Pituitary FSH is released by a heterodimer of the beta-subunits from the two forms of inhibin

Inhibin is a gonadal protein that specifically inhibits the secretion of pituitary follicle-stimulating hormone (FSH). Two forms of inhibin (A and B) have been purified from porcine follicular fluid and characterized as heterodimers of relative molecular mass (Mr) 32,000 (ref. 2). Each inhibin is comprised of an identical alpha-subunit of Mr 18,000 and a distinct but related beta-subunit of Mr 13,800-14,700 linked by interchain disulphide bond(s). Throughout the purification of inhibins, we consistently observed two fractions which stimulated the secretion of pituitary FSH. We report here the isolation of one of the FSH-releasing proteins; it has a Mr of 24,000 and its N-terminal sequences up to residue 32 are identical to those of each beta-subunit of inhibins A and B. In the presence of reducing agents, SDS-polyacrylamide gel electrophoresis resolves the FSH-releasing substance into two subunits which are identical in their migration behaviour to the reduced beta-subunits of inhibins A and B. Based on the N-terminal sequence data and Mr of the intact and reduced molecules, we propose that the FSH-releasing substance, which is active in picomolar concentrations, is a heterodimeric protein composed of the two beta-subunits of inhibins A and B linked by interchain disulphide bond(s). The structural organization of the FSH-releasing substance is homologous to that of transforming growth factor-beta (TGF-beta), which also possesses FSH-releasing activity in the same bioassay. We suggest that the substance be called activin to signify the fact that it has opposite biological effects to inhibin.     

Importance of FSH-releasing protein and inhibin in erythrodifferentiation

Inhibin is a hypophysiotropic hormone which selectively suppresses the secretion of pituitary follicle-stimulating hormone. It has been isolated from gonadal fluids and characterized as a protein heterodimer consisting of an alpha subunit and one of two beta subunits (beta A or beta B). FSH-releasing protein (FRP), also named activin, is a dimer consisting of two inhibin beta-chains. A factor from conditioned medium of a leukaemia cell line has been isolated which can induce mouse Friend cells to become benzidine-positive, and which shares a similar N-terminal sequence with porcine FRP. In this report, we find that FRP and inhibin modulate both the induction of haemoglobin accumulation in a human erythroleukaemic cell line, K562, and the proliferation of erythroid progenitor cells in human bone marrow culture. These two proteins could constitute a novel humoral regulatory control of erythropoiesis which would involve two types of related protein dimers with functionally opposite effects.     

Complementary DNA sequences of ovarian follicular fluid inhibin show precursor structure and homology with transforming growth factor-beta

Inhibin, a specific and potent polypeptide inhibitor of the secretion of follicle-stimulating hormone (FSH), of gonadal origin and thus a potential contraceptive, may constitute a missing link in the mechanism controlling the differential secretion of the pituitary gonadotropins. Inhibin-like bioactivity has been reported in various fluids and extracts of testis and in ovarian follicular fluid. Although there have been several attempts to purify inhibin from seminal plasma, purification from follicular fluid has been more successful (refs 14-16; for review see ref. 17). We have previously isolated two forms (A and B) of inhibin from porcine follicular fluid. Each form comprised two dissimilar subunits of relative molecular mass (Mr) 18,000 (18K, referred to here as the alpha-subunit) and 14K (the beta-subunit), crosslinked by one or more disulphide bridge(s). Forms A and B differ in the N-terminal sequence of their 14K subunit. Preliminary structural characterization of porcine and bovine ovarian inhibins shows that they have similar properties. Here, we have used the N-terminal amino-acid sequence data on the subunits of each inhibin to identify cloned complementary DNAs encoding the biosynthetic precursors and report that inhibins are the product of a gene family that also includes transforming growth factor-beta (TGF-beta) and whose structural organization is similar to that of pituitary and placental glycoprotein hormones.     

Inhibin is absent from azoospermic semen of infertile men

There is ample evidence that the secretion of follicle stimulating hormone (FSH) by the pituitary gland is regulated by a nonsteroidal hormone of gonadal origin, termed inhibin. In several species, testicular extracts, gonadal lymph and seminal plasma have been shown to contain proteins which inhibit FSH release; lack of suitable assays for inhibin has, however, prevented clear definition of its physiological significance. Men whose tests show the histological changes of germinal cell failure usually have raised FSH levels in the blood, but may have normal levels of luteinizing hormone (LH) and testosterone. Such patients would thus be predicted to show reduced inhibin production. To test this, we have measured the FSH inhibitory activity of seminal plasma from azoospermic subjects with raised plasma FSH levels. We report here our confirmation of diminished inhibin levels in seminal plasma of these patients, thus providing convincing support for its physiological role as a modulator of FSH production in man.     

Gonadotropin-releasing hormone analogue binds to luteal cells and inhibits progesterone production.

Although gonadotropin-releasing hormone (GnRH) is believed to mediate the hypothalamic control of pituitary gonadotropin secretion, continuous or repeated administration of GnRH or its agonist analogues has been shown to cause paradoxical antifertility effects in several species, including primates. GnRH-induced interruption of reproductive cycles and pregnancy is associated with diminished progesterone production, implying defective function of the corpus luteum. These luteolytic effects have been attributed to the well recognized desensitising actions of elevated luteinising hormone (LH) levels on ovarian LH receptors and steroidogenesis, subsequent to GnRH-induced gonadotropin release from the anterior pituitary. However, treatment with high doses of exogenous LH did not cause suppression of serum progesterone levels during early pregnancy in rats, whereas a highly active GnRH analogue was effective in this regard. These observations suggested that GnRH and its agonist analogues, given in high or sustained doses, can exert a direct action on the ovary that is independent of the pituitary. This hypothesis was further supported by the ability of GnRH and its agonists to inhibit human chorionic gonadotropin (HCG)-induced ovarian and uterine weight gain in hypophysectomised rats and to delay the onset of puberty in intact female rats. Also, GnRH and its agonist analogues have recently been shown to inhibit steroidogenesis induced by follicle-stimulating hormone (FSH) in cultured granulosa cells, confirming the direct action of such peptides on the ovarian follicle. The marked inhibitory effects of GnRH and its agonists on corpus luteum function suggest that these compounds could exert direct actions by binding to specific receptors on luteal cells. The present experiments, which examine the effects of GnRH agonists on luteal steroidogenesis, demonstrate the existence of such actions and their mediation by specific high-affinity receptor sites present in luteal cell membranes.     

抑制素及相关肽

换制素一直被认为是一种性腺激素,它对垂体促性腺细胞FSH的分泌具有一定的负馈调节作用。本文综述了近年来抑制素及其相关肽的最新研究。从抑制素的检测方法到结构描述,从抑制素的产生调节到可能的生物作用,本文都做了详尽的叙述。     

Inhibin beta in central neural pathways involved in the control of oxytocin secretion

Inhibin (I) a gonadal hormone glycoprotein which suppresses follicle-stimulating hormone (FSH) secretion from the anterior pituitary, is a heterodimer consisting of an alpha subunit and one of two distinct beta subunits. S1 nuclease analysis has revealed that RNAs encoding all three subunits (alpha, beta A and beta B) are expressed in rat brain. We report here on the localization, and a potential function, of inhibin beta in the rat brain. A cell group centred in the nucleus of the solitary tract (NTS), a major recipient of visceral sensory information, was stained immunohistochemically with antisera against synthetic fragments of I beta, but not I alpha. The distribution of I beta-stained fibres is consistent with known NTS projections, and includes a prominent projection to oxytocinergic aspects of the magnocellular neurosecretory system.     

采用染料亲和层析的方法纯化卵泡刺激素

采用染料亲和层析、QAE离子交换层析等纯化步骤，从绝经期妇女尿促性腺激素(HMG)粗品中分离纯化获得高纯度卵泡刺激素(FSH)产品，其中FSH的生物活性达到268.1IU／mg，卵泡刺激素与黄体生长素(LH)的活性比值达到259，产品超过欧洲药典对高纯度卵泡刺激素的要求。此工艺FSH的活性回收率高达65％，而且分离纯化步骤少，简单易行，适合于大规模生产。     

锯缘青蟹视神经节FSH和LH的免疫识别

甲壳动物的视神经节含有性腺抑制激素(Gonad inhibiting hormone, GIH),长期以来视神经节被理解为生殖抑制效应.本研究应用脊椎动物卵泡刺激素(Fllicle stimulating hormone,FSH)抗体和黄体生成素(Luteinizing hormone,LH)抗体,从锯缘青蟹(Scylla serrata)视神经节的视外髓、视内髓和视端髓检测到FSH和LH免疫细胞化学阳性反应.锯缘青蟹视神经节中的FSH和LH免疫阳性物质,可能参与了生殖神经内分泌调节.     

动物抑制素的作用机制与技术开发（综述）

抑制素的生理功能不仅是抑制促卵泡素分泌,而且与下丘脑或更高级的中枢神经活动有关。生理剂量的抑制素只影响促卵泡素的分泌,对促黄体素分泌基本无作用。抑制素免疫可显著提高动物体内促卵泡素的浓度,对繁殖季节和非繁殖季节的母畜都有作用。本文综述了抑制素免疫在提早母畜性成熟和提高公畜繁殖力,提高母畜排卵率,与其它生殖激素免疫的比较,牛抑制素亚单位重组产品,抑制素在禽类繁殖上的作用,抑制素水平检测及应用等方面研究进展,并阐明了抑制素技术开发的前景。     

Lactogenic receptor regulation in hormone-stimulated steroidogenic cells

Receptor sites for lactogenic hormones such as prolactin (PRL), human growth hormone (HGH), and placental lactogens, are widely distributed in mammalian tissues, including mammary glands, steroid-secreting cells of the adrenal, testis, and ovary, and target cells of steroid hormone action such as liver, prostrate, and kidney. Although the biological functions of lactogen binding sites remain uncertain, a relationship between prolactin and lipoprotein metabolism is implied by the occurrence of prolactin receptors in steroidogenic cells of the gonads and adrenal, and by the ability of prolactin to increase esterified cholesterol in the testis. Recently, loss of testicular prolactin receptors has been observed following elevation of circulating luteinising hormone (LH) concentrations by the gonadotropin releasing hormone (GnRH) and its agonist analogues. The hormone dependence of lactogen receptor sites in steroid-secreting cells was further analysed in rat testis, ovary, and adrenal glands after treatment with the respective trophic hormones, gonadotropin and ACTH. In each of these tissues, rapid and transient loss of lactogen receptors was observed after trophic hormone stimulation. These findings indicate that increased turnover of lactogen receptors is an important component of the target-cell response, and suggest that prolactin receptors might be involved in the transport of lipoprotein precursors for steroid biosynthesis.     

脊椎动物促性腺激素释放激素的结构、基因表达与调控的研究进展

综述了有关对脊椎动物促性腺激素释放激素的结构、基因表达与调控的研究进展 .阐明促性腺激素释放激素结构多样性 ,功能多样性 ,及其基因表达与调控 ,并对可能的应用前景作简要阐述     

虎纹蛙促性腺激素及其释放激素含量的日变化

利用具有高度特异性的放射免疫测定法,研究了10月份虎纹蛙成蛙脑和脑垂体GnRH、以及脑垂体和血浆GtH含量的日变化,结果表明：雌蛙脑和脑垂体mGnRH含量、以及脑垂体cGnRH-Ⅱ含量都存在有明显的日变化;雄蛙脑垂体和血浆LH水平,以及雌、雄蛙血浆FSH水平也都存在明显的日变化;对各种激素日变化产生的原因进行了探讨.     

奶牛生殖激素浓度与胎次的相关性研究

为探讨奶牛血液生殖激素浓度随不同胎次的变化规律及相关性和回归关系,用ELISA法测定了48头奶牛促卵泡激素(FSH)、促黄体激素(LH)、绒毛膜促性腺激素(β-HCG)、睾酮(T)、孕酮(P)和雌二醇(E2)的浓度,分析了激素浓度胎次间的相关关系和回归方程.结果表明,HCG浓度以第0、1胎为最高和最低(p<0.05);P、LH和E2浓度均以第三胎最高,各胎次P浓度差异极显著(p<0.01),第3胎与第1、2胎E2浓度差异显著(p<0.05).各胎次间FSH和T浓度差异不显著(p>0.05);胎次与六种激素以及各激素间的相关性均很小,胎次与孕酮(P)和促卵泡激素(FSH)呈负相关,FSH与LH、T和E2为负相关,LH与E2间的相关性具有显著性(p<0.05);六种激素与胎次回归方程的截距A和回归系数均不相同.     

Zoological origin of gonadotropin subunits and association kinetics

Mammalian luteinizing hormone (LH) is an association of two dissimilar subunits, alpha and beta. In vitro studies, mainly using difference spectrophotometry, had shown that this phenomenon was slow, especially at low temperatures. If the situation was the same in poikiloterms, it would probably make gonadotropin (GTH) synthesis difficult for these animals in a cold environment. We have found that the formation of a teleost gonadotropin is in fact strikingly more rapid and less thermodependent than formation of mammalian LH. Also, studies with a fish-mammal hybrid molecule have allowed us to estimate the respective influence of the alpha and beta subunits in determining these differences.     

FSH研究进展

卵泡刺激素（Follicle stimulating hormone,FSH）是由动物脑垂体前叶嗜碱性细胞合成与分泌的一种糖蛋白类促性腺激素,其在畜牧业以及医学等领域有着广阔的应用。FSH在畜牧业当中常应用于动物超数排卵、体外受精,并且FSHβ基因与动物产仔关系密切。在医学领域,FSH常用来治疗男女不孕不育等疾病,并且FSH与绝经期妇女骨密度（BMD）丢失以及女性卵巢癌等疾病也有很大的联系。文章简要概述FSH的生物学功能和机理,综述了其在畜牧业以及医学领域的研究与应用。     

Changes in hypothalamic preproenkephalin A mRNA following stress and opiate withdrawal

The median eminence of the pituitary is rich in opioid receptors, and exogenous opioids have major effects on the release of adrenocorticotropic hormone (ACTH), luteinizing hormone (LH), prolactin, growth hormone (GH) and thyrotropin. Stress results in similar changes in anterior pituitary hormone secretion. Enkephalin immunoreactivity has been reported in the medial parvocellular neurons of the hypothalamic paraventricular nucleus which project to the median eminence, the site where hypothalamic releasing factors are secreted into the portal blood and thence to the anterior pituitary gland. The endocrine response to stressful stimuli might therefore, at least in part, be mediated through the activation of hypothalamic enkephalinergic neurons. We show that two stressful stimuli, opiate withdrawal and intraperitoneal injection of hypertonic saline, both result in very rapid and marked increases in enkephalin mRNA in the parvocellular paraventricular nucleus. The activation of hypothalamic enkephalin neurons may be important in the neuroendocrine response to stress.     

Discrete cis-active genomic sequences dictate the pituitary cell type-specific expression of rat prolactin and growth hormone genes

The anterior pituitary gland, which is derived from a common primordium originating in Rathke's pouch, contains phenotypically distinct cell types, each of which express discrete trophic hormones: adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), prolactin, growth hormone, and follicle stimulating hormone (FSH)/luteinizing hormone (LH). The structurally related prolactin and growth hormone genes, which are evolutionarily derived from a single primordial gene, are expressed in discrete cell types--lactotrophs and somatotrophs, respectively--with their expression virtually limited to the pituitary gland. The pituitary hormones exhibit a temporal pattern of developmental expression with rat growth hormone and prolactin characteristically being the last hormones expressed. The reported co-expression of these two structurally related neuroendocrine genes within single cells prior to the appearance of mature lactotrophs, in a subpopulation of mature anterior pituitary cells, and in many pituitary adenomas raises the possibility that the prolactin and growth hormone genes are developmentally controlled by a common factor(s). We now report the identification and characterization of nucleotide sequences in the 5'-flanking regions of the rat prolactin and growth hormone genes, respectively, which act in a position- and orientation-independent fashion to transfer cell-specific expression to heterologous genes. At least one putative trans-acting factor required for the growth hormone genomic sequence to exert its effects is apparently different from those modulating the corresponding enhancer element(s) of the prolactin gene because a pituitary 'lactotroph' cell line producing prolactin but not growth hormone selectively fails to express fusion genes containing the growth hormone enhancer sequence.     

A prolactin-inhibiting factor within the precursor for human gonadotropin-releasing hormone

The cloned complementary DNA sequence encoding the human gonadotropin-releasing hormone (GnRH) precursor protein was used to construct an expression vector for the bacterial synthesis of the 56-amino acid GnRH-associated peptide (GAP). GAP was found to be a potent inhibitor of prolactin secretion and to stimulate the release of gonadotropins in rat pituitary cell cultures. Active immunization with peptides corresponding to GAP sequences led to greatly increased prolactin secretion in rabbits.