Relaxin affects the central control of oxytocin release

In several species the myometrium is quiescent shortly before parturition. At this time high titres of relaxin are present in the plasma and there is evidence that the hormone has a direct inhibitory action on the uterine muscle. Relaxin could also contribute to uterine quiescence by inhibiting oxytocin release. To determine whether relaxin has a central action on the release of oxytocin, we have studied the effect of intravenous injections of porcine relaxin on milk ejection in the anaesthetized lactating rat. We report that reflex milk ejection was suppressed by relaxin in a dose-dependent manner, the onset of inhibition being rapid and lasting from 10 to 60 min. After the period of inhibition the normal temporal pattern of reflex milk ejection was resumed. Mammary sensitivity to exogenous or endogenous oxytocin was reduced by relaxin but not sufficiently to explain the effects observed. Furthermore, relaxin (1 microgram per rat) injected into the cerebral ventricles profoundly disturbed the pattern of reflex milk ejection without affecting the response of the mammary gland to oxytocin. These results suggest a novel role for relaxin within the central nervous system. The site in the brain at which the effects of relaxin are exerted remains unknown.     

Effect of UPP on the expression of VEGF and its receptors in mouse uterus during peri-implantation

On day 3 of gestation ,one uterine horn of female pregnant mouse was injected intraluminally with 5 μL 0.1μg/mL lactacystin,a specific inhibitor of ubiquitin-pro-teasome pathway (UPP),while the contralateral horn served as control ,Animals were sacrificed by cervical dislocation on day 5,6,7 of gestation ,respectively,Then the number of implanted embryos in each uterine horn was calcuated,and the expression of VEGF and its receptors was examined,The data showed that the number of implanted embryos was decreased significantly after treatment with lactacystin ,The results of RT-PCR and Western blot indicated that expression of VEGF and its receptors at mRNA and protein levels was significantly decreased in the treated uterus,menawhile,the expression of HIF-1α(the α subunit of HIF ,a transcrip-tional factor of VEGF) was reduced at both mRNA and protein levels,These data suggested that the effect of UPP on VEGF expression was realized through regulating HIF-1α expression .In addition ,UPP is likely to take part in the modulation of VEGF receptors expression ,These changes may be one of the reasons for the reduction of implanted embryos.     

云南松松塔正丁醇提取物对大鼠离体子 宫平滑肌的影响

目的研究云南松松塔正丁醇提取物对大鼠离体子宫平滑肌的作用。方法通过制备大鼠离体子宫标本,观察云南松松塔正丁醇提取物对大鼠离体子宫平滑肌自发收缩活动,催产素及乙酰胆碱诱发收缩活动的影响。结果云南松松塔正丁醇提取物可使正常大鼠自发收缩和催产素及乙酰胆碱诱发收缩的频率减慢、张力减小、活动力减弱。结论云南松松塔正丁醇提取物对大鼠离体子宫平滑肌的收缩活动具有抑制作用,其机制可能跟阻断催产素受体和M受体有关。     

Apparent role of the macrophage growth factor, CSF-1, in placental development

Colony stimulating factor-1 (CSF-1) is a glycoprotein growth factor required for the proliferation and differentiation of mononuclear phagocytic cells (reviewed in ref. 1). A 10,000-fold elevation of mouse uterine CSF-1 during pregnancy, suggested by studies of the bone marrow colony stimulating activity of uterine extracts, was recently demonstrated by radioimmunoassay (RIA). This increase and the observations that placenta and choriocarcinoma cell lines express c-fms messenger RNA and the c-fms proto oncogene product (CSF-1 receptor) respectively, suggest an additional role for CSF-1 in pregnancy. We now show that uterine CSF-1 concentration is regulated by the synergistic action of female sex steroids, oestradiol-17 beta (E2) and progesterone (P) and that the elevation in CSF-1 concentration can be attributed to the preferential expression of an alternatively spliced CSF-1 mRNA by uterine glandular epithelial cells. These findings indicate that CSF-1, under hormonal influence, plays a role in placental development and function and that steroid hormones may regulate developmental processes via their effects on the expression of tissue-specific growth factors.     

Relaxin affects the release of oxytocin and vasopressin from the neurohypophysis

The hormone relaxin has recently been shown to inhibit not only uterine muscle contraction, but also the release of oxytocin into the plasma. Intravenous injection of porcine relaxin in anaesthetized lactating rats inhibits milk ejection and injection of relaxin into the cerebral ventricles disturbs the pattern of the milk ejection reflex. Recent experiments performed in vivo indicate that relaxin might act not only in the uterus, but also in the hypothalamus and possibly in the neurohypophysis. We tested this hypothesis in vitro by studying the effect of relaxin on hormone release from isolated neural lobes of the pituitary and isolated neurosecretory nerve endings of the neurohypophysis from the rat. We report here that relaxin has a dual effect on neurohypophysial hormone secretion. Under basal conditions, vasopressin and oxytocin release was inhibited by relaxin but, when the nerve endings were depolarized, vasopressin and oxytocin secretion was potentiated. We also found that relaxin acts at a stage before the increase in cytoplasmic free Ca2+ that is necessary for inducing hormone release, possibly by gating the calcium channel.     

Equilibrium: the intracellular distribution of steroid receptors

Data are presented which suggest that there are unbound receptors for oestrogen in nuclei of the smooth muscle cells of the myometrium. A new model for the distribution of unbound receptors is proposed in which unbound receptor is in equilibrium, partitioned between nucleus and cytoplasm according to the free water content of these intracellular compartments.     

Spatial and temporal expression of the retinoic acid receptor in the regenerating amphibian limb

Retinoic acid is known to have dramatic effects on vertebrate limb pattern in development and regeneration, supporting a model in which a gradient of retinoic acid serves as a morphogen to differentially supply positional information to a developing limb. The discovery of a retinoic acid receptor (RAR) and its homology to the steroid and thyroid hormone receptors provided a potential molecular mechanism for limb morphogenesis. One prediction of this model is that the receptor must be expressed in the developing and regenerating limb anlage. We investigated the expression of the RAR in the adult newt, Notophthalmus viridescens, whose amputated limbs are capable of regenerating and upon which retinoic acid can act to alter pattern. We report the cloning of cDNAs encoding a functional newt RAR and the localization of high and uniform levels of RAR mRNA specifically in the regenerating cells that control limb pattern. These results indicate that the morphogenic field is established through differential activation of pre-existing retinoic acid receptors rather than differential expression of the RAR gene.     

Regulation of AMPA receptor lateral movements

An essential feature in the modulation of the efficacy of synaptic transmission is rapid changes in the number of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors at post-synaptic sites on neurons. Regulation of receptor endo- and exocytosis has been shown to be involved in this process. Whether regulated lateral diffusion of receptors in the plasma membrane also participates in receptor exchange to and from post-synaptic sites remains unknown. We analysed the lateral mobility of native AMPA receptors containing the glutamate receptor subunit GluR2 in rat cultured hippocampal neurons, using single-particle tracking and video microscopy. Here we show that AMPA receptors alternate within seconds between rapid diffusive and stationary behaviour. During maturation of neurons, stationary periods increase in frequency and length, often in spatial correlation with synaptic sites. Raising intracellular calcium, a central element in synaptic plasticity, triggers rapid receptor immobilization and local accumulation on the neuronal surface. We suggest that calcium influx prevents AMPA receptors from diffusing, and that lateral receptor diffusion to and from synaptic sites acts in the rapid and controlled regulation of receptor numbers at synapses.     

Developmental regulation of T-cell receptor gene expression

In contrast to B cells or their antibody products, T lymphocytes have a dual specificity, for both the eliciting foreign antigen and for polymorphic determinants on cell surface glycoproteins encoded in the major histocompatibility complex (MHC restriction). The recent identification of T-cell receptor glycoproteins as well as the genes encoding T-cell receptor subunits will help to elucidate whether MHC proteins and foreign antigens are recognized by two T-cell receptors or by a single receptor. An important feature of MHC restriction is that it appears to be largely acquired by a differentiating T-cell population under the influence of MHC antigens expressed in the thymus, suggesting that precursor T cells are selected on the basis of their reactivity with MHC determinants expressed in the host thymus. To understand this process of 'thymus education', knowledge of the developmental regulation of T-cell receptor gene expression is necessary. Here we report that whereas messenger RNAs encoding the beta-and gamma-subunits are relatively abundant in immature thymocytes, alpha mRNA levels are very low. Interestingly, whereas alpha mRNA levels increase during further development and beta mRNA levels stay roughly constant, gamma mRNA falls to very low levels in mature T cells, suggesting a role for the gamma gene in T-cell differentiation.     

成年雄性斑胸草雀脑多巴胺D1受体的分布

多巴胺是脑内关键的神经递质,它通过与多巴胺受体的作用及其下游的一系列反应来影响基因表达、神经调节和行为活动.在成年鸣禽中,中脑多巴胺能神经元投射到X区、HVC和RA等鸣唱相关核团,释放多巴胺的量受一定社会情境的影响,从而表现出directed song和undirected song等不同鸣唱行为.获得斑胸草雀脑中多巴胺受体的表达情况,为与社会情境有关的鸣唱行为及其他和多巴胺相关的行为活动的神经机制探究提供了基础,并可促进行为学、电生理等方面的研究.我们发现D1受体在斑胸草雀脑中的分布与其mRNA的分布基本一致:在脑的绝大部分区域都有分布;主要鸣唱核团HVC和RA有表达,与其周围区域差异不明显;LMAN中表达量较少;DLM中的表达量较高,并与其周围区域差异明显.但是纹状体内的表达与其周围区域的差异性没有mRNA明显;GCT中的表达量较多,与周围区域差异明显.     

Evidence for opiate receptors on pituicytes

A hypothalamo-neurohypophyseal enkephalinergic pathway has been described and the pars nervosa of the rat pituitary contains enkephalin-like material which may coexist in vasopressin and oxytocin terminals. At the level of the pars nervosa itself, stereospecific opiate receptors with properties very similar to those of brain receptors have been described, and opiates have been shown to inhibit the release of both vasopressin and oxytocin. The location of the opiate receptors involved has been presumed to be pre-terminal on the neurosecretory fibres. Using an autoradiographic technique to visualize opiate receptors, however, we now report that destruction of the neurosecretory fibres following pituitary stalk section does not result in a significant change in the neural lobe opiate receptor population. This suggests that the opiate receptors within the neural lobe may be present on pituicytes rather than on neurosecretory fibres.     

Human cytomegalovirus encodes three G protein-coupled receptor homologues

Human cytomegalovirus (HCMV) is a herpesvirus with a genome of 230 kilobases (Kb) encoding about 200 genes. Although infection is generally innocuous, HCMV causes serious congenital and neonatal disease, and is a dangerous opportunistic pathogen in immune-deficient individuals. We have identified a family of three HCMV genes which encode polypeptides containing seven putative membrane-spanning domains, and a series of well-defined motifs characteristic of the rhodopsin-like G protein-coupled receptors (GCRs). By these criteria all three of the HCMV sequences are homologous to cellular GCRs. Members of this receptor family function in visual signal transduction, regulation of homeostasis, and development, and include known and potential oncogenes. These receptors are activated by photons or small molecules such as neurotransmitters, and glycoprotein hormones. The finding of viral-encoded GCR homologues implies a further level of complexity in the interactions between HCMV and its host, and may provide a potential pathway for virally transformed cell proliferation. Their identification could permit the development of a novel class of antiviral drugs analogous to beta-adrenergic receptor antagonists.     

Molecular cloning and expression of the gene for a human D1 dopamine receptor

The diverse physiological actions of dopamine are mediated by its interaction with two basic types of G protein-coupled receptor, D1 and D2, which stimulate and inhibit, respectively, the enzyme adenylyl cyclase. Alterations in the number or activity of these receptors may be a contributory factor in diseases such as Parkinson's disease and schizophrenia. Here we describe the isolation and characterization of the gene encoding a human D1 dopamine receptor. The coding region of this gene is intronless, unlike the gene encoding the D2 dopamine receptor. The D1 receptor gene encodes a protein of 446 amino acids having a predicted relative molecular mass of 49,300 and a transmembrane topology similar to that of other G protein-coupled receptors. Transient or stable expression of the cloned gene in host cells established specific ligand binding and functional activity characteristic of a D1 dopamine receptor coupled to stimulation of adenylyl cyclase. Northern blot analysis and in situ hybridization revealed that the messenger RNA for this receptor is most abundant in caudate, nucleus accumbens and olfactory tubercle, with little or no mRNA detectable in substantia nigra, liver, kidney, or heart. Several observations from this work in conjunction with results from other studies are consistent with the idea that other D1 dopamine receptor subtypes may exist.     

肥大细胞在人正常子宫的分布规律

目的：探讨肥大细胞(mast cell,MC)在人正常子宫内膜和肌层中的变化规律。方法：采用免疫组织化学和图象分析系统,对11例增生期、10例分泌期、9例绝经期子宫组织切片的MC进行测定。结果：人子宫内膜的MC数在增生期和分泌中晚期中明显增多,在分泌早期减少,在绝经期中显著减少。在肌层则未见MC数有周期性改变。结论：MC在子宫内膜呈周期性变化,分泌早期MC数量减少,将有利于胚泡的着床,绝经期MC数量的显著减少,提示其可能与绝经期妇女易患妇科恶性肿瘤相关。     

Interleukins 4 and 5 control expression of IL-2 receptor on murine B cells through independent induction of its two chains

Resting B cells express few, if any, receptors for interleukin-2 (IL-2), whereas activated B cells can express receptors for and respond to IL-2. IL-2 receptors can exist on the cell surface in three different forms; the complete high-affinity receptor, a heterodimer consisting of a chain of relative molecular mass (Mr) 70-75,000 (70-75K) and a chain of Mr 55K; the 70-75K chain alone, with intermediate affinity for IL-2; or the 55K chain alone, with low affinity for IL-2. We have previously reported that IL-5-stimulated B cells are induced to express the 55K chain. We report here evidence for the differential regulation of the expression of the two chains, namely that IL-4 and IL-5 can independently induce expression of the 70-75K and 55K chains respectively on murine B cells. As expected, cells stimulated to express the 55K chain alone are unresponsive to IL-2, whereas cells stimulated to express either the 70-75K chain or the 70-75/55K heterodimer respond to IL-2, at a high and low ligand concentration respectively, with a marked increase in proliferation. This orchestration of receptor expression and factor responsiveness may represent a novel activation pathway for B cells, where the two chains of a compound receptor are shown to be independently regulated.     

The scid mutation in mice causes a general defect in DNA repair

Mice homozygous for the scid mutation on chromosome 16 have a severe combined immune deficiency as a result of their inability to correctly rearrange their immunoglobulin and T-cell receptor genes. In scid mice, when precursors for B and T lymphocytes reach the stage of development requiring expression of these surface receptors, a defective recombinase system aberrantly cuts and rejoins the receptor gene segments greatly reducing the efficiency of producing functional receptors. As a result, most scid mice have no detectable B or T lymphocytes. We have demonstrated that the scid defect is not specific to lymphocyte development. Myeloid cells and fibroblasts from scid mice show a marked increase in sensitivity to ionizing radiation, indicating that the scid mutation leads to an inability to repair DNA damage induced by ionizing radiation as well as interfering with rearrangement of the immunoglobulin and T-cell receptor genes.