Carey M P, Deterd C H, de Koning J, Helmerhorst F, de Kloet E R
Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University, The Netherlands.
J Endocrinol. 1995 Feb;144(2):311-21. doi: 10.1677/joe.0.1440311.
The present study examined the association between hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-ovarian axes. HPA activity determined by plasma levels of adrenocorticotropin (ACTH) and corticosterone (B) was assessed in intact female rats as a function of oestrous cycle stage under resting conditions and after exposure to a 20 min restraint stress. To delineate the roles of oestradiol and progesterone in HPA axis modulation, plasma concentrations of ACTH and B were determined in ovariectomised (OVX) animals treated with oestradiol and/or progesterone under resting conditions and during exposure to the stress of a novel environment. The effects of these steroid treatments on the transcription and/or binding properties of the two corticosteroid receptors, the mineralocorticoid (MR) and glucocorticoid (GR) receptors, were also examined in hippocampal tissue, (i) Fluctuations in basal and stress-induced plasma ACTH and B concentrations were found during the oestrous cycle with highest levels at late pro-oestrus. (ii) In OVX steroid-replaced animals, basal and stress-induced activity was enhanced in oestradiol and oestradiol plus progesterone-treated animals compared with OVX controls. (iii) Cytosol binding assays revealed an oestradiol-induced decrease in hippocampal MR capacity. This decrease appears to be due to an effect of the steroid on MR transcription as in situ hybridisation analysis of MR mRNA showed an oestradiol-induced decrease in MR transcript in all hippocampal subfields. (iv) Treatment of oestradiol-primed animals with progesterone reversed the oestradiol-induced decrease in hippocampal MR capacity. Data from MR mRNA hybridisation in situ experiments indicate that this reversal may be due to an antagonism of the oestradiol effect on MR transcription. (v) Progesterone treatment with or without prior oestradiol-priming induced a significant decrease in the apparent binding affinity of hippocampal MR. We show that progesterone and its 11 beta-hydroxylated derivative have a high affinity for the hippocampal MR. (vi) Neither oestradiol nor progesterone affected GR binding parameters in the hippocampus. In conclusion, we find that sex steroids modulate HPA activity and suggest that the observed effects of these steroids on hippocampal MR may underlie their concerted mechanism of action in inducing an enhanced activity at the period of late pro-oestrus.
本研究检测了下丘脑 - 垂体 - 肾上腺（HPA）轴与下丘脑 - 垂体 - 卵巢轴之间的关联。在静息条件下以及暴露于20分钟束缚应激后，根据动情周期阶段，对完整雌性大鼠中由促肾上腺皮质激素（ACTH）和皮质酮（B）的血浆水平所确定的HPA活性进行了评估。为了阐明雌二醇和孕酮在HPA轴调节中的作用，在静息条件下以及暴露于新环境应激期间，对用雌二醇和/或孕酮处理的去卵巢（OVX）动物测定了ACTH和B的血浆浓度。还在海马组织中检测了这些类固醇处理对两种皮质类固醇受体，即盐皮质激素（MR）和糖皮质激素（GR）受体的转录和/或结合特性的影响。（i）在动情周期期间发现基础和应激诱导的血浆ACTH和B浓度存在波动，在发情后期水平最高。（ii）在OVX类固醇替代动物中，与OVX对照组相比，雌二醇和雌二醇加孕酮处理的动物的基础和应激诱导活性增强。（iii）胞浆结合试验显示雌二醇诱导海马MR容量降低。这种降低似乎是由于类固醇对MR转录的影响，因为MR mRNA的原位杂交分析显示在所有海马亚区中雌二醇诱导MR转录物减少。（iv）用孕酮处理经雌二醇预处理的动物可逆转雌二醇诱导的海马MR容量降低。来自MR mRNA原位杂交实验的数据表明这种逆转可能是由于雌二醇对MR转录的作用受到拮抗。（v）有或没有预先雌二醇预处理的孕酮处理均导致海马MR的表观结合亲和力显著降低。我们表明孕酮及其11β - 羟基化衍生物对海马MR具有高亲和力。（vi）雌二醇和孕酮均未影响海马中的GR结合参数。总之，我们发现性类固醇调节HPA活性，并表明这些类固醇对海马MR的观察到的影响可能是它们在发情后期诱导增强活性的协同作用机制的基础。
