The follicle stimulating hormone receptor (FSHR) is an essential G-protein-coupled receptor expressed in granulosa cells of the ovary and Sertoli cells of the testis. Upon hormone binding, the FSHR activates G-proteins, initiates gonadotropin signals and triggers granulosa cells and oocyte or Sertoli cells and germ cells communication that is required for gonadal development and maturation. This hormone signaling also participates in the biosynthesis of progesterone and estradiol in females and testosterone in males. The expression of FSHR reaches higher levels in mature follicles and in stages XIII-I of the seminiferous epithelial cycle. Little is known on the mechanisms by which cell- and stage-specific expression of FSHR is regulated. In the present studies, we have characterized four cis-elements in an ovine FSHR (oFSHR) promoter, and identified the corresponding DNA binding proteins. The first cis-element at +32 to +54 of the proximal oFSHR promoter was characterized as an E-box overlapping an orphan receptor response element (ORRE) to which upstream stimulatory factors (USFs) and chicken ovalbumin upstream promoter transcription factors (COUP-TFs) can compete for their binding. The second element was mapped at -46 to -67 as a CACC box that Krupple-like transcription factors recognize. The third cis-element at -117 to -197 was found to be a composite activator protein-1 (AP-1) binding site embedding an E-box and an ORRE that a group of proteins including AP-1, steroidogenic factor-1 (SF-1) and COUP-TFs can competitively occupy depending on their availability and activity. The fourth element from -284 to -303 was identified as a composite retinoic acid response element (RARE) that is recognized by retinoic acid receptors (RARs) and SF-1. Functional studies revealed that USFs, AP-1 and SF-1 were activators whereas COUP-TFs and RARs were repressors in the presence of retinoic acid (RA). Our data suggest a mechanism by which activators and repressors compete for
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.38439 |
| Date | January 2002 |
| Creators | Xing, Weirong, 1961- |
| Contributors | Sairam, M. R. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001864183, proquestno: NQ78800, Theses scanned by UMI/ProQuest. |
Page generated in 0.0115 seconds