女性生殖内分泌与全身内分泌疾病

现代内分泌系统的概念已涉及几乎全身组织或细胞。下丘脑促性腺激素释放激素(GnRH)-促性腺激素(Gn)脉冲分泌激活是启动卵巢轴功能的关键。其与4个下丘脑内分泌系统存在复杂的联系。神经内分泌免疫网络、神经内分泌营养调节网络也影响GnRH-Gn脉冲分泌或卵巢配子生成及性激素合成。介绍全身主要内分泌疾病对女性生殖的影响,并通过介绍一个心理神经内分泌失调疾病——功能性下丘脑性无排卵(functional hypothalamic anovulation,FHA),阐述应激对全身及女性生殖的影响。     

生殖轴内分泌网络的因子分析模型

生殖轴内分泌活动是重要的生理功能。现代医学认为，神经内分泌系统与免疫系统之间有着广泛而密切的联系，并有许多研究表明下丘脑是神经内分泌免疫功能联接的调控枢纽，在生殖神经内分泌免疫关系中。下丘脑的GnRH（gonadotropin releasing hormone。促性腺激素释放激素）是调节下丘脑-垂体-卵巢轴、调节生殖内分泌的关键因子，GnRH作用到脑垂体上，影响脑垂体FSH（follicle stimulating hormone，卵泡刺激素）和LH（lutuneizing hormone。黄体生成素）的合成与分泌，进而调控卵巢E2（雌激素）和P（孕激素）的分泌。下丘脑β-EP（β-Endorphin，β-内啡肽）参与调节GnRH的分泌，如心理应激情况时，下丘脑β-EP增高能抑制GnRH分泌，使下丘脑-垂体-卵巢轴紊乱，导致卵巢内分泌失调。     

性激素六项检测,你看懂了吗

女性生殖内分泌系统激素包括下丘脑、垂体、卵巢分泌的激素。各器官分泌的各类激素相互调节、相互影响,从而发挥正常的生理功能。如下丘脑分泌的促性腺激素释放激素通过调节垂体促性腺激素的分泌调控卵巢功能,卵巢分泌的性激素又对下丘脑-垂体系统有反馈调节的作用。     

多囊卵巢综合征与神经内分泌功能异常

多囊卵巢综合征是育龄妇女最常见的妇科内分泌疾病之一,是引起无排卵性不孕的主要原因,其内分泌异常表现为黄体生成素(促性腺激素释放激素)脉冲波持续快速升高,黄体生成素/重组绒促卵泡激素的比例失调,重组绒促卵泡激素水平下降,卵泡形成受损及高雄激素产生.通过增强下丘脑对黄体酮的敏感性,可以抑制黄体生成素持续快速升高,体内过多的雄激素分泌却减弱了下丘脑对黄体酮的敏感性,进而削弱了黄体酮对促性腺激素释放激素的减速调节,加速黄体生成素(促性腺激素释放激素)脉冲波持续升高.促性腺素分泌的异常、高雄激素的产生和卵巢功能障碍都可能是多囊卵巢综合征内分泌功能异常的重要原因.     

多囊卵巢综合征神经内分泌病因机制的研究进展

多囊卵巢综合征(PCOS)是女性常见的生殖内分泌疾病,PCOS的典型特征是高雄激素血症、排卵障碍和卵巢多囊样改变.高雄激素血症通常是由垂体黄体生成激素(LH)脉冲分泌增加所致.多数PCOS女性表现为血清LH水平升高,LH脉动分泌频率升高.LH脉动分泌频率异常升高反映了促性腺激素释放激素(GnRH)神经回路异常活跃,提示...     

浅谈黄体酮

正女性内分泌激素包括下丘脑-垂体-卵巢轴系腺体分泌的激素,这些激素通过复杂的刺激和抑制信号协调女性的月经、生育以及全身的健康。下丘脑向垂体门脉系统脉冲式分泌促性腺激素释放激素,刺激垂体前叶合成和释放促卵泡激素和黄体生成素,卵巢在其作用下产生卵泡的发育、成熟和排卵。排卵后卵巢的黄体分泌黄体酮,即孕酮。孕酮作用于体温中枢,可使体温上     

饮食和营养与生殖轴系

钦食和营养通过神经内分泌通路从下丘脑-垂体-性腺轴系的3个水平上影响生殖,最终的作用通路是影响促性腺激素释放激素(GnRH)脉冲产生 糖被认为是营养与生殖之间连接的代谢要素;而瘦素将体内脂肪储存的信号传导到中枢,该信号对GnRH分泌也是必须的 影响GnRH脉冲和促性腺激素产生除代谢物质和激素信号外,另一条通路是下丘脑-垂体-肾上腺轴的激活,而且营养不良对性腺本身具有直接的影响     

饮食和营养与生殖轴系

饮食和营养通过神经内分泌通路从下丘脑-垂体-性腺轴系的3个水平上影响生殖,最终的作用通路是影响促性腺激素释放激素(GnRH)脉冲产生.糖被认为是营养与生殖之间连接的代谢要素;而瘦素将体内脂肪储存的信号传导到中枢,该信号对GnRH分泌也是必须的.影响GnRH脉冲和促性腺激素产生除代谢物质和激素信号外,另一条通路是下丘脑-垂体-肾上腺轴的激活,而且营养不良对性腺本身具有直接的影响.     

饮食和营养与生殖轴系

饮食和营养通过神经内分泌通路从下丘脑-垂体—性腺轴系的3个水平上影响生殖，最终的作用通路是影响促性腺激素释放激素(GnRH)脉冲产生。糖被认为是营养与生殖之间连接的代谢要素；而瘦素将体内脂肪储存的信号传导到中枢，该信号对GnRH分泌也是必须的。影响GnRH脉冲和促性腺激素产生除代谢物质和激素信号外，另一条通路是下丘脑-垂体-肾上腺轴的激活，而且营养不良对性腺本身具有直接的影响。     

促性腺激素释放激素类似物在妇科肿瘤治疗中的应用

促性腺激素释放激素（GnRH）是由下丘脑分泌的神经内分泌因子，通过垂体性腺轴控制女性的发育、生殖功能，同时还以自分泌和旁分泌的方式作用于垂体外组织。近年来已在多种肿瘤组织包括子宫肌瘤、子宫内膜癌、卵巢癌、乳腺癌等中发现GnRH及其受体的表达，许多研究证实GnRH类似物可发挥直接或间接的抗肿瘤作用。本文就近年相关的研究进展作一综述。     

Endocrine modifications and interventions during critical illness

The ongoing hypermetabolic response in patients with prolonged critical illness leads to the loss of lean tissue mass. Since the cachexia of prolonged illness is usually associated with low concentrations of anabolic hormones, hormonal intervention has been thought to be beneficial. However, most interventions have been shown to be ineffective and their indiscriminate use even causes harm. Before considering endocrine intervention in these frail patients, a detailed understanding of the neuroendocrinology of the stress response is warranted. It is now clear that the acute phase and the later phase of critical illness behave differently from an endocrinological point of view. The acute stress response consists primarily of an actively-secreting pituitary in the presence of low circulating peripheral anabolic hormones, suggesting resistance of the peripheral tissues to the effects of anterior pituitary hormones. However, when the disease process becomes prolonged, there is a uniformly-reduced pulsatile secretion of anterior pituitary hormones with proportionally reduced concentrations of peripheral anabolic hormones. The origin of this suppressed pituitary secretion is located in the hypothalamus, as hypothalamic secretagogues can reactivate the anterior pituitary and restore pulsatile secretion. The reactivated pituitary secretion is accompanied by an increase in peripheral target hormones, indicating at least partial sensitivity of these tissues to anterior pituitary hormones in this chronic phase of illness. Thus, endocrine intervention with a combination of hypothalamic secretagogues that more completely reactivate the anterior pituitary could be a more physiological and effective strategy for inducing anabolism in patients with prolonged critical illness.     

Lactational control of reproduction

In most mammalian species lactation suppresses fertility. There is no doubt that it is the suckling stimulus that provides the controlling signal, and, in human reproduction, this is the only truly physiological signal that suppresses fertility in normally nourished, healthy women. In breastfeeding women, the return of normal fertility follows a relatively well-defined path progressing through: an almost complete inhibition of gonadotrophin-releasing hormone/luteinizing hormone (GnRH/LH) pulsatile secretion in the early stages of lactation; return of erratic pulsatile secretion with some ovarian follicle development associated with increases in inhibin B and oestradiol; a resumption of apparently normal follicle growth associated with a normal increase in oestradiol, but often an absence of ovulation, or formation of an inadequate corpus luteum; and a return to normal ovulatory menstrual cycles. A key element in controlling the rate of this progression is the impact of the suckling stimulus on the GnRH pulse generator, a common feature of lactation in those species for which there is information. The variability in the duration of lactational amenorrhoea between women is related to the variation in the strength of the suckling stimulus, a unique situation between each mother and baby. Full breastfeeding can provide a reliable contraceptive effect in the first 6 to 9 months, but the precise mechanisms whereby the suckling stimulus affects GnRH pulsatile secretion remain unknown. Many studies on the hypothalamic pathways that might be involved in the translation of the neural suckling stimulus to suppression of hypothalamic GnRH secretion have been undertaken, principally in rats. In women, suckling increases the sensitivity of the hypothalamus to the negative feedback effect of oestradiol on suppressing the GnRH/LH pulse generator, a mechanism that appears to be common across species. In contrast, the role of prolactin in the control of GnRH appears to be species-dependent, with the importance varying from none to an important role in late or throughout lactation. In women, there is little evidence for a role of leptin, opioids or dopamine, although this may merely reflect the ethical dilemma of being able to give sufficient drug to test the system in the mother since these drugs will pass through the breast milk to the baby. Regardless of mechanism, practical guidelines for using breastfeeding as a natural contraceptive have been developed, which allows mothers to utilize the only natural suppressor of fertility in women as an effective means of spacing births.     

Neuroendocrine and reproductive effects of contemporary-use pesticides

Work in our laboratory has focused on the hypothesis that certain environmental contaminants will interfere with reproductive function because they disrupt the neuroendocrine regulation of gonadal function. In this article, we review the evidence that certain classes of contemporary-use pesticides alter gonadotropin secretion through a disruption of hypothalamic mechanisms. Specifically, we discuss the effect of formamidine and dithiocarbamate pesticides on the noradrenergic control of pituitary hormone secretion, ovarian function, and pregnancy in the rat. This is followed by a review of studies evaluating the effect of a chlorotriazine herbicide, atrazine, on the hormonal control of ovulation and lactation. We also discuss the physiological consequences of these endocrine alterations in the female, how toxicant-induced endocrine alterations may differ in physiological outcome in the male and female, and the fact that the reproductive risk assessment of some pesticides that act on the central nervous system (CNS) may be influenced by the development of tolerance.     

A comparison of methods for analyzing time series of pulsatile hormone data

Many endocrine systems are regulated by pulsatile hormones – hormones that are secreted intermittently in boluses rather than continuously over time. To study pulsatile secretion, blood is drawn every few minutes for an extended period. The result is a time series of hormone concentrations for each individual. The goal is to estimate pulsatile hormone secretion features such as frequency, location, duration, and amount of pulsatile and non‐pulsatile secretion and compare these features between groups. Various statistical approaches to analyzing these data have been proposed, but validation has generally focused on one hormone. Thus, we lack a broad understanding of each method's performance. By using simulated data with features seen in reproductive and stress hormones, we investigated the performance of three recently developed statistical approaches for analyzing pulsatile hormone data and compared them to a frequently used deconvolution approach. We found that methods incorporating a changing baseline modeled both constant and changing baseline shapes well; however, the added model flexibility resulted in a slight increase in bias in other model parameters. When pulses were well defined and baseline constant, Bayesian approaches performed similar to the existing deconvolution method. The increase in computation time of Bayesian approaches offered improved estimation and more accurate quantification of estimation variation in situations where pulse locations were not clearly identifiable. Within the class of deconvolution models for fitting pulsatile hormone data, the Bayesian approach with a changing baseline offered adequate results over the widest range of data. Copyright © 2013 John Wiley & Sons, Ltd.     

Hormonelle Folgestörungen bei Adipositas im Kindes- und Jugendalter

There are a number of rare endocrine causes of obesity including defined genetic syndromes. However, there are frequent alterations in endocrine functions in obesity, which are characteristic of the obese state, including disorders of insulin secretion and function, alterations in the function of the growth hormone–IGF-1 axis, the hypothalamic–pituitary–thyroid axis, the hypothalamic–pituitary–adrenal axis, and pubertal development. The characteristic endocrine alterations in obesity may have an influence on energy metabolism and energy storage. Alterations in glucocorticoid production and metabolism and the impaired growth hormone production for example show that these secondary endocrine changes may facilitate further increase in weight. Notwithstanding this, all described endocrine changes are completely or partially reversible under calorie restriction and weight loss.     

闭经的诊断进展

女性正常月经依赖于下丘脑、垂体和卵巢及其激素诱导的子宫内膜之间的相互协调作用,其中任何一个方面出现功能障碍都可能导致闭经,影响生育。引起闭经的病因众多,明确诊断闭经的病因是治疗的关键。病史、体格检查、内分泌功能检查和辅助检查相结合可对闭经进行全面诊断。临床上最常见的闭经病因为下丘脑病变、多囊卵巢综合征、高催乳素血症和卵巢衰竭,综述临床常见闭经病因的诊断进展。     

Ghrelin,an important hormone produced by the stomach

Ghrelin is a hormone produced by endocrine cells in the stomach. Ghrelin stimulates the secretion of growth hormone by the anterior pituitary. This effect is mediated by hypothalamic growth-hormone secretagogue receptors. Binding to these receptors not only stimulates growth hormone secretion, but also has vascular effects (positive inotropic effects), modifies (decreases) insulin sensitivity, affects glucose metabolism (hyperglycaemia) and stimulates gastric-acid production. Antiproliferative effects of ghrelin have been described on experimental tumour models. Ghrelin seems to play a role in stimulating the appetite as well as promoting a more effective storage of food components. Whether or not ghrelin could play any role in the induction of weight gain has yet to be established. This is also true for the role of potential ghrelin antagonists in the induction of weight loss in case of obesity.     

胎盘促肾上腺皮质激素释放激素的作用与调控

胎盘分泌的大量下丘脑内分泌激素促肾上腺素皮质激素释放激素 ,是妊娠期母体血浆促肾上腺素皮质激素释放激素的主要来源。胎盘促肾上腺素皮质激素释放激素可能通过与前列腺素、催产素、皮质激素和雌激素等内分泌激素的相互作用 ,对分娩启动起着重要的作用。妊娠期母体血浆促肾上腺素皮质激素释放激素水平与早产及某些妊娠期疾病关系密切。胎盘促肾上腺素皮质激素释放激素的分泌受促肾上腺素皮质激素释放激素结合蛋白、环磷酸腺苷、糖皮质激素、催产素、孕激素、雌激素、前列腺素、一氧化氮和某些神经递质等多因素的调控。     

Insulin secretion in hypothalamic obesity: diurnal variation and the effect of naloxone

This paper has tested the hypothesis that patients with hypothalamic obesity have altered mechanisms controlling insulin secretion when compared to obese patients without hypothalamic injury. Fasting glucose and insulin values were significantly higher in the morning than in the afternoon in the six control obese patients, but there was no diurnal difference in the six patients with hypothalamic obesity (n=6). The control obese subjects showed a diurnal variation in glucose-stimulated insulin secretion, whereas the patients with hypothalamic obesity did not, suggesting that hypothalamic injury had destroyed diurnal rhythms. Naloxone, an opioid antagonist, acutely suppressed fasting insulin in the six patients with essential obesity but had little effect on fasting insulin in the three patients with hypothalamic obesity or in five normal-weight controls. Naloxone increased insulin sensitivity in the obese control patients, but did not affect either insulin secretion or insulin sensitivity in patients with hypothalamic obesity or in normal weight subjects. Our results support the conclusion that hypothalamic obesity disrupts diurnal rhythms, with the suggestion that opioid peptides affect insulin secretion differently in patients with essential obesity as compared to normal weight subjects or those with hypothalamic obesity.     

Pentachlorophenol exposure in women with gynecological and endocrine dysfunction.

Exposure to wood preservatives containing pentachlorophenol (PCP) was detected in 65 women who consulted the Endocrinological Department of the University Hospital of Obstetrics and Gynecology, Heidelberg, Germany, because of gynecological problems. Blood PCP levels ranged from 20.7 to 133 microg per liter of serum. One hundred and six women with similar clinical conditions, corresponding age and body weight, no PCP exposure in history, and PCP levels below 20 microg per liter of serum served as control group. Significant associations were found between serum PCP concentrations, age, and different parameters of the endocrine system. PCP may act centrally on a hypothalamic or suprahypothalamic level which may result in mild ovarian and adrenal insufficiency. PCP may, therefore, play a role in the increasing infertility problem.