Androgen regulation of corticotropin-releasing hormone receptor 2 (CRHR2) mRNA expression and receptor binding in the rat brain

Stress-induced affective disorders, such as depression and anxiety, are more prevalent in females than in males. The reduced vulnerability to these disorders in males may be due to the presence of androgens, which are known to dampen the stress response and reduce anxiety-like behaviors. However, a neurobiological mechanism for this sex difference has yet to be elucidated. Corticotropin-releasing hormone receptor 2 (CRHR2) has been implicated in regulating anxiety-type behaviors and is expressed in stress-responsive brain regions that also contain androgen receptors (AR). We hypothesized that androgen may exert its effects through actions on CRHR2 and we therefore examined the regulation of CRHR2 mRNA and receptor binding in the male rat forebrain following androgen administration. Young adult male Sprague/Dawley rats were gonadectomized (GDX) and treated with the non-aromatizable androgen, dihydrotestosterone propionate (DHTP) using hormone filled Silastic capsules. Control animals received empty capsules. Using quantitative real-time RT-PCR, CRHR2 mRNA levels were determined in block-dissected brain regions. DHTP treatment significantly increased CRHR2 mRNA expression in the hippocampus, hypothalamus, and lateral septum (p < 0.01) when compared to vehicle-treated controls. A similar trend was observed in amygdala (p =  0.05). Furthermore, in vitro autoradiography revealed significantly higher CRHR2 binding in the lateral septum in androgen-treated males, with the highest difference observed in the ventral lateral region. Regulation of CRHR2 mRNA by AR was also examined using an in vitro approach. Hippocampal neurons, which contain high levels of AR, were harvested from E17-18 rat fetuses, and maintained in primary culture for 14 days. Neurons were then treated with dihydrotestosterone (DHT; 1 nM), DHT plus flutamide (an androgen receptor antagonist), or vehicle for 48 h. CRHR2 mRNA levels were measured using quantitative real-time RT-PCR. Consistent with in vivo studies, DHT significantly increased CRHR2 mRNA expression in hippocampal neurons (p < .02) compared to vehicle-treated controls. Flutamide treatment prevented the effect of DHT on CRHR2 mRNA indicating that DHT's effect on CRHR2 expression is AR-mediated. Thus, the CRHR2 gene appears to be a target for regulation by AR and these data suggest a potential mechanism by which androgen may alter mood and anxiety-related behaviors.     

Corticotropin-releasing factor receptors in the dorsal raphe nucleus modulate social behavior in Syrian hamsters

Rationale In Syrian hamsters (Mesocricetus auratus), social defeat produces a prolonged change in subsequent agonistic behavior termed conditioned defeat. This stress-induced change in behavior is marked by increased submissive and defensive behavior toward a novel, nonaggressive opponent and a complete loss of normal territorial aggression. Corticotropin-releasing factor (CRF) has been shown to affect serotonergic neurons in the dorsal raphe nucleus (DRN) and to modulate learned helplessness via a CRF type-2 receptor (CRF-R2) mechanism. Objectives In this study, we tested the hypothesis that a nonselective CRF receptor antagonist (experiment 1: 250 or 500 ng d-Phe CRF in 200 nl saline), or a selective CRF-R2 antagonist (experiment 2: 500 ng anti-Svg-30 in 200 nl saline), injected into the DRN would reduce the acquisition of conditioned defeat in male hamsters. We also tested similar hypotheses for the expression of conditioned defeat (experiments 3 and 4). Results Infusion of d-Phe CRF into the DRN significantly reduced both the acquisition and expression of conditioned defeat compared to vehicle controls, whereas infusion of anti-Svg-30 into the DRN reduced expression but not acquisition. In particular, CRF antagonism in the DRN decreased fleeing from novel opponents but did not reinstate normal territorial aggression after social defeat. Conclusions Our results suggest that the increased flight associated with conditioned defeat is modulated by CRF-R2 activation within the DRN. Overall, social defeat is an ethologically relevant stressor that appears to activate at least some of the same neural substrates that have been implicated in the control of learned helplessness.     

Noise stress changes mRNA expressions of corticotropin-releasing hormone,its receptors in amygdala,and anxiety-related behaviors

Noise is a psychological, environmental stressor that activates limbic sites in the brain. Limbic sites such as the amygdala and the amygdaloid corticotropin-releasing hormone (CRH) system play an important role in integrating stress response. We investigated the association between noise exposures, CRH-related molecules in the amygdala, and behavioral alterations. In total 54 Sprague-Dawley rats were divided into the following three groups: Control (CON), acute noise exposure (ANE), and chronic noise exposure (CNE). The ANE group was exposed to 100 dB white noise only once in 4 h and the CNE group was exposed to the same for 4 h per day for 30 days. Expression profiles of CRH and its receptors CRH-R1 and CRH-R2 were analyzed by quantitative real-time polymerase chain reaction (qPCR). The same stress procedure was applied to the ANE and CNE groups for behavior testing. The anxiety responses of the animals after acute and chronic stress exposure were measured in the defensive withdrawal test. CNE upregulated CRH and CRH-R1 mRNA levels but downregulated CRH-R2 mRNA levels. ANE led to a decrease in both CRH-R1 and CRH-R2 expression. In the defensive withdrawal test, while the ANE increased, CNE reduced anxiety-like behaviors. The present study shows that the exposure of rats to white noise (100 dB) leads to behavioral alterations and molecule-specific changes in the CRH system. Behavioral alterations can be related to these molecular changes in the amygdala.     

CRH在感染性早产胎盘滋养细胞中的表达

目的　了解CRH在感染性早产胎盘滋养细胞中的表达情况。方法　筛选 95例胎盘组织 ,分成 4组 :感染性早产组 3 5例 ;早产无感染组 2 0例 ;足月感染组 2 0例 ;足月无感染组 2 0例。免疫组化检测CRH在胎盘滋养细胞中的表达情况。结果　各组胎盘滋养细胞均呈阳性表达 ,以早产无感染组CRH表达最高 ,与其它 3组比较有显著性差异 (P<0 0 0 1) ;感染性早产组与足月感染组及足月无感染组比较无显著性差异 (P >0 0 5 )。在感染性早产组中 ,胎盘CRH的表达强度随炎症程度的加重而降低 ,胎盘滋养细胞CRH表达在轻度组高于中、重度组 (P <0 0 0 1) ,而中度与重度组比较无统计学差异 (P >0 0 5 )。结论　CRH可能更主要与非感染性早产中精神紧张、压抑及疲劳等因素影响神经内分泌失调有关 ,而对感染性早产的预测应用价值受到一定影响。