促肾上腺皮质激素释放激素对生殖细胞的调节作用

综述了促肾上腺皮质激素释放激素调节生殖功能的新进展,内容包括这种在下丘脑、垂体和性腺水平上生殖功能的一系列实验证据。作者认为在今后关于这种激素影响生殖功能的研究中,阐明它调节生殖功能的外周机制当是不容忽视的课题。     

季节性变化对雌性恒河猴生殖功能的影响

目的　研究季节性变化对雌性恒河猴生殖功能的影响。方法　采用随机抽样法和放射免疫测定法 ,分析了不同时期雌性恒河猴性皮肤变化、月经周期和生殖激素变化的特点。结果　 ( 1)性征的季节性变化 :在生殖季节雌性恒河猴几乎都出现性皮肤反应 ,出现比较规则月经周期 ,在非生殖季节只有部分雌性恒河猴出现性皮肤反应 ,月经周期不规则 ,行经频率低 ,有的出现长时间的闭经 ;( 2 )生殖激素的季节性变化 :在生殖季节促性腺激素和性类固醇激素的分泌水平都出现周期性的变化 ,而非生殖季节促性腺激素和性类固醇激素的分泌水平没有显著的差异。结论　雌性恒河猴性皮肤变化、月经周期和生殖激素存在明显的季节性差异 ,这种差异导致了雌性恒河猴生殖功能的季节性变化     

Nesfatin-1与生殖

Nesfatin-1是一种下丘脑神经肽,具有抑制摄食的功能。而能量平衡与生殖功能密切相关,近来研究表明Nesfatin-1参与生殖。本文综述了Nesfatin-1的结构、分布及其在调节促性腺激素分泌、初情期启动和胚胎发育等方面的作用,为进一步研究Nesfatin-1对生殖的影响提供依据。     

神经内分泌因子调控鱼类生殖和生长的相互作用

脊椎动物的生长与生殖活动有着密切的联系并相互作用。许多调节生长和代谢活动的内分泌因子对青春期或者性腺的发育产生影响。同样,调节生殖活动的许多激素亦同时对生长和代谢产生影响。近年来,我们和其他学者对鱼类生长和生殖的神经内分泌调节的相互作用进行了研究,主要的进展是：①在促进性腺的激素影响生长方面,发现促性腺激素释放激素（ＧｎＲＨ）和多巴胺都能和脑垂体生长激素细胞的特异性受体结合而刺激生长激素释放,并能     

中国科学院动物研究所生殖生物学开放研究实验室

当前国际上在生殖生物学研究方面进展迅速。主要有下列若干方面:在激素调控和作用机理方面主要有 C—AMP 和 Ca 离子的调节机理;激素受体的分析和激素受体复合物的转运、储存、降解以及对基因表达调节的原理;激素的反向调节和激素内入的机制,生殖神经内分泌学研究等,在着床机理方面,近年已进入细胞和分子水平。集中探讨着床信息的活性物质。包括子宫和胚泡中肽类物质的分离与纯化,信使的物质基础,胚泡与子宫的功能分     

昆虫生殖与激素的关系

昆虫生殖一般是通过两性来完成的。在生殖过程中,从精子、卵子发生、交配到产卵,除了受外界环境因素(光、温度、湿度、食物等)影响以外;还受内分泌器官的激素来调节控制。昆虫怎样通过外界环境因素诱导内分泌器官的激素来调节控制自身的生殖,这是昆虫生殖生理的一个重要问题。对这个问题的了解不仅在昆虫生殖方面有理论意义,而且在指导如何抑制害虫生殖和大量繁育益虫具有实际意义。     

蜕皮激素对昆虫生长及生殖过程的调控

蜕皮激素、保幼激素及神经激素在调节昆虫生长及生殖方面起到重要的作用。本文从蜕皮激素的合成过程、其活性形式20羟基蜕皮酮的作用模式、蜕皮激素与保幼激素的相互调节机制这三个方面综述了蜕皮激素在昆虫生长及生殖过程中的调控作用。     

蛙类促性腺激素释放激素的研究

蛙类促性腺激素释放激素的研究李远友林浩然（中山大学生物系广州５１０２７５）关键词促性腺激素释放激素特性作用蛙促性腺激素释放激素（ＧｎＲＨ）是脊椎动物脑垂体促性激素（ＧｔＨ）合成和释放的主要调节者,在生殖功能神经激素调控中起关键作用。近年来,哺乳类和...     

硬骨鱼类促性腺激素的种类,结构功能及分泌调节的研究进展

促性腺激素（Ｇｏｎａｄｏｔｒｏｐｉｎ,ＧｔＨ）是硬骨鱼类脑垂体分泌的在其生殖周期调节中起中心作用的激素。有关ＧｔＨ种类,结构功能及分泌调节的研究较多,特别是近十年来,随着分子生物学的发展和新的生化技术的应用,这方面研究进展很快,本文综述这方面的进展。...     

Ghrelin与生殖

ghrelin是1999年发现的一个含有28个氨基酸残基的多肽,为生长激素促分泌素受体(GHS-R)的内源性配体。具有调节能量平衡等多种生物学功能。近年来许多研究表明ghrelin对生殖激素、性腺、胎儿的发育、妊娠和泌乳均有一定的影响,并且,ghrelin及其受体广泛存在于生殖轴中。提示ghrelin对生殖系统具有重要的调节作用。     

CRH suppressed TGFβ1-induced Epithelial–Mesenchymal Transition via induction of E-cadherin in breast cancer cells

Since its discovery in biopsies from breast cancer patients, the effect of corticotropin-releasing hormone (CRH) on carcinoma progression is still unclear. Transforming growth factorβ1 (TGFβ1) promotes Epithelial–Mesenchymal Transition (EMT) and induces Snail1 and Twist1 expressions. Loss of epithelial cadherin (E-cadherin) mainly repressed by Snail1 and Twist1, has been considered as hallmark of Epithelial–Mesenchymal Transition (EMT). Two breast cancer cell lines, MCF-7 and MDA-MB-231 were used to investigate the effect of CRH on TGFβ1-induced EMT by transwell chamber. And HEK293 cells were transiently transfected with CRHR1 or CRHR2 to explore the definite effects of CRH receptor. We reported that CRH inhibited migration of human breast cancer cells through downregulation of Snail1 and Twist1, and subsequent upregulation of E-cadherin. CRH inhibited TGFβ1-mediated migration of MCF-7 via both CRHR1 and CRHR2 while this inhibition in MDA-MB-231 was mainly via CRHR2. Ectopic re-expression of CRHR1 or CRHR2 respectively in HEK293 cells increased E-cadherin expression after CRH stimulation. Furthermore, CRH repressed expression of mesenchymal marker, N-cadherin and induced expression of Occludin, inhibiting EMT in MCF-7 & MDA-MB-231. Our results suggest that CRH may function as a tumor suppressor, at least partly by regulating TGFβ1-mediated EMT. These results may contribute to uncovering the effect of CRH in breast tumorigenesis and progression.     

Differential regulation of MAP kinase activity by corticotropin-releasing hormone in normal and neoplastic corticotropes

Corticotropin-releasing hormone (CRH) plays an important role in regulating the development and function of hypothalamic-pituitary-adrenal axis. The mechanisms by which CRH regulates tissue-specific growth, differentiation and gene expression remain to be established. In the present study, we show that CRH differentially regulates MAP kinase activity in normal ovine anterior pituitary cells and mouse corticotrope AtT20 cells. Incubation of ovine normal anterior pituitary cells with CRH increased MAP kinase activity, an effect mimicked by cAMP and inhibited by the protein kinase A inhibitor H89. In contrast, incubation of mouse pituitary tumor AtT20 cells with CRH inhibited MAP kinase activity, an effect also mimicked by forskolin and inhibited by H89. This decrease in MAP kinase activity occurred with a time course similar to the increase seen in normal anterior pituitary cells. Furthermore, both effects of CRH on MAP kinase activity were inhibited by atrial natriuretic peptide (ANP). ANP also reversed the inhibition of DNA synthesis induced by CRH in AtT20 cells. Thus, CRH may differentially regulate cell growth in sheep normal anterior pituitary and mouse tumor corticotropes by modulating MAP kinase activity through a mechanism dependent on cAMP production and subject to regulation by ANP.     

Ethnic differences in adrenocorticotropic hormone, cortisol and corticotropin-releasing hormone during pregnancy

Significant ethnic disparities exist in reproductive outcomes. A potential contributing factor may be the functioning of the hypothalamic-pituitary-adrenal (HPA) axis and placenta during pregnancy. In the present study, levels of cortisol, ACTH and CRH were determined longitudinally from the plasma of 310 African American, Hispanic and non-Hispanic White women at 18-20, 24-26 and 30-32 weeks' gestation. During pregnancy, African American women exhibited lower levels of cortisol than non-Hispanic women and higher levels of ACTH than Hispanic women. The trajectory of CRH increase also differed by ethnicity, with African Americans exhibiting the lowest levels both early and late in pregnancy. Higher levels of cortisol at 18-20 weeks were associated with higher levels of CRH at 30-32 weeks among the African American and Hispanic women, but not among non-Hispanic women. Ethnic differences persisted when adjusting statistically for sociodemographic and biomedical factors. The findings are consistent with the possibility that ethnic disparities in adverse birth outcomes may be due, in part, to differences in HPA axis and placental function.     

Cerebrospinal fluid and plasma corticotropin-releasing hormone in senile dementia.

Cerebrospinal fluid (CSF) levels of corticotropin-releasing hormone (CRH) and ACTH, and plasma levels of CRH, ACTH and cortisol were determined in samples taken simultaneously from 28 patients with dementia including senile dementia of the Alzheimer type (SDAT), multi-infarct dementia (MID), dementia following a cerebrovascular accident (CVD), and the borderline-to-normal state. CRH levels in CSF were significantly reduced in patients with SDAT and CVD, but not in those with MID, as compared with the borderline cases. ACTH levels in CSF were significantly reduced in the patients with SDAT compared to those with MID. Reduced CRH levels in CSF were found in the patients who showed severe dementia and poor activities of daily living (ADL). Plasma levels of CRH, ACTH and cortisol were normal and were not significantly different among the four groups of patients. CRH levels in CSF were positively correlated with ACTH levels in CSF, but not with the levels of plasma CRH, ACTH or cortisol. Plasma CRH levels were positively correlated with plasma ACTH levels. These results suggest that: 1) abnormalities in the extrahypothalamic CRH system play a role in the pathophysiology of senile dementia, which may not be specific to SDAT; 2) CSF CRH is correlated with the severity of dementia and ADL; 3) the levels of CRH in CSF and plasma are independent, and 4) the plasma CRH reflects, at least in part, the activity of the hypothalamic CRH regulating the secretion of pituitary ACTH.     

Galectin-1 Overexpression in Endometriosis and Its Regulation by Neuropeptides (CRH,UCN) Indicating Its Important Role in Reproduction and Inflammation

Endometriosis is an inflammatory disease of women of reproductive age featured by the presence of ectopic endometrium and is strongly related to infertility. Galectins, carbonhydrate-binding proteins, have been found to have pro- or anti-inflammatory roles in the reproductive tract and in pathological conditions concerning infertility. Galectin-1, which is expressed at endometrium and decidua, plays a major role in implantation and trophoblast invasion. Also, the neuropeptides, corticotropin releasing hormone (CRH) and urocortin (UCN) and their receptors are expressed in eutopic and ectopic endometrium showing a differential expression pattern in endometriotic women compared to healthy ones. The aim of this study was to examine the galectin-1 expression in endometriotic lesions and compare its expression in eutopic endometrium of endometriotic and healthy women. Furthermore, we examined the effect of CRH and UCN in galectin-1 expression in Ishikawa cell line and macrophages and investigated the implication of CRHR1 in these responses. Eutopic and ectopic endometrium specimens, Ishikawa cell line and mice macrophages were used. Immunohistochemistry and western blot analysis were performed in order to identify galectin-1 expression in ectopic and eutopic endometrium of women with and without endometriosis and the regulatory effect of CRH and UCN on galectin-1 expression. This study presents for the first time that galectin-1 is overexpressed in endometriotic lesions compared to eutopic endometrium of endometriotic women and is more abundantly expressed in eutopic endometrium of disease women compared to healthy ones. Furthermore, it is shown that CRH and UCN upregulate galectin-1 expression in Ishikawa cell line and macrophages and this effect is mediated through CRHR1. These results suggest that galectin-1 might play an important role in endometriosis pathology and infertility profile of women suffering from endometriosis by being at the same time regulated by CRH and UCN interfering in the immune disequilibrium which characterizes this pathological condition.     

Evidence suggesting that ghrelin O-acyl transferase inhibitor acts at the hypothalamus to inhibit hypothalamo-pituitary-adrenocortical axis function in the rat

Production of n-octanoyl-modified ghrelin (GHREL), an active form of the peptide requires prohormone processing protease and GHREL O-acyltransferase (GOAT), as well as n-octanoic acid. Recently a selective GOAT antagonist (GO-CoA-Tat) was invented and this tool was used to study the possible role of endogenous GHREL in regulating HPA axis function in the rat. Administration of GOAT inhibitor (GOATi) resulted in a notable decrease in plasma ACTH, aldosterone and corticosterone concentrations at min 60 of experiment. Octanoic acid (OA) administration had no effect on levels of studied hormones. Plasma levels of unacylated and acylated GHREL remained unchanged for 60min after either GOATi or OA administration. Under experimental conditions applied, no significant changes were observed in the levels of GOAT mRNA in hypothalamus, pituitary, adrenal and stomach fundus. After GOATi injection hypothalamic CRH mRNA levels were elevated at 30 min and pituitary POMC mRNA levels at 60 min. Both GOATi and OA lowered basal, but not K(+)-stimulated CRH release by hypothalamic explants and had no effect on basal or CRH-stimulated ACTH release by pituitary slices. Neither GOATi nor OA affected corticosterone secretion by freshly isolated or cultured rat adrenocortical cells. Thus, results of our study suggest that in the rat endogenous GHREL exerts tonic stimulating effect on hypothalamic CRH release. This effect could be demonstrated by administering rats with selected inhibitor of ghrelin O-acyltransferase, the enzyme responsible for GHREL acylation, a process which is absolutely required for both GHSR-1a binding and its central endocrine activities.     

Differential Expression of CRH,UCN, CRHR1 and CRHR2 in Eutopic and Ectopic Endometrium of Women with Endometriosis

Endometriosis is considered as a benign aseptic inflammatory disease, characterised by the presence of ectopic endometrium-like tissue. Its symptoms (mostly pain and infertility) are reported as constant stressors. Corticotropin releasing hormone (CRH) and urocortin (UCN) are neuropeptides, strongly related to stress and inflammation. The effects of CRH and UCN are mediated through CRHR1 and CRHR2 receptors which are implicated in several reproductive functions acting as inflammatory components. However, the involvement of these molecules to endometriosis remains unknown. The aim of this study was to examine the expression of CRHR1 and CRHR2 in endometriotic sites and to compare the expression of CRHR1 and CRHR2 in eutopic endometrium of endometriotic women to that of healthy women. We further compared the expression of CRH, UCN, CRHR1 and CRHR2 in ectopic endometrium to that in eutopic endometrium of women with endometriosis. Endometrial biopsy specimens were taken from healthy women (10 patients) and endometrial and endometriotic biopsy specimens were taken from women with endometriosis (16 patients). Τhe expression of CRH, UCN, CRHR1, and CRHR2 was tested via RT-PCR, immunohistochemistry and Western blotting. This study shows for the first time that CRH and UCN receptor subtypes CRHR1β and CRHR2α are expressed in endometriotic sites and that they are more strongly expressed (p<0.01) in eutopic endometrium of women with endometriosis compared to healthy women endometrium at the mRNA and protein level. CRH, UCN, CRHR1 and CRHR2 mRNA were also more highly expressed in ectopic rather than eutopic endometrium (CRH, UCN, CRHR2α: p<0.01, CRHR1β: p<0.05) and protein (CRH and UCN: p<0.05, CRHR1 and CRHR2: p<0.01) in women with endometriosis. These data indicate that CRH and UCN might play an immunoregulatory role in endometriotic sites by affecting reproductive functions such as decidualization and implantation of women with endometriosis.     

Regulation of corticotropin-releasing hormone in vitro

Studies examining regulation of corticotropin-releasing hormone (CRH) in vitro have been used to validate findings obtained in vivo and more importantly have been used as model systems to better understand signalling mechanisms responsible for the expression of the CRH gene and peptide. Most in vitro studies examining CRH have utilized hypothalamic tissue while a few have focused on the amygdala. Furthermore, clonal cell lines have also been utilized as models of central nervous system CRH neurons. Stimuli that have been implicated in regulating hypothalamic CRH in vitro include protein kinase A (PKA) and protein kinase C (PKC) activators, glucocorticoids, biogenic amines, cytokines and the gaseous neurotransmitters. CRH levels in the amygdala in vitro are affected by some of the same stimuli that regulate hypothalamic CRH; however there is evidence supporting differential regulation of CRH in these two brain regions by some of the same stimuli. Only a few studies in aggregate have investigated the signal transduction mechanisms responsible for CRH expression. These mechanistic studies have focused on PKA- and glucocorticoid-mediated changes in CRH expression. Clearly much more investigative work in better understanding CRH regulation in vitro is needed.     

In vitro regulation of corticotropin-releasing hormone

Studies involving regulation of corticotropin-releasing hormone (CRH) in vitro have been used to validate findings obtained in vivo and more importantly have been used as model systems to better understand signalling mechanisms responsible for the expression of the CRH gene and peptide. Many in vitro studies examining CRH have utilized hypothalamic tissue while a few have focused on the amygdala. Clonal cell lines have also been utilized as models of central nervous system CRH neurons. Stimuli that have been implicated in regulating hypothalamic CRH regulation in vitro include protein kinase A (PKA) and protein kinase C (PKC) activators, glucocorticoids, biogenic amines, cytokines and the gaseous neurotransmitters. Amygdalar CRH levels in vitro are affected by some of the same stimuli that regulate hypothalamic CRH; however there is evidence supporting differential regulation of CRH in these two brain regions by some of the same stimuli. Only a few studies in aggregate have investigated signal transduction mechanisms and these studies have focused on PKA- and glucocorticoid-mediated changes in CRH expression. Thus, much more investigative work in better understanding CRH regulation in vitro is needed.