1) The LH receptor: The luteinizing hormone receptor (LHR) is an essential component in the control of gonadal function. The promoter domain of the human LHR gene has been identified within the 5 176bp region (from ATG). The major transcriptional sites (TSS) are located within the 176 bp promoter of this TATAless gene in gonadal and non-gonadal tissues. Upstream TSS were identified in the human testis (- 1087 bp) and choriocarcinoma cells (-245 to 463 bp). In the rat, the LHR gene appears to be constitutively inhibited by upstream sequences (-176 to 2056 bp) in several in vitro systems (stable and primary cell cultures). However, in the human there is cell- type specific upstream inhibition. The differences between rodent and human may be related to the presence of cell-specific transcriptional factor(s) and or due to differences in the 5 flanking of the LHR gene (60% similarity). The participation of an upstream promoter in human cells cannot be excluded, which also may explain the over-expression of LHR mRNA in JAR tumor cells (choriocarcinoma) vs. normal placental cells. The 176 bp promoter contains two Sp1 domains of central importance which interact with endogenous Sp1 and Sp3 factors. An imperfect estrogen receptor half-site response element direct-repeat, located within the promoter 5 to the Sp1 sites, was identified as the inhibitory site for Sp1/Sp3-driven basal transcription. Mutation of this site causes a 100% increase in basal promoter activity. This regulatory site may contribute to the differential regulation of expression of the gene in gonadal and non-gonadal tissues. 2) Prolactin receptor: The structure of the human prolactin receptor (hPRLR) gene has been resolved. The 5-untranslated region contains 6 alternative first exons: hE1-3, the human homolog of the rat/mouse, and hE1-N1-5, human-specific. It also contains one common non- coding exon 2. The coding region comprises exons 3-10. The differential promoter utilization of the hPRLR gene in diverse tissues may confer individual prolactin responses through activation of different promoters. 3) Hormonal Control of Steroidogenesis: 17-b steroid dehydrogenase type 3 (17b-HSD) is a Leydig cell enzyme that generates testosterone from androstenedione. Our studies have demonstrated that the enzyme activity is dependent on cell glucose through ATP generation. The rat enzyme isoform 3 was cloned. This enzyme is down- regulated by gonadotropin at the transcriptional level. The enzyme activity in transfected cells was markedly reduced in the absence of glucose. These studies provide a basis for elucidation of the regulatory mechanism(s) of 17b-HSD activity.
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