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

1) LH受体：LH受体（LHR） TATAless基因的176 bp人/大鼠启动子结构域包含两个对转录至关重要的Sp1/Sp3结合结构域。一个不完善的雌激素受体半位点反应元件直接重复（D0），位于Sp1位点的启动子5'中，在人类基因中被鉴定为Sp1/Sp3驱动转录的抑制位点。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）结合LHR启动子的直接重复序列。在CV1细胞（不含孤儿）中的功能分析表明，EAR2和EAR3通过结合相同的顺式元件抑制转录活性，而TR4通过结合相同的顺式元件刺激转录活性。刺激被EAR2或EAR3的共表达逆转，表明该位点存在竞争。具有拮抗剂功能的蛋白质对共同位点的识别表明，hLHR基因的net/调控和/或表达可能是由器官和生理状态中抑制因子和激活因子的相对可用性引起的。这也可能导致LHR基因在性腺和非性腺组织中的差异表达。2)促性腺激素调节：从大鼠睾丸间质细胞、小鼠和人睾丸cDNA文库中克隆的促性腺激素调节睾丸RNA解旋酶（GRTH）是DEAD-box蛋白家族的新成员。GTRH显示atp酶和RNA解旋酶活性，并刺激RNA模板的翻译。该解旋酶在大鼠、小鼠和人睾丸中高表达，在垂体和下丘脑中低表达。在间质细胞和减数分裂细胞中表达的GRTH受发育调控。通过camp诱导的间质细胞雄激素形成，hCG上调了GRTH的转录水平。这种新的解旋酶可能与睾丸激素生成的控制和雄激素依赖性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。这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裂解酶活性损伤。该结果对男性生殖的一些临床方面有启示，如肥胖男性睾丸功能降低。

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.