New developments of the effect of melatonin on reproduction

In the past decades, a lot of advances in understanding the biochemistry and physiology of the pineal gland have been made. There is evidence that it interacts with many endocrine as well as non-endocrine tissues to influence their metabolic activity modulating many organs and functions. Melatonin is secreted by the pineal gland in the brain and plays an important role in regulating the neuroendocrine system. This hormone is one of the major role players in the regulation of the circadian sleep-wake cycle. It is normally released from the pineal gland during the night in response to environmental changes in light. Studies have shown that melatonin plays a role in the regulation of many reproductive processes such as puberty, gonadal function, and pregnancy. Beside these, melatonin has been shown to be able to directly neutralize a number of free radicals and reactive oxygen and nitrogen species. The main objective of this review is to provide comprehensive information about the new developments in melatonin research regarding its role in reproduction. A review of international scientific literature was done and a question-and-answer format was used in an attempt to convey comprehensive information in a simple manner. This review discusses evidence currently available relating to the effect of melatonin on reproductive processes. It deliberates the mechanism of action of melatonin, its effect on puberty, testicular and ovafunction, pregnancy, and oxidative stress. A growing body of scientific evidence is suggesting that melatonin plays an important role in reproductive function. It is therefore imperative to highlight the beneficial effects of this hormone in improving the reproductive processes.     

重视卵巢储备功能减退与卵巢早衰对女性健康的影响

卵巢是妇女最重要的生殖器官,卵巢功能包括生殖功能和内分泌功能,其功能的正常发挥对女性生殖健康以及整体健康均意义重大。各种原因导致的卵巢功能过早衰退将不可避免的导致中青年女性提前步入老年期而引发很多问题。卵巢功能减退或卵巢早衰将导致女性生育力下降或丧失、异常子宫出血。卵巢内分泌激素的长期缺乏将给女性带来神经系统、心脑血管系统、皮肤系统、泌尿生殖系统以及骨骼系统等多个系统失调。因此,应重视卵巢储备功能减退及卵巢早衰,及早发现该类患者并给予促进生育及全身健康的治疗。     

Ghrelin: new insights into female reproductive system-associated disorders and pregnancy

Ghrelin is considered the endogenous ligand of growth hormone secretagogue receptor type 1a, and its modulatory actions have been demonstrated in a large array of endocrine and nonendocrine functions. According to recent studies, ghrelin seems to act at different levels of the reproductive system, exerting predominantly inhibitory effects on mammalian reproduction. It has been shown to influence the reproductive system by regulating hormone secretion from the brain and by acting directly on the gonads to affect tissue development and steroidogenesis. Thus, the endocrine network, which integrates energy balance and fertility, might involve ghrelin. Furthermore, ghrelin levels and actions have been assessed in various female reproductive system disorders. The findings could lead to a better understanding of the pathogenesis of these disorders and, possibly, to more beneficial therapeutic strategies.     

Leptin and reproduction: a review

OBJECTIVE: To review recent advances in understanding the role of leptin in the physiology and pathophysiology of reproduction, with a focus on relevant clinical situations. DESIGN: A MEDLINE computer search was performed to identify relevant articles. RESULT(S): Leptin, an adipocyte hormone important in regulating energy homeostasis, interacts with the reproductive axis at multiple sites, with stimulatory effects at the hypothalamus and pituitary and inhibitory actions at the gonads. More recently, leptin has been shown to play a role in other target reproductive organs, such as the endometrium, placenta, and mammary gland, with corresponding influences on important physiologic processes such as menstruation, pregnancy, and lactation. As a marker of whether nutritional stores are adequate, leptin may act in concert with gonadotropins and the growth hormone axis to initiate the complex process of puberty. Conditions in which nutritional status is suboptimal, such as eating disorders, exercise-induced amenorrhea, and functional hypothalamic amenorrhea, are associated with low serum leptin levels; and conditions with excess energy stores or metabolic disturbances, such as obesity and polycystic ovarian syndrome, often have elevated serum or follicular fluid leptin levels, raising the possibility that relative leptin deficiency or resistance may be at least partly responsible for the reproductive abnormalities that occur with these conditions. CONCLUSION(S): Leptin may act as the critical link between adipose tissue and the reproductive system, indicating whether adequate energy reserves are present for normal reproductive function. Future interventional studies involving leptin administration are expected to further clarify this role of leptin and may provide new therapeutic options for the reproductive dysfunction associated with states of relative leptin deficiency or resistance.     

Endocrine disorders in pregnancy.

Disorders of the pituitary gland such as diabetes insipidus, pituitary adenomas, and hyperprolactinemia, disorders of the thyroid gland such as Graves' disease and hypothyroidism, and diseases of the adrenal gland such as adrenocortical insufficiency and Cushing's syndrome can complicate pregnancy. The goals of this article were to provide a basic scientific understanding of the normal function of these endocrine glands, their pregnancy-related changes, and suggestions for diagnosis and treatment of maternal and fetal endocrine disorders during pregnancy. Antenatal recognition and appropriate management of the disorders that especially affect the fetus (i.e., maternal Graves' disease, fetal hypothyroidism, and congenital adrenal hyperplasia) is essential in order to prevent fetal and neonatal morbidity and mortality.     

Expression of CRH, CRH-related peptide and CRH receptor in the ovary and potential CRH signalling pathways

Capacity to cope with stress is crucial for survival and also reproduction. The stress response differs in the various parts of an organism. Central corticotropin-releasing hormone (CRH) has been identified to be the main stress regulator. In the reproductive system, stress has a deleterious effect on reproduction and CRH is associated with dysfunction of the reproductive endocrine axis. Members of the CRH family have been detected in different reproductive organs of males and females. Ovarian CRH is probably involved in steroid biosynthesis and inflammatory like processes, ovulation and luteolysis. These effects are mediated via the CRH receptors CRH-R1 and CRH-R2. CRH-Rs are G protein-coupled receptors that drive different signalling pathways in the cell. In human, ligands for these receptors are CRH, urocortin 1, stresscopin-related peptide and stresscopin. This review gives an overview on the expression of the CRH family members in the ovary of mammals. Furthermore, potential CRH-induced signalling mechanisms in the ovary will be introduced.     

Influence of occupational vibration on the female reproductive system and function

The relevant literature on the effects of occupational vibration was analyzed in order to obtain information concerning a possibly health risk on the female reproductive organs Vibration exposure can probably contribute to the pathogenesis of disorders of female reproductive organs (decrease in uterine blood flow, menstrual disturbances, and anomalies of position) and disturbances of pregnancy (abortions, stillbirths). Experimental animal studies on the reproduction function suggest harmful effects on the fetus, and dystrophic and morphological changes in the uterus and ovaries in animals.     

Autoimmunthyreoiditis und assistierte Reproduktion

Autoimmune thyroid diseases have an impact on fertility in both genders at different reproductive levels. This may affect menstrual disorders, miscarriage rates and sperm quality. The basic endocrine testing should therefore include a thyroid stimulating hormone (TSH) determination. Drug therapy of autoimmune thyroid disease improves the prospects of a reproductive medical treatment and helps to reduce the risk of miscarriage. Evidence of loss of libido and impotence in men should also be tested by a thyroid gland investigation.     

Obesity and assisted reproductive technology outcomes

Obesity is a rising health problem in Western societies. It has been related to increased morbidity and mortality rates due to several pathologies. In the field of gynaecology and reproduction, obesity is associated with menstrual disorders, hirsutism, infertility, miscarriage and obstetric complications. It is known to impair human reproduction through different mechanisms such as insulin resistance, hyperandrogenism and elevated leptin levels. Weight management and dietary intervention can reverse this situation and improve reproductive function. Obesity can also impair the outcome of assisted reproductive technologies. The lower probability of a healthy live birth described in obese women seems to be the result of a combination of lower implantation and pregnancy rates, higher preclinical and clinical miscarriage rates and increased complications during pregnancy for both mother and fetus. Studies performed in infertile women undergoing assisted reproduction technologies indicate that the ovary plays a leading, but not exclusive, role in the fertility prognosis of these patients. The endocrine and metabolic environment may affect oocyte quality and, therefore, embryo development, implantation and pregnancy outcome. The endometrium seems to play a subtle role in the more negative reproductive outcome of obese women, according to recent studies based on the ovum donation model.     

Method and evaluation of hormone assays in practical obstetrics and gynecology

Hormone assays are very important in obstetrics and gynecology. Today, I want to talk about how to measure hormones and how to evaluate the data obtained for therapeutic purposes. In humans, there are two mechanisms of control, neural control and endocrine control. Generally speaking, the neural system controls organs directly via various neurotransmitters, while the endocrine system controls organs by hormones transported in the blood. In fact, recent progress in hormone research has shown that this concept should be modified, because some hormones act as neurotransmitters or regulate other cells or even endocrine cells themselves in the same organ. But I shall not go into this. Today's lecture is focused on hormones that are closely related to clinical obstetrics and gynecology. The hormones that are important are those in females, reproduction, and pregnancy, and tumors. First, and most important, is that patients acquire femininity in the physiological and psychological sense by hormones. The hormones closely related to this are estrogens and pituitary hormones. For reproduction, cyclic hormonal change is important. In the reproductive period, women have menstruation and ovulation along with cyclic changes of ovarian and pituitary hormones. After conception, various kinds of hormones, including hCG, HPL and estriol, are secreted from the feto-placental system. These hormones are used clinically as a markers of placental function. Hormones also have important roles in oncology. hCG is an excellent marker of trophoblastic diseases. Endometrial cancer is expected respond to large doses of progestins if they have progesterone receptors. There are three types of hormone assays, biological assays, immunological assays and chemical assays.(ABSTRACT TRUNCATED AT 250 WORDS)     

Insulin-like growth factors and their binding proteins: Potential relevance to reproductive physiology

Cyclic ovarian follicular development is a complex process that involves proliferation, differentiation, and death of follicle cells. Gonadotropins produced by the pituitary gland have a central role in the regulation of these processes. In addition, a wide range of paracrine and autocrine factors produced in the reproductive organs have been proposed as regulators of reproductive functions. Components of the insulin-like growth factors (IGF) system are widely expressed in the female reproductive tract. The IGFs and their binding proteins play a significant role in several processes of reproductive physiology, including ovarian follicular development, oogenesis and oocyte maturation, ovulation, luteal function, follicular atresia, and testicular function. The majority of these physiological actions of the IGFs are believed to occur via activation of the IGF-I receptor, although the IGF-I effects are modulated by IGF binding proteins (IGFBPs). As much of the data obtained to date have been in the rodent reproductive organs, it may not be possible to directly extrapolate the results to the primate organs. There is a distinct species-difference in the gene expression and functional roles of the IGF-IGFBP system in reproductive organs. However, the disturbance of the IGF-IGFBP system in human reproductive physiology may lead to anovulation, disorders of androgen excess, infertility associated with implantation failure, and male infertility. Further research is needed in domestic animals to determine if manipulation of the IGF-IGFBP system may result in improved reproductive efficiency. As our understanding of the IGF-IGFBP system increases, the uses of human recombinant IGF peptides and IGFBPs as clinical therapy for disease states is becoming a reality. (Reprod Med Biol 2003; 2 : 1–24)     

高浓度雄激素诱导KNDy神经内分泌紊乱在多囊卵巢综合征发病机制中的研究进展

多囊卵巢综合征（polycystic ovary syndrome,PCOS）是全世界女性最常见的生殖障碍性疾病之一,其症状主要表现为排卵、内分泌和代谢异常。尽管PCOS发病机制尚未明确,但是目前越来越多的研究证明高浓度雄激素诱导的神经内分泌紊乱在PCOS的发病中发挥作用,而下丘脑区域的KNDy神经元对女性的生殖功能有着重要的调控作用。近年研究发现,高浓度雄激素可能改变下丘脑区域KNDy神经元网络对促性腺激素释放激素的调节,从而干扰下丘脑-垂体-卵巢/肾上腺/脂肪细胞轴,使下游靶器官生成更多的雄激素即雄激素的恶性循环,加重PCOS的症状。因此,或许可通过在关键发育窗口期降低雄激素对神经内分泌的影响、恢复类固醇反馈的敏感性以及调整促性腺激素释放激素的分泌,进而使黄体生成素/卵泡刺激素（luteinizing hormone/follicle-stimulating hormone,LH/FSH）脉冲正常化来治疗PCOS。     

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.     

Usefulness of monitoring fertility from menarche

The concept of the ovarian cycle as a continuum considers that all types of ovarian activity encountered during the reproductive life are responses to different environmental conditions in order to ensure the health of the woman. During the normal ovulatory cycle, a series of sequential events have to occur in a highly synchronized manner. Fertility awareness is useful in helping women to identify the different stages of their reproductive life cycle. Fertility awareness is also a valuable tool in helping women to identify gynecological disorders. Persistence of irregularities within the mucus patterns and the menstrual cycle should be of concern to women presenting with these problems. These irregularities may be due to obstetrical, endocrine, gynecological or iatrogenic disorders. Insight into early pregnancy complications, ovulatory dysfunction and pelvic inflammatory disease can be ascertained from abnormalities within the menstrual cycle and mucus pattern. Thus, fertility awareness will also enable the recognition and early treatment of several metabolic, endocrine and infectious diseases.     

Investigation and treatment of primary amenorrhoea

The diagnosis and management of adolescent gynaecological conditions demands the need for dedicated teams to manage this complex group of transitional population between pediatric and adult age group. Primary amenorrhoea is one such condition that can be caused by genetic, endocrine or structural disorders during the development of reproductive organs or may be constitutional in nature. Investigations should be offered in stepwise manner with appropriate counselling, keeping the adolescent's psychological development in mind. It is important to recognize the spectrum of normalcy before deciding to investigate the abnormal. Treatment depends on the cause with importance on the immediate and long term wellbeing of the individual.     

Endokrine Disruptoren

Background

We are constantly exposed to a cocktail of substances that could act as endocrine disruptors. Experiences with substances like diethylstilbestrol have proven that the female reproductive organs can be damaged irreversibly by exposure to exogenous hormones during sensitive developmental stages. It is therefore necessary to address this important issue.

Objectives

The adverse effects of endocrine disruptors on the female reproductive organs are summarized. In addition, special aspects of the toxicity of these substances are identified.

Materials and methods

Selected literature on the adverse effects of endocrine disruptors on female reproductive organs was screened and evaluated.

Results

The majority of findings on the adverse effects of endocrine disruptors on the female organism are derived from animal studies. Observed toxicities affect all female reproductive organs (ovaries, uterus, vagina) and the timing of sexual maturation. The effects include polycystic ovary syndrome, altered cycliscity, endometriosis, pregnancy complications, and uterine fibroids. Importantly, the damage does not usually manifest directly after exposition, but after a considerable temporal interval.

Conclusion

Exposure to endocrine disrupters can damage the female reproductive organs. Embryos, fetuses, and newborn babies are much more sensitive than adult women. The extent to which our health is affected by the continuous intake of low quantities of various endocrine disrupters from the environment is very difficult to estimate. Endocrine disruptors therefore remain in the focus of toxicological research.

     

Inhibins, activins, and follistatin in the aging female and male

Dimeric inhibins, activins, and follistatin (FS) were all initially characterized as reproductive endocrine hormones that regulate follicle-stimulating hormone (FSH) secretion. This model, however, has expanded under the weight of current medical evidence. Activin appears to play a central auto/paracrine role in reproductive and nonreproductive tissues. Inhibin and FS each have important counterregulatory functions in activin signaling. With reproductive aging, inhibin B declines along with the follicular pool and disturbs the dynamics of the normal menstrual cycle of midreproductive age. The loss of inhibin restraint of FSH secretion appears to be the initiating endocrine event that leads to menstrual cycle shortening and some of the hormonal unpredictability of the late reproductive years. It may also be related to the decline in fertility that occurs in reproductive aging. In men, inhibin B is an excellent marker for gonadal competence, and the decline of inhibin B with age reflects decreased gonadal reserve in both sexes. Circulating activin increases with aging, but its effect on reproduction in women and men is not clear. FS does not appear to change greatly with aging in men or women. The age-related fluctuations in this delicately balanced regulatory triad influence reproductive capacity and the sequelae of chronological aging. Elucidation of the molecular pathways responsible for the action of these hormones may allow closer integration with their current conceptual roles in aging.     

Drug abuse and reproduction

It is clear that a number of CNS agents, including drugs of abuse, can inhibit reproductive function. Figure 1 shows the chemical diversity of some of the drug groups that affect reproductive hormones. Their structural dissimilarity to the steroid hormones is also readily apparent in the figure. These chemically diverse drugs share an important pharmacologic property: they are highly potent neuroactive drugs, and they can disrupt hypothalamic-pituitary function. Although it is frequently difficult to distinguish between direct drug actions on the hypothalamic-pituitary axis and subsequent effects on gonadal hormones and sex accessory gland function, the distinction is an important one. Most neuroactive drugs produce only transient effects on the central nervous pathways necessary for normal gonadotropin secretion. The disruptive effects of these drugs are likely to be transient and completely reversible, and tolerance to the inhibitory drug effects may occur even with continued drug use. Under these circumstances, normal adults may experience only subtle changes in sexual function. However, individuals with compromised reproductive function may exhibit major problems. It is also likely that adolescents may be at substantial risk for reproductive damage from these neuroactive drugs since the endocrine events associated with puberty are dependent on the normal development of the hypothalamic-pituitary axis.     

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.     

The pleiotropic effects of excessive luteinizing hormone secretion in transgenic mice

Luteinizing hormone (LH) is member of the glycoprotein hormone family of gonadotropins, which also includes the highly related human chorionic gonadotropin and follicle-stimulating hormone. The necessity of these factors for sustaining human fertility has been known for decades. In addition, elevated serum levels of LH have been associated with polycystic ovarian syndrome, suggesting that the appropriate balance of LH is critical for maintaining reproductive function. To dissect the biological consequences of aberrant LH signaling in vivo, several genetically engineered mouse models have been developed that overexpress LH or have increased LH signaling. These models underscore the importance of tightly regulated LH levels for normal reproductive function, and reveal novel roles for LH and gonadal hormones in tumorigenesis of multiple tissues, including the ovary, mammary gland, and pituitary. Thus, mice with altered LH signaling provide valuable tools in understanding normal reproduction and various pathological conditions.