Gonadal Receptors/Mechanisms Of Action Of Hormones

黄体生成素受体：黄体生成素受体(LRH)是一种无TATA的基因，其转录由Sp1/Sp3驱动。对孤儿受体介导的黄体生成素受体转录沉默机制的功能研究已经建立了与DNA直接重复序列结合的孤儿受体EAR3/Coup-TFI和Sp1/SP3复合体之间的功能联系。EAR3通过TFIIB干扰Sp1位点的Sp1/Sp3和基础转录复合体之间的通讯，减少RNA Pol II的募集。这一机制被发现在卵巢周期LHR的抑制/诱导状态下起作用。 睾丸功能调控：本研究克隆的促性腺激素调节的睾丸RNA解旋酶(Grth/Ddx25)是DEAD-box家族的新成员。这种睾丸特异的酶存在于间质细胞和生殖细胞(粗线期精母细胞、圆形精子细胞)中，是第一个被发现受激素(促性腺激素/雄激素)调节的成员。最近的研究已经确定了三个翻译起始密码子，它们用于产生多个物种。这些研究已经证明了ATG密码子在大鼠睾丸中的一种细胞特异性和雄激素依赖性的替代使用。睾丸间质细胞中睾酮的自分泌作用和小管部位(圆形精子细胞)的旁分泌作用在转录水平上引起Grth的增加，并在翻译水平上促进第二个ATG密码子在两种细胞中的利用。 催乳素受体：催乳素通过其同源受体(hPRLR-long form)作用，激活JAK2/Stat5途径，这是催乳素诱导乳腺上皮分化所必需的。人们普遍认为，催乳素诱导的同源二聚化是激活后续信号通路所必需的。然而，目前的研究表明，长形式受体的同源二聚化可以独立于催乳素。他们还证明了hPRLR的长形式(激活)和在分支中发现的两种短形式(显性阻遏形式)之间的异二聚体，表明同源二聚体和异源二聚体是结构性存在的。激素刺激可以作用于预先形成的长形式同源二聚体，通过引起细胞质结构域的构象变化来诱导信号转导。任何一种短形式的异二聚化都可以消除激素诱导的结构变化，这些变化是激活二聚体长形式受体所必需的。

The LH receptor: The luteinizing hormone receptor (LRH) is a TATAless gene whose transcription is driven by Sp1/Sp3. Functional studies on the mechanism of orphan receptor-mediated silencing of transcription of the luteinizing hormone receptor have established a functional connection between the orphan receptor EAR3/COUP-TFI bound to a DNA direct repeat and the Sp1/Sp3 complex. EAR3 perturbs the communication between Sp1/Sp3 at the Sp1 site and the basal transcription complex through TFIIB, and reduces recruitment of RNA Pol II. This mechanism has been found to be operative in repressive/inductive states of the LHR during the ovarian cycle. Control of testicular function:The gonadotropin-regulated testicular RNA helicase (GRTH/Ddx25) cloned in this Branch is novel member of the DEAD-box family. This testis-specific enzyme is present in Leydig and germ cells (pachytene spermatocytes, round spermatids), and is the first member found to be regulated by hormones (gonadotropin/androgen). Recent studies have identified three translation initiation codons that are utilized for the generation of multiple species. The studies have demonstrated a cell-specific and androgen-dependent alternative usage of ATG codons in the rat testis. The autocrine actions of testosterone in Leydig cells and paracrine actions at tubule sites (round spermatids) cause increases of GRTH at the transcriptional level and promote the utilization of the 2nd ATG codon in both cell types at the translational level. The Prolactin receptor: Acting through its cognate receptor (hPRLR-long form), prolactin activates Jak2/Stat5 pathway, which is essential for prolactin-induced differentiation of mammary epithelium. It was generally accepted that prolactin-induced homodimerization is required for the activation of subsequent signalling pathways. However,current studies demonstrated that homodimerization of the long form of the receptor can be independent of prolactin. They also demonstrated heterodimerization between the long form of the hPRLR (activating) and either of the two short forms discovered in the branch (dominant repressor forms), indicating that homodimers and heterodimers are constitutively present. The hormonal stimulus could act on the preformed homodimer of the long form to induce the signaling by causing changes in conformation of the cytoplasmic domain. Heterodimerization with either short form could abrogate the hormone-induced structural changes that are required for activation of the dimeric long form of the receptor.