dependence on induced IL-6, they document existence of an immune system-hypothalamic-pituitary-adrenal axis pathway for regulating endogenous responses to viral infections. (+info)
Mechanisms underlying the anti-inflammatory actions of central corticotropin-releasing factor.
Immune activation of hypothalamic corticotropin-releasing factor (CRF) provides a negative feedback mechanism to modulate peripheral inflammatory responses. We investigated whether central CRF attenuates endothelial expression of intercellular adhesion molecule 1 (ICAM-1) and leukocyte recruitment during endotoxemia in rats and determined its mechanisms of action. As measured by intravital microscopy, lipopolysaccharide (LPS) induced a dose-dependent increase in leukocyte rolling, adhesion, and emigration in mesenteric venules, which was associated with upregulation of endothelial ICAM-1 expression. Intracisternal injection of CRF abrogated both the increased expression of ICAM-1 and leukocyte recruitment. Intravenous injection of the specific CRF receptor antagonist astressin did not modify leukocyte-endothelial cell interactions induced by a high dose of LPS but enhanced leukocyte adhesion induced by a low dose. Blockade of endogenous glucocorticoids but not alpha-melanocyte-stimulating hormone (alpha-MSH) receptors reversed the inhibitory action of CRF on leukocyte-endothelial cell interactions during endotoxemia. In conclusion, cerebral CRF blunts endothelial upregulation of ICAM-1 and attenuates the recruitment of leukocytes during endotoxemia. The anti-inflammatory effects of CRF are mediated by adrenocortical activation and additional mechanisms independent of alpha-MSH. (+info)
Fetal rat adrenal steroidogenesis and steroid transfer to adrenalectomized mother.
On the 22nd day of gestation in rats, fetuses of acutely adrenalectomized mothers were injected subcutaneously with 0.43 muCi 4-14C-progesterone in 0.05 ml saline. Ten and 20 min after injection to fetuses, samples were taken to determine the 14C-progesterone metabolites in the plasma and adrenal glands. After extraction of the samples taken, the metabolites were separated by two-dimensional thin-layer chromatography and identified by autoradiography. 11-deoxycorticosterone, 18-hydroxy-11-deoxycorticosterone, corticosterone and 11beta-hydroxyprogesterone were identified in the plasma of injected fetuses, and, in far smaller amounts, in the plasma of their mothers. The plasma of noninjected fetuses also contained very small amounts of these corticoids. The fetal adrenal glands contained far smaller amounts of radioactive steroids than the fetal plasma did. The results obtained show that steroids of fetal origin can cross the placenta in and out, constituting evidence that the fetal adrenal glands are the only source of the plasma corticoids of their adrenalectomized mothers. (+info)