雌激素受体在人类垂体腺瘤中的表达

目的检测雌激素受体(estrogen receptor,ER)在人类不同类型激素垂体腺瘤中的表达,探讨垂体腺瘤中分泌不同类型激素的腺瘤细胞与ER免疫组化阳性细胞之间的关系.方法采用免疫组化S-P法对53例垂体腺瘤标本进行激素分型,检测垂体腺瘤中ER蛋白的表达.采用免疫组化双标法检测多激素分泌型垂体腺瘤中垂体激素合并ER表达的情况.结果53例垂体腺瘤标本中,部分PRL(5/7)、FSH(2/3)、LH(1/1)单激素腺瘤及部分多激素腺瘤有ER蛋白表达,而全部GH、ACTH、TSH单激素腺瘤均无ER蛋白表达,4例无功能腺瘤无ER蛋白表达.在33例多激素型垂体腺瘤标本中,22例有ER蛋白表达,其中PRL ER双标染色阳性标本10例、LH ER双标染色阳性标本9例、FSH ER双标染色阳性标本7例、GH ER双标染色阳性标本2例,33例标本的ACTH ER和TSH ER的双标染色均为阴性.结论垂体腺瘤患者的性别不影响肿瘤组织中ER蛋白的表达.垂体腺瘤中,分泌PRL、LH或FSH的垂体腺瘤细胞可表达ER;分泌ACTH或TSH的垂体腺瘤细胞不表达ER;分泌GH的垂体腺瘤细胞是否表达ER可能与该垂体腺瘤是否同时分泌PRL有关.ER在PRL、LH及FSH垂体腺瘤细胞的发生、发展中发挥作用.     

下丘脑—垂体的增龄性变化

动物实验与临床观察揭示,衰老过程中,下丘脑-垂体在结构和功能上发生了重要的改变。下丘脑生长抑素分泌增高,5～HT能神经活性增高,多巴胺和儿茶酚胺能神经活性减低。垂体后叶对ADH的调节异常。垂体前叶GH分泌减少,PRL、TSH、ACTH、LH及FSH分泌紊乱。垂体腺瘤形成。此外,下丘脑-垂体神经递质受体或激素受体减少。这些变化最终导致下丘脑-垂体功能减退及机体的老化。     

老化与腺垂体激素

老年人腺垂体的形态特征表现为斑性纤维化增多、局灶性坏死、血管变异、铁质沉积以及微腺瘤形成,同时整个体积也略为变小。但腺垂体功能,即腺垂体激素分泌与合成的变化究竟与老化之间存在怎样的关系,目前仍在探讨之中,并取得了一些新的进展,下面就其中几个重要激素的变化作一简述。促性腺激素(LH、FSH) 研究表明,当年龄超过50岁以上时,血液中LH和FSH的基础水平随年龄增长而增加,同时检测到尿中排出的具有生物活性的促性腺激素也明显增加,现认为,血浆中LH基础水平的增加有三个原因:(1)Leydig细胞功能衰竭;(2)腺垂体对雄     

垂体前叶病变性闭经

垂体前叶即腺垂体,以垂体门脉系统与下丘脑构成下丘脑-腺垂体系统,直接接受下丘脑神经内分泌激素的调控,可以分泌FSH、LH、PRL、TSH、ACTH和GH六种激素,即性腺六项。垂体前叶病变是引起闭经的重要组成部分。由于腺垂体器质性病变或功能失调引起其分泌激素异常,尤其是促性腺激素分泌异常,进而影响下游卵巢功能,引起闭经。     

5-羟色胺与雌性大鼠生殖系统老化

哺乳动物的下丘脑—垂体—卵巢系统随增龄逐渐发生变化,表现为下丘脑 5—羟色胺(5-HT)能神经活性的增强和儿茶酚胺能[多巴胺(DA)、去申肾上腺素(NE)]神经活性的减弱,这些变化影响了垂体促性腺激素[促黄体生成素(LH)和卵泡刺激素(FSH)]的释放;进一步影响卵巢甾体激素的分泌。因此甾体激素对垂体促性腺激素的反馈作用也随之变化;并引起一系列神经内分     

贵州省地方性克汀病垂体—性腺系统功能对LHRH兴奋试验的反应

在已经加碘得到控制的碘缺乏性疾病病区,观察了地方性克汀病垂体--性腺系统对促黄体激素释放因子(LHRH)试验的反应。结果:男性克汀病病人组血清黄体生成激素(LH)和卵泡刺激素(FSH)基础值显著高于对照组,但其血清睾酮(T)值则显著低于对照组。静脉注射 LHRH100μg15分钟后,克汀病病人组血清 FSH 反应高于正常人组,LH 反应与正常对照组相似。两组血清 T 值于试验后无显著变化。静脉注射接着静脉滴注 LHRH,克汀病病人组 FSH 反应高于正常人,其 LH 最大增值和反应倍数均低于对照组,正常人组 LH、FSH 呈双相反应,克汀病病人组则无此反应。血清 T,正常人组试验后2-3小时显著升高,克汀病病人组无则显著变化。结果表明克汀病病人不仅有原发性 Leydig 和 Sertoli 细胞功能低下,而且还有垂体促性腺激素储备和再合成功能的减低。     

绝经后妇女持续给予Gn-RH引起垂体促性腺激素分泌的降解调节

单次注射GnRH或其高活性类似物可刺激垂体促性腺激素分泌,但在动物和人类,如持续给予GnRH或其有效类似物,在垂体与性腺水平却引起了自相矛盾的生殖攻能抑制。为了解释这种现象,作者给四个正常的绝经后妇女经静脉持续输注Gn-RH,观察对促性腺激素分泌的影响。 四名正常绝经后妇女年龄53—64岁,住院4天。最初24小时为对照,其后72小时以1微克/分钟的速度持续输注合成GnRH,每4小时抽血用放免法测血清LH、FSH与E_2。输注前LH与FSH基值分别为23±3与94±27毫国际单位/毫升,输注后     

垂体瘤的诊断、鉴别诊断与治疗——常见垂体腺瘤的临床诊断

垂体腺瘤是发生于腺垂体的良性肿瘤，占中枢神经系统肿瘤的10％～20％，是颅内最常见的肿瘤之一。根据免疫组织化学将垂体腺瘤按功能进行分类，主要有激素分泌活性腺瘤和非激素分泌活性腺瘤两大类。前者包括生长激素瘤(GH腺瘤)、催乳素瘤(PRL腺瘤)、促肾上腺皮质素瘤(ACTH腺瘸)、Nelson综合征、促甲状腺素瘤(TSH腺瘤)、促性腺素瘤(FSH和LH腺瘤)；后者包括无功能细胞腺瘤。现将临床比较     

牛卵泡液对切除卵巢母羊GnRH、LH和FSH脉冲分泌的调节作用

给切除卵巢母羊注射活性炭提取的牛卵泡液(n=5)或切除垂体的母羊血清(n=5)后,测定垂体门脉GnRH和外周血LH和FSH。注射牛卵泡液组血浆FSH水平下降50％,而注射去垂体羊血清组无明显改变。两组的GnRH和LH脉冲的幅高和频率相似,表明牛卵泡液抑素选择性的抑制垂体释放FSH,对GnRH分泌无影响。     

肝功能衰竭患者甲状腺激素与垂体激素变化的研究

目的研究肝功能衰竭(hepatic failure,HF)患者甲状腺激素和垂体激素变化及其与HF预后的相关性。方法收集2015年我院HF患者30例、慢性乙型肝炎轻中度患者58例和慢性乙型肝炎重度患者35例。比较各组患者血清甲状腺激素及垂体激素水平。结果HF组血清T3、T4、FT3、TSH、FSH、LH水平显著低于慢性乙型肝炎轻中度组(P0.05),HF组血清T3、T4、FT3、TSH水平显著低于慢性乙型肝炎重度组(P0.05),HF组血清GH水平显著高于慢性乙型肝炎轻中度组GH水平(P0.05)。HF非好转组TSH、FSH、LH明显低于好转组TSH、FSH、LH水平(P0.05)。TSH为HF预后的保护因素。结论 HF时出现甲状腺功能减退,主要表现在T3、T4、FT3及TSH,TSH值是HF的预后指标。而垂体功能也出现异常,主要表现为TSH、FSH、LH、ACTH的下降,GH的上升,由此推测垂体功能异常可能是HF时甲状腺激素分泌异常的原因之一。     

Studies on the feedback regulation of gonadotropin concentrations in male rats. (III). The effects of testosterone and its metabolites on gonadotropin secretion from rat pituitary cells in culture

To determine whether dihydrotestosterone (DHT) or estradiol (E2) exerts negative or positive feedback effects on rat pituitary gland, Testosterone (T) metabolite (T, DHT, 5 alpha-androstane-3 alpha, 17 beta-diol:3 alpha-diol or E2) was added to the cultured pituitary cells. Anterior pituitary glands were obtained from 6-week-old male rats. Pituitary cells were prepared by trypsin digestion and incubated with various concentrations of steroid hormones for 72 h to determine the effects of steroid hormones on basal secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH) after 48 h preculture without steroids. Then 10 nM luteinizing hormone-releasing hormone (LH-RH) with appropriate concentrations of these steroid hormones was added to the pituitary cells in culture and incubated for another 6h to determine the effects of steroid hormones on LH-RH induced gonadotropin release. After the incubation, pituitary cells were lysed with 0.1% Triton X100 to measure the intracellular gonadotropin content. The concentration of LH and FSH was determined by radioimmunoassay. T, DHT and 3 alpha-diol stimulated basal FSH but not basal LH secretion, and inhibited both the release of FSH and LH from cultured pituitary cells during incubations with LH-RH in a dose-dependent fashion. Intracellular content of both FSH and LH were increased, and total FSH and not LH was also increased by the addition of DHT in a dose-dependent manner. E2 did not exert any of such effects on pituitary cells in culture. These studies suggest that 5 alpha-reduced metabolites but not aromatized metabolite of T play an important role on feedback regulation of gonadotropin secretion at pituitary level. DHT directly acts on pituitary gland not only to stimulate the production of FSH but also to suppress FSH and LH secretion induced by LH-RH.     

Hormones in synergy: Regulation of the pituitary gonadotropin genes

The precise interplay of hormonal influences that governs gonadotropin hormone production by the pituitary includes endocrine, paracrine and autocrine actions of hypothalamic gonadotropin-releasing hormone (GnRH), activin and steroids. However, most studies of hormonal regulation of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the pituitary gonadotrope have been limited to analyses of the isolated actions of individual hormones. LHβ and FSHβ subunits have distinct patterns of expression during the menstrual/estrous cycle as a result of the integration of activin, GnRH, and steroid hormone action. In this review, we focus on studies that delineate the interplay among these hormones in the regulation of LHβ and FSHβ gene expression in gonadotrope cells and discuss how signaling cross-talk contributes to differential expression. We also discuss how recent technological advances will help identify additional factors involved in the differential hormonal regulation of LH and FSH.     

FSH secretion predominates in vivo and in vitro in patients with non-functioning pituitary adenomas

OBJECTIVE: Non-functioning pituitary adenomas (NFPAs) are characterised by the lack of symptoms of hormone hypersecretory syndromes but in vitro studies have demonstrated that tumour cells may stain for gonadotrophins and/or their alpha- or beta-subunits. In this study, we aimed to examine the pattern of secretion of LH and FSH from a series of pituitary adenomas cultured in vitro and where data were available to relate the results to pre-operative serum gonadotrophin levels. METHODS: The in vitro secretion of LH and FSH was measured from 46 cultured NFPAs and compared with pre-operative serum gonadotrophin levels in 38 patients. Peritumorous 'normal' pituitary cell cultures from 20 additional pituitary tumour patients were used for comparison with the NFPA group. RESULTS: A median pre-operative LH:FSH ratio of 0.33:1 was found in 38 patients with NFPAs. Preferential secretion of FSH was also documented from media of 46 NFPAs cultured in vitro with a median LH:FSH ratio of 0.32:1. A significant correlation (r = 0.43, P < 0.01) was observed between serum and media levels of FSH but not LH. Peritumorous 'normal' pituitary cells released LH and FSH in a reversed ratio (median LH:FSH ratio = 3.6:1, P < 0.01 compared with NFPAs). CONCLUSIONS: This study has evaluated pre-operative serum gonadotrophin levels and in vitro release of hormones in cultures of surgically removed tissue from patients with NFPAs. The data suggest preferential secretion of FSH occurs both in vitro and in vivo. By demonstrating that NFPAs cultured in vitro reflect the in vivo situation of preferential secretion of FSH, it may be possible in future to perform functional studies using this system to elucidate the cellular and molecular mechanisms involved in the development of an imbalance in gonadotroph cells preferentially overproducing FSH in NFPAs.     

Gonadotrophin-releasing activity of neurohypophysial hormones: I. Potential for modulation of pituitary hormone secretion in rats

Neurohypophysial hormones have been implicated in the control of anterior pituitary function, and oxytocin has been shown to stimulate gonadotrophin excretion and ovarian follicular development in certain species. To determine the role of neurohypophysial peptides in the control of gonadotrophin release, their actions on LH and FSH secretion were analysed in rats in vivo and in vitro. In adult female rats, administration of oxytocin during early pro-oestrus advanced the spontaneous LH surge and markedly increased peripheral LH levels at 15.00 h compared with control animals. In cultured pituitary cells from adult female rats, oxytocin and vasopressin elicited dose-related increases in LH and FSH release. Such responses were not affected by a potent gonadotrophin-releasing hormone (GnRH) antagonist that abolished GnRH agonist-induced release of LH and FSH. Oxytocin did not enhance GnRH agonist-stimulated gonadotrophin release to the same extent as it increased basal secretion, but at low concentrations of GnRH agonist the effects were additive. The gonadotrophin responses to oxytocin and vasopressin were inhibited by the specific neurohypophysial hormone antagonists, [d(CH2)5D-Ile2,Ile4,Arg8]vasopressin and [d(CH2)5Tyr (Me),Arg8]vasopressin. These results provide direct evidence that neurohypophysial hormones can stimulate gonadotrophin secretion through a receptor system distinct from the GnRH receptor. Such a mechanism could represent a complementary hypothalamic control system for long-term modulation of LH and FSH secretion by exerting a basal or tonic influence on gonadotrophin production.     

Quantitative bioassays for measuring biologically functional gonadotropins based on eel gonadotropic receptors

Significant declines in eel stocks have been noted in many parts of the world. Because eel aquaculture is dependent on wild-caught juveniles, there is a need to achieve artificial reproduction. Adult eel maturation is currently induced by repeated injections of purified gonadotropin (human chorionic gonadotropin [hCG]) or pituitary extract. Thus the determination of the biological efficacy and quantification of internal levels of gonadotropic hormones is important for optimizing artificial reproduction protocols. To quantify the plasma levels of biologically functional gonadotropic hormones, we developed a bioassay for luteinizing hormone (LH) and follicle-stimulating hormone (FSH) based on the stable expression of receptors in HEK293 cells of the Japanese eel Anguilla japonica LH (ajLHR) and the European eel Anguilla anguilla FSH (aaFSHR), respectively. Such cells also contain a firefly luciferase reporter gene driven by a cAMP-responsive element (CRE-Luc). We found that the obtained stable cells, with ajLHR, responded linearly to a more than 100,000-fold concentration range of hCG diluted in saline. The cells with aaFSHR showed a linear response to a 1000-fold concentration range of salmon pituitary extract mixed with saline. The biological functionality of the LH and FSH bioassays was validated using hCG, human FSH, and pituitary extracts from salmon, carp and eel. Since the toxins in eel plasma damaged the HEK293 cells, the protocol was adapted to selectively inactivate the toxins by heating at 37°C for 24h. This process successfully enabled the monitoring of hormone levels in blood plasma sampled from hCG-injected eels. In this paper, we describe the development of gonadotropin bioassays that will be useful for improving reproduction protocols in eel aquaculture.     

Evidence for the involvement of hypothalamic dopamine and thyrotrophin-releasing hormone in suckling-induced release of prolactin

The interactions of several mammalian follicle-stimulating hormones and luteinizing hormones with specific gonadotrophin receptors in macropodid marsupial testicular homogenates were investigated with a view to developing radioreceptor assays for marsupial FSH and LH. Testes from Eastern grey kangaroos and tammar wallabies possessed high affinity (dissociation constant congruent to 10(-10) mol/l) saturable receptor sites which were highly specific for LH or FSH. Luteinizing hormone receptor sites bound only highly purified LH preparations (human, ovine and rat) but did not bind highly purified FSH, TSH or prolactin while FSH receptor sites were equally specific for highly purified FSH preparations. These sites demonstrated a degree of species specificity in that marsupial pituitary extracts were relatively more potent in these assays than in assays using gonadotrophin receptors from rat testes. Serum from hypophysectomized female tammar wallabies had little effect on the slope and position of the LH standard curve but significantly depressed the dose-response curve for FSH. For this reason it was not possible to develop a radioreceptor assay for serum FSH using marsupial testicular FSH receptors. However, gonadotrophin receptors from both rat and marsupial testes have been employed in the successful development of radioreceptor assays for marsupial pituitary LH and FSH and marsupial serum LH.     

Immature rat pituitary glands in vitro: age- and sex-related changes in luteinizing hormone releasing hormone-stimulated gonadotrophin release.

Pituitary glands from immature female and male rats aged between 5 and 30 days were incubated in vitro and the effect of LH releasing hormone (RH) on the release of LH and FSH was studied. Pituitary gonadotrophin contents were also measured. Gonadotrophin release showed changes with age as well as sex differences: after LH-RH stimulation the female pattern of release of LH and FSH (expressed per mg pituitary tissue) showed a peak at day 15; the male pattern of LH release was characterized by a steady increase with age, whereas FSH release stayed more or less constant from day 10 onwards. In both sexes the LH:FSH ratio increased with age, both in pituitary gonadotrophin content and in the mixture of gonadotrophins released. It is discussed, that the prepubertal development of pituitary gonadotrophic function might be determined on the one hand by rather autonomous growth processes (more or less similar in female and male hypophyses) and on the other hand by modulating influences of sex steroid hormones, which are different in female and male animals.     

Gonadotropin secretion in vitro by human pituitary null cell adenomas and oncocytomas

Pituitary null cell adenomas and oncocytomas are tumors not associated with clinical or biochemical evidence of hormone excess; morphological studies have not hitherto revealed their origin or the nature of their hormone production, if any. We examined the in vitro secretory activity of seven null cell adenomas and five oncocytomas which caused symptoms of a mass lesion and variable degrees of hypopituitarism. All tumors were classified at the time of surgical resection using immunohistochemistry and electron microscopy. RIA revealed the presence of FSH, LH, and alpha-subunit of pituitary glycoprotein hormones in the culture medium of eight tumors, FSH and alpha-subunit in the medium of one tumor, and TSH, FSH, LH, and alpha-subunit in the medium of three adenomas. Morphological examination of cultured tissues confirmed the presence of tumor resembling those in the initial surgical specimen. Thus, we conclude that null cell adenomas and oncocytomas contain cells that can produce pituitary glycoprotein hormones, and that the majority produce gonadotropins.     

Molecular basis of gonadotropin receptor regulation.

The anterior pituitary hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), act upon the ovary and testis via occupancy of specific cell membrane receptors, resulting in increased cAMP production, steroidogenesis, and expression of differentiation-related genes. Recent cloning of the cDNAs for LH and FSH receptors allows the analysis of mRNA levels for these receptors in gonadal tissues. This review summarizes progress in elucidating the molecular basis of LH and FSH receptor gene regulation in the ovary and testis during different physiologic states.