过渡到更年期的特点是情绪,行为和代谢变化。然而,对肾上腺对应激反应的变化知之甚少。
这项研究的目的是评估,在4-乙烯基环己烯二环氧化物(VCD)诱导的围绝经期动物模型中,(1)急性束缚应激反应的内分泌和神经元应激系统活动;(2)激素治疗在这种反应中的作用。
青春期前雌性Wistar大鼠每天接受注射(s。c)油或VCD(160mg/kg)15天。治疗开始后第56-66天,受压力的组接受了含有安慰剂(PL)的s.c植入物,17β-雌二醇(E2),孕酮(P4),或E2P4。VCD/油注射后80±5天,施加应力30分钟。在应激反应结束后和结束后60分钟从尾部尖端收集血样,然后用4%的PFA经心脏灌注,以评估c-Fos在室旁核(PVN)和c-Fos/酪氨酸羟化酶(LC)的内侧和后部小细胞(PaMP和PaPo)细分中的表达。对照组没有压力,也没有接受激素治疗。
虽然VCD-围绝经期大鼠和对照大鼠的基础皮质酮水平相似,VCD组的应激反应分泌较低。P4治疗阻止了这种作用。相反,VCD-围绝经期大鼠的P4基础水平低于对照组,两组对压力的反应没有差异。不出所料,在对照和VCD围绝经期大鼠中研究的所有大脑区域中,30分钟的束缚应激都会增加c-Fos免疫反应性。然而,PaMP区域的c-Fos增加减弱。在所有检查的领域,在激素治疗中,c-Fos阳性神经元的数量没有显著差异.
这是第一个在围绝经期大鼠模型中证明生殖衰老伴随着与PVNPaMP区域低活化相关的急性应激反应的皮质酮分泌不足的研究。而肾上腺P4反应被保留。此外,P4治疗被证明可以减轻压力期间进行性卵巢功能衰竭对肾上腺功能的影响。
The transition to menopause is characterized by mood, behavioral and metabolic changes. However, little is known about the changes in adrenal response to stress.
The aim of the study was to evaluate, in an animal model of perimenopause induced by 4-vinylcyclohexene diepoxide (VCD), (1) the endocrine and neuronal stress system activity in response to acute restraint stress and (2) the effect of hormonal therapy in this response.
Prepubertal female Wistar rats received daily injections (s.c) of oil or VCD (160 mg/kg) for 15 days. On 56th-66th days after treatment onset, the groups to be stressed received s.c implants containing placebo (PL), 17β-estradiol (E2), progesterone (P4), or E2P4. At 80 ± 5 days after VCD/oil injections, stress was applied for 30 min. Blood samples were collected immediately after and 60 min after the end of stress session from the tail tip followed by transcardial perfusion with PFA 4% for the assessment of c-Fos expression in the medial and posterior parvocellular (PaMP and PaPo) subdivisions of the paraventricular nucleus (PVN) and c-Fos/tyrosine hydroxylase in the locus coeruleus (LC) using immunohistochemistry. Control groups were not stressed nor received hormone therapy.
While basal corticosterone levels were similar between VCD-periestropausal and control rats, the secretion in response to stress in the VCD group was lower. This effect was prevented by P4 therapy. Inversely, basal levels of P4 were lower in VCD-periestropausal rats than in the controls, and no differences were found in response to stress between the groups. As expected, 30-min restraint stress increased c-Fos immunoreactivity in all brain areas studied in both control and VCD-periestropausal rats. However, the c-Fos increase in the PaMP region was attenuated. In all areas examined, there were no significant differences in the number of c-Fos-positive neurons across hormonal therapies.
This is the first study to demonstrate in a perimenopausal rat model that reproductive aging is accompanied by inadequate secretion of corticosterone in response to acute stress in association with the hypoactivation of the PaMP region of the PVN, while adrenal P4 response is preserved. Moreover, P4 therapy was shown to attenuate the effects of progressive ovarian failure on adrenal functioning during stress.