GONADAL RECEPTORS/MECHANISMS OF ACTION OF PEPTIDE HORMONES IN STEROIDOGENIC CELL

1)黄体生成素受体：人/大鼠黄体生成素受体(LHR)TATAless基因的176个启动子区域包含两个对转录具有重要作用的Sp1/Sp3结合域。在人类基因中，位于Sp1启动子5‘端的雌激素受体半重复反应元件直接重复序列(D0)被鉴定为Sp1/Sp3调控转录的抑制位点。二聚体核受体EAR2、EAR3/COUP-TF1和TR4(核提取物、大鼠、人睾丸或体外翻译)与LHR启动子的直接重复序列结合。对CV1细胞(没有孤儿)的功能分析表明，EAR2和EAR3抑制转录，而TR4通过结合相同的顺式元件刺激转录活动。这种刺激被EAR2或EAR3的共表达逆转，表明竞争该位点。具有拮抗功能的蛋白质对共同位点的识别意味着hLHR基因的网络/调节/和/或表达可能是由于抑制物和激活物在器官和生理状态下的相对可用性。这也可能是导致LHR基因在性腺和非性腺组织中表达差异的原因之一。2)促性腺激素调节：从大鼠、小鼠和人睾丸中克隆的促性腺激素调节的睾丸RNA解旋酶(Grth)是DEAD-box蛋白家族的新成员。GTRH显示ATPase和RNA解旋酶活性，并刺激RNA模板的翻译。该解旋酶在大鼠、小鼠和人的睾丸中高度表达，在垂体和下丘脑中表达较弱。Grth在间质细胞和减数分裂细胞中的表达受发育调控。HCG通过cAMP诱导间质细胞中雄激素的形成，在转录水平上上调Grth。这种新的解旋酶可能与类固醇合成的调控和雄激素依赖的精子发生的旁分泌调节有关。3)瘦素在间质细胞功能中的作用：大鼠间质细胞表达瘦素的两种亚型。瘦素引起hCG刺激的睾酮产生的急性抑制。伴随着雄烯二酮的显著减少和近端类固醇前体的增加，表明瘦素诱导的17，20裂解酶活性的损害。这一结果对男性生殖的一些临床方面有一定的影响，例如肥胖男性的睾丸功能下降。

1) The LH receptor: The 176 bp human/rat promoter domain of the LH receptor (LHR) TATAless gene contains two Sp1/Sp3 binding domains of central importance for transcription. An imperfect estrogen receptor half-site response element direct-repeat (D0), located within the promoter 5'to the Sp1 sites, was identified in the human gene as an inhibitory site for the Sp1/Sp3 driven transcription. Dimeric nuclear receptors EAR2, EAR3/COUP-TF1 and TR4 (nuclear extracts, rat, human testis or in vitro translated) bound the direct-repeat of the LHR promoter. Functional analyses in CV1 cells (devoid of orphans) demonstrated that EAR2 and EAR3 repress and TR4 stimulates transcriptional activity through binding the same cis-element. The stimulation was reversed by coexpression of EAR2 or EAR3 indicating competition for this site. Such recognition of a common site by proteins with antagonist functions implies that the net/regulation/ and or expression of the hLHR gene may result from the relative availability of repressor and activator in the organ and physiological state. This may also contribute to the differential expression of the LHR gene in gonadal and non-gonadal tissues. 2) Gonadotropin regulation: A novel gonadotropin-regulated testicular RNA helicase (GRTH) cloned from rat Leydig cell, mouse and human testis cDNA libraries is a novel member of the DEAD-box protein family. GTRH displayed ATPase and RNA helicase activities and stimulated translation of RNA templates. This helicase is highly expressed in rat, mouse and human testes and weakly in the pituitary and hypothalamus. GRTH expressed in Leydig and meiotic cells is developmentally regulated. GRTH is transcriptionally up-regulated by hCG via cAMP-induced androgen formation in the Leydig cell. This novel helicase could be relevant to the control of steroidogenesis and the paracrine regulation of androgen- dependent spermatogenesis in the testis. 3) Leptin in Leydig cell function: Rat Leydig cells express both isoforms of leptin. Leptin cause an acute inhibition of hCG stimulated testosterone production. This was accompanied by a significant reduction of androstenedione and a rise of proximal steroid precursors indicating a leptin-induced lesion of 17,20 lyase activity. The results have implications in some clinical aspects of male reproduction, such as the reduced testicular function in obese males.