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.     

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.     

Growth hormone: a reproductive endocrine-paracrine regulator?

Growth hormone (GH) is not classically considered as a reproductive hormone, although a vast literature indicates that it has roles in reproductive function. It is required for sexual differentiation and pubertal maturation and it participates in gonadal steroidogenesis, gametogenesis and ovulation. GH is also required for fetal nutrition and growth during pregnancy and for mammary development and lactation. Although some of these roles reflect the action of GH on the secretion and action of LH and FSH (Chandrashekar and Bartke, 1998), they also reflect direct actions of GH and indirect actions mediated through the local production of insulin-like growth factor I. Moreover, as GH is produced in gonadal and mammary tissues, these actions may reflect local autocrine or paracrine actions of extrapituitary GH, as well as the endocrine actions of pituitary GH. The roles of GH in reproductive function are considered in this review.     

Stress and the female reproductive system

The hypothalamic-pituitary-adrenal (HPA) axis, when activated by stress, exerts an inhibitory effect on the female reproductive system. Corticotropin-releasing hormone (CRH) inhibits hypothalamic gonadotropin-releasing hormone (GnRH) secretion, and glucocorticoids inhibit pituitary luteinizing hormone and ovarian estrogen and progesterone secretion. These effects are responsible for the "hypothalamic" amenorrhea of stress, which is observed in anxiety and depression, malnutrition, eating disorders and chronic excessive exercise, and the hypogonadism of the Cushing syndrome. In addition, corticotropin-releasing hormone and its receptors have been identified in most female reproductive tissues, including the ovary, uterus, and placenta. Furthermore, corticotropin-releasing hormone is secreted in peripheral inflammatory sites where it exerts inflammatory actions. Reproductive corticotropin-releasing hormone is regulating reproductive functions with an inflammatory component, such as ovulation, luteolysis, decidualization, implantation, and early maternal tolerance. Placental CRH participates in the physiology of pregnancy and the onset of labor. Circulating placental CRH is responsible for the physiologic hypercortisolism of the latter half of pregnancy. Postpartum, this hypercortisolism is followed by a transient adrenal suppression, which may explain the blues/depression and increased autoimmune phenomena observed during this period.     

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.     

The effect of hormones on endometriosis development

Endometriosis is a common gynecological condition in which tissue that is histologically similar to the endometrium with glands and/or stroma grows outside the uterine cavity and can lead to pelvic pain, dysmenorrhea and infertility. Many aspects of female reproductive function are strongly influenced by genetic factors and numerous studies have attempted to identify susceptibility genes for disorders affecting female fertility such as endometriosis. The importance of steroid hormones on endometriosis is unquestionable. The disease is most prevalent in women of reproductive age and regresses after menopause and its occurrence before menarche has not been reported. Sex steroids, estrogen and progesterone, are mainly produced in the ovaries and they regulate the growth of endometrial tissue, basically by stimulating and inhibiting cell proliferation, respectively. In addition, estrogen plays an important role in the regulation of cyclic gonadotropin release and in folliculogenesis. Numerous studies have been conducted to demonstrate the interaction of hormone and their receptors with endometriosis with conflict results. Besides, environmental chemicals, known as endocrine disruptors, have the capacity to mimic, block or modulate the endocrine system through the interaction with steroidal receptors. Recently evidences have proposed a putative role for ubiquitous environmental contaminants in the occurrence of endometriosis. Here, we reviewed significant articles regarding the interaction among endometriosis, hormones and genetic polymorphic variants.     

多囊卵巢综合征遗传易感性的研究进展

多囊卵巢综合征(PCOS)是一种生殖功能障碍与糖代谢异常并存的内分泌紊乱性疾病,是导致女性不孕最常见的原因之一,其病因至今尚未明确。目前认为,PCOS复杂的临床表现和生化特征是诸多基因和环境因素共同作用的结果,其生化特征提示其发病与参与甾体激素合成与作用的基因、参与胰岛素分泌和作用的基因、参与促性腺激素作用及调节的基因及炎症因子基因相关。因此,对PCOS的遗传易感性研究将有助于进一步揭示其发病机制。     

Hormone-dependent gynaecological disorders: a pathophysiological perspective for appropriate treatment

Hormonal changes are involved in several gynaecological disorders. Correct functioning of the hypothalamus-pituitary-ovarian (HPO) axis is critical for ovulatory function, as well as the growth and differentiation of uterine tissue (myometrium and endometrium). However, the correct functioning of other endocrine glands (thyroid, adrenal cortex, pancreas) is also crucial for correct reproductive function. Genes and environmental factors have an influence on women's fertility through their effect on hormonal function. Consequently, dysfunction of the HPO axis and/or other endocrine systems may cause infertility and gynaecological disorders. The pathogenetic basis can be used to help make the correct clinical decision for treating these diseases. Disturbances related to the menstrual cycle, i.e. amenorrhoea, polycystic ovary syndrome (PCOS) and premenstrual syndrome (PMS), have a close correlation with hypo- or hypersecretion of hormones of the HPO axis. The roles of hypothalamic neurohormones and neurotransmitters in the various forms of amenorrhoea and PMS are well established. PCOS has a complex endocrine/metabolic origin, so a variety of hormonal treatments have been proposed. Hormone derangement has also been proposed as the cause of endometriosis and uterine fibroids. These disorders do not have hyper- or hyposecretion of reproductive hormones, but hyperactivity of oestrogen receptors coupled with a genetic predisposition. The relevance of the endocrine changes is confirmed by the clinical effectiveness of hormonal treatments. In order to establish the correct treatment approach in gynaecological disorders, it is important to understand the endocrine pathophysiology.     

Endocrine disorders and medically assisted procreation

A normal endocrine environment is imperative to maintain normal reproduction in women. The major endocrine organs that play a part in the reproductive system include hypothalamic pituitary axis, adrenal gland, thyroid gland, and the ovary. Each endocrine organ is in close communication and relationship with one another. Any endocrine disorders that significantly affect any of these organs would disrupt reproduction resulting in infertility. In this review, we will provide an overview of the common endocrine disorders and the available medical management including assisted reproductive technology (ART) and hormonal supplementation to overcome the endocrine disorders in order to achieve fertility for the female patients.     

Ghrelin and motilin levels in hyperemesis gravidarum

Purpose

Ghrelin, an endogenous ligand for the growth hormone secratogogue receptor, and its receptors are found in the reproductive organs and placenta. Motilin is produced from the endocrine cells of the duodeno jejunal mucosa and considered to be a regulator of interdigestive migrating contractions. Aim of this study is to investigate ghrelin and motilin levels in patients with hyperemesis gravidarum.

Methods

A total of 56 patients with singleton pregnancies in the first trimester were recruited in the study, 39 with hyperemezis gravidarum and 17 normal pregnant women. Patients with medical complications and body mass index <18 or >25 were excluded. Fasting plasma ghrelin and motilin concentrations were measured. Fasting blood glucose, liver enzymes, blood urea nitrogen, creatinin, estradiol, progesterone, human chorionic gonadotropin, and thyroid function tests were also investigated.

Results

Ghrelin levels were significantly higher in patients with hyperemesis group than the normal pregnant women (p = 0.025). Serum estradiol levels were also higher in the hyperemesis group (p = 0.001). No significant difference was observed in plasma motilin levels between the two groups. In correlation analyses, maternal ghrelin was positively correlated with estradiol (r = 0.29, p = 0.029) in the whole cohort.

Conclusion

There are a few studies about the course of circulating ghrelin levels during human pregnancy. Ghrelin administration increases food intake through central mechanisms but its effects on appetite in relation to human pregnancy is unknown. The increased levels of ghrelin in hyperemesis gravidarum might be a compensatory mechanism to restore the energy metabolism of the pregnant women.     

KNDy神经元在女性生殖内分泌中的研究与应用

Kisspeptin/神经激肽B/强啡肽(kisspeptin/neurokinin B/dynorphin,KNDy)神经元是Kisspeptin神经元的一个亚组,是性激素负反馈的靶细胞,它产生神经激肽B(Neurokinin B,NKB)和强啡肽(Dynorphin A,Dyn),NKB起刺激作用,Dyn起抑制作用...     

Alteration of ghrelin/obestatin ratio in adolescence with polycystic ovarian syndrome

Ghrelin, an endoggenous for the growth hormone secretagogue receptor, has been shown to participate in the regulation of energy homeostasis and pituitary hormone secretion. Obestatin, encoded by the same gene as ghrelin, is described as a physiological opponent of ghrelin. Ghrelin and obestatin are altered in polycystic ovary syndrome (PCOS), which is characterized by insulin resistance and pituitary hormone secretion disorder. The aim of this study was to evaluate ghrelin/obestatin imbalance in relation to insulin resistance and pituitary hormone in adolescence with PCOS. This restrospective case–control study included 33 adolescence with PCOS and 38 control adolescence. Ghrelin and obestatin concentrations in serum were determined by RIA, and the serum fasting glucose and Insulin were determined by the glucose oxidase color method and INS-EASIA. The serum LH and FSH were measured by highly specific hemiluminescence immunoassays. We found that the serum ghrelin levels and ghrelin/obestatin ratio were significant lower in PCOS group than in control group, and the serum obestatin levels were significant higher in PCOS group than in control group. The ghrelin/obestatin ratios were negatively correlation with LH/FSH ratio and insulin resistant index in PCOS group. The findings of this study suggest that ghrelin/obestatin imbalance may play a role in pathogenesis of adolescent PCOS.     

The role of the leptin in reproduction

PURPOSE OF REVIEW: Since its discovery in 1994, leptin has appeared to be a pleiotrophic hormone, governing energy homeostasis and affecting many tissues in the body. Numerous pieces of evidence have accumulated showing that leptin potentially plays an important role in the control of the reproductive function. RECENT FINDINGS: This review presents the major concepts for the role of leptin in the modulation of reproductive function. As a marker of the nutritional status, leptin affects the hypothalamo-pituitary-gonadal axis, regulating gonadotrophin-releasing hormone and luteinising hormone secretion, and appears to be a permissive factor in the onset of the puberty. This protein and its receptor have been found in the reproductive tissues, indicating that this system could be also implicated in several processes such as embryo development, implantation and pregnancy. Moreover, disorders of the leptin system have been related to some reproductive pathologies such as pre-eclampsia and polycystic ovary syndrome. However, controversy surrounds several aspects of the action of leptin in reproduction that require a deeper investigation of this system. SUMMARY: Results to date suggest that this system could be implicated in important reproductive processes such as embryonic development and implantation. Moreover, understanding the role of leptin might be useful for new treatments in reproductive pathologies.     

Polymorphisms of anti-Müllerian hormone signaling pathway in healthy Singapore women: population differences,endocrine effects and reproductive outcomes

In order to study the association of genetic polymorphisms of anti-Müllerian hormone (AMH) signaling pathway with endocrine changes and pregnancy outcomes, a total of 213 women of reproductive ages were recruited according to our inclusion and exclusion criteria between November 2011 and September 2014 in Singapore. Genotyping studies were performed using a minor groove binder primer/probe Taqman assay. The allele frequencies of the AMH Ile⁴⁹Ser and AMHR2 ?482A?>?G polymorphisms were analyzed in relation to female reproductive hormone levels, ovarian parameters, menstrual cycle lengths and pregnancy outcomes. AMH Ser allele frequency and AMHR2 G allele frequency of our Singapore population were compared with those of other populations reported in HapMap. The genotype distributions and allele frequencies for the AMH Ile⁴⁹Ser and AMHR2 ?482A?>?G polymorphisms were not associated with estradiol (E2) levels, ovarian parameters, menstrual cycle length, or pregnancy outcomes in our cohort. Our findings suggest that genetic variants in the AMH signal transduction pathway have population differences but do not appear to have significant effects on ovarian, endocrine, metabolic parameters and reproductive outcomes.     

Inhibins, activins and anti-Müllerian hormone: structure, signalling pathways, roles and predictive value in reproductive medicine

Anti-Müllerian hormone (AMH), inhibins and activins are members of the transforming growth factor (TGFbeta) superfamily and are known to have a variety of actions concerning reproduction, hormonogenesis, development processes and differentiation. Inhibins and activins are dimeric glycoproteins that are defined by their actions on the pituitary gonadotroph cells. AMH, inhibins and activins have a vast array of actions usually exerted through paracrine and endocrine mechanisms. The recent availability of specific inhibin assays has demonstrated that inhibin B is the relevant circulating inhibin form in the human male. Inhibin B seems to be a useful marker of spermatogenesis, but serum and seminal inhibin B levels are not predictive parameters for the selection of azoospermic men as candidates for testicular sperm extraction (TESE). AMH in seminal plasma may be important for sperm production, and is a good marker for sertoli cell development. It might be the only one seminal marker of spermatogenesis in non-obstructive azoospermia. Nevertheless, many of these studies were carried out with small patient numbers, and consequently must be interpreted with caution. In women ongoing assisted reproductive therapy (ART), day 3 inhibin B and AMH levels predict the number of oocytes retrieved, but cannot predict likelihood of pregnancy. Further studies are needed to determine if AMH and inhibin predict ART outcomes better than classical parameters (age, FSH levels and follicular ultrasonography). AMH and inhibin are also specific markers of Sertoli- and granulosa-cell origin in gonadal tumors.     

Menstrual bleeding, hormones, and the menopausal transition

The perimenopause represents a time of great variability in reproductive hormone dynamics and menstrual cycle characteristics, but age-related changes begin prior to this. These changes include a gradual increase in follicle stimulating hormone (FSH) levels, a gradual shortening of mean cycle length, and a decline in the number of ovarian follicles. The onset of perimenopause is thought to occur with the first break in menstrual cycle regularity. With the onset of cycle irregularities, hormone concentrations exhibit large increases in variability and unpredictability, rather than following a gradual trend with the approach of menopause, the final menstrual period. Abrupt spikes in gonadotropins and considerable fluctuations in estradiol and inhibin levels have been observed. Variability is the norm in the perimenopause, with hormonal fluctuations contributing to the visible signs of menstrual cycle and bleeding irregularities. To date there is no single endocrine indicator to serve as an adequate marker of menopausal status. This paper provides a review of research to date on patterns of reproductive hormones and menstrual bleeding during the menopausal transition. An understanding of such patterns can contribute to a better ability to distinguish "normal" transitional events from more serious pathology.     

Endocrine effects of danazol in the treatment of endometriosis

The effects of danazol therapy on circulating gonadotrophins, oestradiol and sex hormone-binding globulin (SHBG) binding capacity have been studied in eight patients with endometriosis. There was a significant rise in luteinizing hormone (LH) in the first week of treatment with a fall in oestradiol levels. There was a marked fall in SHBG in the first week which continued up to 4 weeks. It is concluded that danazol is not 'anti-gonadotrophic' as frequently claimed and that its therapeutic actions, side effects and the endocrine changes could be explained by an effect on SHBG production. The rationale of its use in other conditions requires reconsideration.     

Adrenal response to adrenocorticotropic hormone stimulation in patients with premenstrual syndrome.

Several studies have been performed during recent years to investigate the existence of a possible endocrine cause for premenstrual syndrome (PMS); the results reported are often discordant. Great interest has been raised around allopregnanolone, which could be involved in the determination of mood disorders reported by PMS patients. During the luteal phase, lower levels of this hormone have been detected in PMS patients. The aim of our study was to evaluate estradiol, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), androstenedione, total and free testosterone, cortisol, pregnenolone and allopregnanolone levels in 20 patients suffering from PMS and to compare them with those found in 20 fertile healthy women in the follicular and the luteal phases. Adrenocorticotropic hormone (ACTH) tests after dexamethasone suppression were performed in 10 patients of each group during the follicular and the luteal phases. In the PMS group, significantly lower allopregnolone levels were found in the luteal phase, while progesterone was lower in the PMS group in both phases. In the PMS group, higher free testosterone levels were found during the luteal phase and higher DHEA levels in both the follicular and the luteal phases. The present data confirm reduced allopregnanolone levels in the luteal phase in PMS patients, together with higher levels of DHEA and free testosterone. It is possible to conclude that, in addition to the previously described reduced luteal secretion of allopregnanolone, the adrenal gland production of this steroid in PMS sufferers is also impaired in the luteal phase. Considering the specific actions of these hormones on the control of mood and behavior, this specific hormonal milieu may contribute to the cyclic occurrence of anxiety, aggressiveness and irritability reported by PMS patients.     

生活方式干预疗法在多囊卵巢综合征治疗中的作用

多囊卵巢综合征（PCOS）是一种多起因、异质性的女性内分泌系统疾病,影响患者生殖及代谢,并发心血管病及精神心理问题风险增高。生活方式干预疗法能够减轻月经紊乱、多毛痤疮等症状并有利于治疗不孕,延缓远期代谢综合征的发生,改善生活质量。因而成为PCOS患者尤其合并肥胖者重要的一线治疗方案。