Changing effects of estrogen and progesterone on the hypothalamo-hypophyseal in rats from birth to sexual maturity

Tritium labeled steroids were administered to female rats to detemine the hormonal effect upon the hypothalomo-hypophyseal system during the period from infancy to sexual maturity. Stintograms of collected fluids showed a coincidence between the onset of selective tritiated-estrogen uptake by the anterior hypothalamus and the eminenta mediana and the onset of positive feedback action of the estrogen. The hypophysis showed a simultareous selective accumulation of tritiated-estrogen during the study. In the critical period of hypothalamic neuronal competition, autoradiographic examination showed a high concentration of tritiated-estrogen in the preptic-supra-chiasmatic area, but not in the anterior hypothalamus. There was a selective concentration of tritiated-estrogen in the posterior hypothalamus of the mature female rats and in the hypophysis throughout the study. The protective effects of progesterone and its positive action at the onset of luteinizing hormone release by estrogens could not be determined.     

The role of leptin in fertility

The relationship between metabolism and reproduction remains a mystery in female endocrinology. Such substances as insulin, amino acids and IGFBP-I have been proposed as signals of body mass fat on the genital axis. Today this role is claimed by leptin, a protein hormone decoded from the obesity gene and is secreted exclusively from adipose tissue. This hormone acts on the central nervous system (CNS) to result in the suppression of food intake and increase in energy consumption. What is more, it also influences the capacity for reproduction. This paper reports findings with regard to the factors influencing the secretion of leptin and identification of the leptin's hormonal receptors. Particular emphasis was placed on the relationship between secretion of leptin and disturbances in menstruation, the anticipated role of this hormone in the pathogenesis of the polycystic ovarian syndrome (PCOS) and its effects on the reproductive capacity.     

The effect of diabetes on alpha2-adrenergic receptor activity in the reproductive centers of the female rat brain

OBJECTIVE: We hypothesized that known diabetes-induced deficits in female rat reproduction may result in part from decreased central alpha(2)-noradrenergic receptor density or affinity.Study Design: Female rats were oophorectomized and divided into 2 groups; one group received streptozocin during the operation to induce diabetes, and the other served as a nondiabetic control group. Random blood glucose levels were measured. Half the rats in each group were killed on postoperative day 10, and half were killed on postoperative day 14. Direct radioligand binding assays were performed on tissue prepared from the hypothalamus, preoptic area, and cortex of each rat. Analysis of variance was used to evaluate intergroup differences in receptor concentration or equilibrium constant. RESULTS: We detected no significant difference in the mean receptor concentration or equilibrium constant between the groups with and without diabetes in the hypothalamus, the preoptic area, and the cortex on postoperative day 10 or 14. CONCLUSION: Diabetes-induced impairments in female rat reproduction do not involve alterations in alpha(2)-receptor density or affinity in the hypothalamus, preoptic area, or cortex.     

Estrogen and folliculogenesis: is one necessary for the other?

PURPOSE OF REVIEW: During folliculogenesis the primordial follicle undergoes several steps of maturation in order to develop into a preovulatory follicle. The exact role of estrogen during this process has not yet been fully assessed. RECENT FINDINGS: Estrogen appears to regulate cyclic gonadotropin release via its action on estrogen receptor alpha in the hypothalamus/hypophysis axis and to enhance folliculogenesis through its actions via estrogen receptor beta in the ovary. In addition, a role of estrogen during the very early stages of folliculogenesis is possible. However, it is likely that oocyte quality and developmental potential are not estrogen dependent. This might explain the lack of association between estrogen and in-vitro fertilization outcome in humans. SUMMARY: The advent of knockout mice models has enhanced our understanding of the role of estrogen during folliculogenesis. Existing data suggest that estrogen might be involved in the very early steps of this process, but its role in sustaining ovulation is mainly central.     

闭经性疾病的性激素特点和鉴别诊断

闭经性疾病根据发病原因不同可分为：下生殖道异常、子宫疾病、卵巢功能异常、垂体功能异常和中枢下丘脑功能异常。通过检测雌激素、孕激素、促卵泡生成素和雄激素等性激素水平,根据其不同的特点,可以有助于鉴别诊断闭经性疾病。     

侧脑室注射促黄体素释放激素类似物对大鼠妊娠的影响

本文报道了侧脑室注射LHRH类似物(100微克/只)对大鼠胚泡着床、早孕的影响,以及侧脑室注射~(125)I-LHRH 在大鼠体内的分布。结果表明,于大鼠着床前或着床期侧脑室注射LHRH 类似物具有明显的抗着床作用,但于着床后给药无抗早孕作用;~(125)I-LHRH 的放射活性特异地集中于下丘脑和垂体,提示侧脑室注射LHRH 类似物的抗着床作用可能主要是通过下丘脑和垂体而实现的。     

闭经性疾病的性激素特点和鉴别诊断

闭经性疾病根据发病原因不同可分为：下生殖道异常、子宫疾病、卵巢功能异常、垂体功能异常和中枢下丘脑功能异常。通过检测雌激素、孕激素、促卵泡生成素和雄激素等性激素水平,根据其不同的特点,可以有助于鉴别诊断闭经性疾病。     

Products toxic to reproduction used in the occupational environment: Definition, risk assessment, classification

European regulations (transcribed into French law) aimed at protecting employees from chemicals toxic to reproduction enable classification and labelling of such substances, if they are liable to cause an alteration of male or female reproductive functions or capacity, or to induce non-hereditary harmful effects on their offspring. Three categories can be used to classify these substances in two areas, namely their impairment of fertility and their effects on development. This classification is rarely based on epidemiological study results, but most often on those of experimental toxicological studies conducted by substance manufacturers. These reproduction toxicological studies are only compulsory above a certain tonnage placed on the market. The high level of this tonnage means that these tests are effectively only conducted on rare occasions. It is reckoned that there is no reproduction experimental data for over 95% of substances newly placed on the market. These products therefore appear to be reproduction non-toxic only because they have not been tested. This is a major fault in the current labelling system, which does not allow non-toxic products to be differentiated from non-tested products. The future EU regulatory framework for Registration, Evaluation and Authorisation of CHemicals (REACH) will only slightly enhance information in this area. It can be estimated that over 80% of chemical products will not be exhaustively tested for reproduction and nearly 75% will not be tested to any degree.     

Leptin and reproduction

In the few years since leptin was identified as a satiety factor in rodents, it has been implicated in the regulation of various physiological processes. Leptin has been shown to promote sexual maturation in rodent species and a role in reproduction has been investigated at various sites within the hypothalamo-pituitary-gonadal axis. This review considers the evidence that leptin (or alteration in amount of body fat) can affect reproduction. There is evidence that leptin plays a permissive role in the onset of puberty, probably through action on the hypothalamus, where leptin receptors are found in cells that express appetite-regulating peptides. There is little evidence that leptin has a positive effect on the pituitary gonadotrophs and the gonads. There is also very little indication that leptin acts in an acute manner to regulate reproduction in the short term. It seems more likely that leptin is a 'barometer' of body condition that sends signals to the brain. Studies in vitro have shown negative effects on ovarian steroid production and there are no reports of effects on testicular function. Leptin concentrations in plasma increase in women during pregnancy, owing to production by the placenta but the functional significance of this is unknown. A number of factors that affect the production and action of leptin have yet to be studied in detail.     

促性腺激素释放激素及其受体研究进展

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。其通过下丘脑-垂体-性腺轴调节女性发育和生殖功能,同时还以自分泌和旁分泌的方式作用于垂体外组织。研究发现,GnRH及其受体均存在多种亚型,并在正常及异常生殖相关组织,包括子宫内膜异位症、子宫内膜癌和卵巢癌等表达。了解GnRH不同亚型的作用机制进而开发其类似物,以达到治疗子宫内膜异位症、不孕和肿瘤等妇科疾病的目的,是国外最新研究的热点之一。     

Menstrual cycle, opioids and hypothalamic amenorrhea: from physiology to pathology

The central part of menstrual cyclicity is the arcuate nucleus within the mediobasal hypothalamus, which is shown to be the origin of GnRH. This neuronal oscillator is influenced by many endogenous substances and its periodically activity is modulated by them. The endogenous opioids are such substances. They are widely distributed within the organism and are endogenous ligands of opiate receptors. The endogenous opioids participate in many somatic functions such as regulation of ovarian cyclicity. Furthermore they are causal involved in hypothalamic amenorrhea.     

Effects of the posterior hypophysis and ovary on pheromonal production in normal females and in the reproductive behavior of male rats treated with D,L-propranolol

Posterior hypophysis homogenates of female rats stimulated with epinephrine subcutaneously contain a pheromonal factor that increments significantly the incidence of fertile coitus after having been placed in the oronasal groove of rats in proestro (69.2% fertile coitus vs. 36.6% of control). These same homogenates obtained from spayed rats increment reproductive activity even more (80.0% fertile coitus). The homogenates do not act by an intraperitoneal route. Male rats under the effect of high doses of D,L-propranolol reduce reproductive activity (21.2% fertile coitus). This effect is counteracted by posterior hypophysis homogenates from female rats stimulated with epinephrine, placed in the oronasal groove (72.2% fertile coitus). The homogenates of anterior hypophysis do not increase the reproductive capacity of rats in proestro, and do not modify the propranolol effects in male rats.     

促性腺激素释放激素及其受体研究进展

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。其通过下丘脑-垂体-性腺轴调节女性发育和生殖功能,同时还以自分泌和旁分泌的方式作用于垂体外组织。研究发现,GnRH及其受体均存在多种亚型,并在正常及异常生殖相关组织,包括子宫内膜异位症、子宫内膜癌和卵巢癌等表达。了解GnRH不同亚型的作用机制进而开发其类似物,以达到治疗子宫内膜异位症、不孕和肿瘤等妇科疾病的目的,是国外最新研究的热点之一。     

Disposition of pesticides and toxicants in the human reproductive system in cases of acute poisoning

The aim of this study was to estimate the penetration of some of the pesticides and toxicant substances in the human reproductive system. This knowledge is valuable because of the possible adverse influence of these substances on the human reproduction system and the development of the foetus during pregnancy. The existing data is mainly concerned with the results of experimental studies on animals or epidemiological studies. Here we report data concerning the disposition of several toxic xenobiotics (pesticides and solvents) in the tissues of the human reproductive system as well as in other organs and glands. Data was collected from cases of acute poisonings and derived mostly from autopsy materials. Xenobiotics were found to penetrate sampled tissues such as the testes, ovaries, epididymis, uterus, thyroid gland, as well as other human tissues. Further studies will clarify and confirm peculiarities of the penetration of a wide range of substances in various body tissues and will be the base of the estimation of the role of these toxicants in human reproductive ability and the outcome of pregnancy in humans.     

Reproductive ageing and conflicting clocks: King Midas’ touch

The population attempting pregnancy and having babies is ageing. Gynaecological and obstetric complications worsen with age. Maternity services are struggling. Increasing rates of infertility and complications are not matched by the marvels in the laboratory. This paper argues that assisted reproduction treatment has had a damaging social impact. Despite its public acclaim, it helps few and fails many more. The assisted reproduction industry could take a new and revolutionary direction towards empowering men to experience pregnancy, producing babies from artificial gametes, with a final goal being the liberation of both women and men from the burdens and dangers of pregnancy through the development of artificial wombs.This paper seeks to give a brief explanation as to why women are having children older and discusses how reproduction technologies have contributed to this trend. It argues that reproduction technologies is not a panacea for this problem and has in fact contributed to it. We suggest that as a means of promoting reproduction equality between the sexes, science needs to extend the reproduction experience to men, as well as developing artificial gametes and wombs.VIDEO LINK: http://sms.cam.ac.uk/media/1401028     

Beyond the yellow wallpaper

This paper, firstpresented ata conference in 1983, challenges the myth thathealth is a medical product and that the inequalities between men and women are easilyremoved. It analyses the differences between health, health care and medical care in the context of'women and health, and of women as providers as well as users of these. Using the lessons of a short story by Charlotte Perkins Gilman called 'The Yellow Wallpaper, the paper identifies and discusses the three most important unsolved problems of women and health as: production, reproduction and the medicalisation of the psychological costs of women's situation in the form of mental illness. Next, it calls for recognition of health as a social product and for women to tell the truth about our own experiences, because these determine women's health. Lastly, the paper shows how women's health-giving role in reproduction and in ensuring family welfare holds the causes of women's ill-health within it and calls for a world in which women who ask for change are taken seriously.     

Neuroendocrine control of reproduction and its therapeutic manipulation with GnRH and its analogs

The hypothalamus mediates the neuroendocrine control of reproduction in both males and females through pulsatile secretion of GnRH. The anterior pituitary gland, in turn, appears to require this episodic GnRH stimulation in order to secrete the gonadotropins LH and FSH in a physiologic fashion. Deficiency of GnRH manifests as a failure to attain puberty in both sexes, and in females it may also produce amenorrhea and/or anovulation. Replacement regimens of GnRH which employ an episodic pattern of delivery correct the deficiency of endogenous GnRH secretion and stimulate gonadotropin secretion, gonadal steroidogenesis and gametogenesis. However, continuous occupancy of the GnRH receptor by native GnRH and/or its long-acting analogs paradoxically inhibits pituitary gonadotropin secretion. GnRH analogs have been synthesized which exhibit greater affinity and prolonged occupancy on the GnRH receptor and can produce pituitary desensitization of gonadotropin secretion. Chronic administration of these GnRH analogs is capable of producting a selective "medical castration." Thus, by altering the frequency of episodic GnRH administration or by utilizing long-acting GnRH analogs it is possible to stimulate or suppress the neuroendocrine control of reproduction. The use of GnRH or its long-acting analogs has demonstrated a profound clinical impact in restoring or inhibiting fertility.     

Prospective function of placental leptin at maternal-fetal interface

Leptin is an endocrine and a growth factor which is important for regulation of body fat, feeding, and energy homeostasis. The anti-obesity function of leptin has been recently extended to reproduction, puberty and pregnancy as an endocrine signal to the hypothalamus. Leptin controls the functional integrity of the feto-placental unit thereby maintaining pregnancy by virtue of its immunomodulatory property via T lymphocytes or other proto-oncogenes. Dysregulation of autocrine/paracrine function of leptin at feto-placento-maternal interface may be implicated in the pathogenesis of recurrent miscarriage gestational diabetes, pre-eclampsia and intra-uterine fetal growth retardation including disturbance of fetal bone turnover. This review will focus on the role of leptin in normal and abnormal pregnancy and fetal growth.     

Appetite control and reproduction: leptin and beyond

It is now recognized that appropriate regulation of reproduction, energy intake, and energy expenditure, and thus maintenance of body weight and fertility, relies on complex hypothalamic neurocircuitry. Feeding and reproductive function are closely linked. During times of undernourishment and falling body fat the reproductive axis is down-regulated. Circulating factors and hypothalamic circuits coordinate these responses. Leptin has been described to be an important peripheral signal that indicates body fat stores to the hypothalamus and thus links nutrition and reproduction. Leptin acts by altering neuropeptide circuits in the hypothalamus, which alter gonadotropin-releasing hormone release and food intake. The importance of key neuropeptide systems identified in rodents is now being established in man. Notably mutations in the melanocortin MC4 receptor are found in up to 4% of the morbidly obese, and in a proportion of patients with anorexia nervosa mutations have been identified in the agouti-related peptide gene (AgRP), which codes for an endogenous antagonist of this receptor. Intranasal administration of a melanocortin fragment known to activate the MC4 receptor decreases adiposity in humans. The melanocortin system has been shown to influence the reproductive axis in rodents. However, the role of the melanocortin system in the control of reproduction in humans remains to be established. Since the discovery of leptin, attention has also been focused on peripheral signals that regulate reproduction, food intake, and energy expenditure, either directly or via feedback on hypothalamic circuits. Notable new discoveries in this area include the gastric hormone ghrelin. Circulating ghrelin stimulates food intake in rodents and humans, although an influence on the reproductive axis is yet to be reported.     

Effects of stress on reproduction in non-rodent mammals: the role of glucocorticoids and sex differences

The means by which stress influences reproduction is not clearly understood, but may involve a number of endocrine, paracrine and neural systems. Stress impacts on the reproductive axis at the hypothalamus (to affect GnRH secretion) and the pituitary gland (to affect gonadotrophin secretion), with direct effects on the gonads being of less importance. Different stressors have different effects and there are differences in response to short- and long-term stress. Many short-term stresses fail to affect reproduction and there are reports of stimulatory effects of some 'stressors'. There are species differences in the way that specific stressors affect reproduction. Sex differences in the effects of a particular stressor have been delineated and these may relate to effects of stress at different levels of the hypothalamo-pituitary axis. The significance of stress-induced secretion of cortisol varies with species. In some instances, there appears to be little impact of short-term increases in cortisol concentrations and protracted increases in plasma concentration seem to be required before any deleterious effect on reproduction is apparent. Issues of sex, sex steroid status, type of stressor and duration of stress need to be considered to improve understanding of this issue.