CRH mRNA expression in the hypothalamic paraventricular nucleus is inhibited despite the activation of the hypothalamo-pituitary-adrenal axis during starvation.

Corticotropin-releasing hormone (CRH) is one of the anorexigenic neuropeptides, and indeed the expression of hypothalamic CRH is known to be inhibited by starvation. To clarify whether elevated plasma glucocorticoid during starvation is responsible for the CRH suppression, we examined the expression level of hypothalamic CRH mRNA after food deprivation in adrenalectomized, plasma corticosterone (B)-clamped animals. Male Wistar rats were divided into 2 groups: one group had adrenalectomy (ADX) and B pellet implantation (ADX+B, n=42), and the other group had only sham operation (sham, n=42). Rats were then treated with either ad libitum food supply or food deprivation for up to 96 h. The expression of CRH mRNA in the paraventricular nucleus (PVN) was estimated by in situ hybridization. After food deprivation, mean plasma B level was markedly elevated in sham group, but almost clamped in the ADX+B group. In this experimental condition, CRH mRNA in the PVN was significantly decreased in the sham group, whereas no change was obtained in the ADX+B group. Our data suggest the decrease in CRH mRNA seems to be related to the elevated glucocorticoid level during starvation. The status of hyperadrenocorticism without activation of CRH led us to speculate that adrenocortical function is predominant in the hypothalamic-pituitary-adrenal (HPA) axis during starvation.

The roles of corticotropin-releasing factor-related peptides and their receptors in the cardiovascular system.

Corticotropin-releasing factor (CRF), CRF-related peptides and their receptors are present in the central nervous system and in peripheral tissues including the immune, reproductive and cardiovascular systems. CRF and urocortin (urocortin 1) bind to the CRF receptor type 1 (CRF(1) receptor) and the CRF receptor type 2 (CRF(2) receptor), whereas urocortin 2 (formerly known as stresscopin related peptide) and urocortin 3 (formerly known as stresscopin) bind with high affinity to the CRF(2) receptor. Recent studies show that urocortin 1, urocortin 2 and urocortin 3 are potent regulators of cardiovascular function. This review highlights the role of cardiovascular CRF and related peptides and its relevance in mediating the adaptive response of the cardiovascular system to stressful conditions.

Expression of type 1 corticotropin-releasing hormone (CRH) receptor mRNA in the hypothalamic paraventricular nucleus following restraint stress in CRH-deficient mice.

Previous studies have demonstrated that various types of stress increase type 1 corticotropin-releasing hormone (CRH) receptor (currently abbreviated to CRF1 receptor) mRNA in the hypothalamic paraventricular nucleus (PVN) of rats, but not mice. This study investigated whether different sensitivities of glucocorticoid-mediated negative feedback effects can explain this species difference in stress-induced PVN CRF1 receptor mRNA expression. First, the CRF1 receptor mRNA level in the PVN of CRH knockout (KO) mice during acute restraint stress was compared with that in wild-type (WT) mice. Consistent with previous findings, WT mice showed no induction of CRF1 receptor mRNA in the PVN following acute restraint, regardless of normal hypothalamic-pituitary-adrenocortical responses. In contrast, CRF1 receptor mRNA in the PVN of CRH KO mice was increased following 2 h of restraint. Since the response of tyrosine hydroxylase (TH) mRNA in the locus coeruleus (LC) to restraint was similar between CRH KO and WT mice, it is unlikely that enhanced noradrenergic input into the PVN was responsible for the CRF1 receptor mRNA induction in CRH KO mice. Second, to determine whether CRH KO per se or a low corticosterone response to stress is required to induce CRF1 receptor mRNA expression in the PVN in mice, the response of adrenalectomized WT mice was examined. Acute restraint increased the CRF1 receptor mRNA level in the PVN of adrenalectomized WT mice, similar to the case for CRH KO mice. TH mRNA in the LC showed similar increases in sham and adrenalectomized WT mice. These results indicate that PVN CRF1 receptor mRNA is much more sensitive to glucocorticoid-mediated negative feedback in mice than in rats, such that a normal increase in plasma corticosterone during stress can mask CRF1 receptor mRNA induction in the PVN of mice.

Exposure to the environmental estrogen bisphenol A differentially modulated estrogen receptor-alpha and -beta immunoreactivity and mRNA in male mouse testis.

We examined the effects of bisphenol A (0.5 microg/ml or 50 microg/ml) in the drinking water on estrogen receptor (ER) alpha and beta proteins and mRNA in the testis of young mice following 8-weeks of oral administration of bisphenol A utilizing immunohistochemistry and semiquantitative reverse transcription polymerase chain reaction amplification (RT-PCR). ER beta was clearly localized in the nuclei of spermatogonia and/or spermatocytes. ER beta immunopositive cell numbers per testis section were significantly decreased in the 50 microg/ml bisphenol A-treated group compared with control and the 0.5 microg/ml bisphenol A-treated group. The number of ER alpha positive cells in the testis was significantly lower than ER beta positive cells in control group. ER alpha immunopositive cell numbers per testis section were markedly increased in the 50 microg/ml bisphenol A-treated group compared with the control and the 0.5 microg/ml bisphenol A-treated group. ER beta mRNA expression was significantly decreased in the 50 microg/ml bisphenol A-treated group compared with the control and the 0.5 microg/ml bisphenol A-treated group. In contrast, ER alpha mRNA expression was markedly increased in the 50 microg/ml bisphenol A-treated group compared with the control and the 0.5 microg/ml bisphenol A-treated group. The existence of ER alpha and beta in the testis suggests that estrogens directly affect germ cells during testicular development and spermatogenesis, and differential modulation of ER alpha and beta in the testis could be involved in the effects of bisphenol A.

Down-regulation of corticotropin-releasing hormone receptor type 2beta mRNA expression in the rat cardiovascular system following food deprivation.

The present study was conducted to assess the effect of nutritional stress induced by food deprivation on expression of messenger ribonucleic acid (mRNA) for corticotropin-releasing hormone receptor type 2beta (CRH-R2beta) in the rat cardiovascular system in the presence or absence of changes in circulating corticosterone. Food deprivation for 96 h caused a robust increase in plasma corticosterone levels and a significant decrease in CRH-R2beta mRNA expression in the rat heart. Starvation for 48 and 96 h decreased CRH-R2beta mRNA expression in the atria, ventricle as well as aorta of sham-adrenalectomized (sham) rats. Surprisingly, clamping plasma glucocorticoids at low levels by adrenalectomy with corticosterone pellet replacement (ADX+B) did not completely prevent starvation-induced decreases of CRH-R2beta mRNA expression in the rat cardiovascular system. Urocortin (Ucn) mRNA expression was increased significantly by food deprivation in the heart of sham as well as ADX+B rats. We speculate that food deprivation may increase urocortin, which in turn down-regulates CRH-R2beta mRNA expression in cardiovascular system. These data indicate that food deprivation despite the presence or absence of changes in circulating corticosterone may have an inhibitory effect on CRH-R2beta mRNA expression in the rat cardiovascular system.