Transcriptional regulation of Sertoli cell differentiation (transferrin promoter activation) during testicular development.
Previously testicular peritubular cells have been shown to produce a paracrine factor PModS that promotes Sertoli cell differentiation. This mesenchymal-epithelial cell interaction appears to regulate a number of Sertoli cell differentiated functions including transferrin gene expression. The current study was designed to identify PModS-activated response elements in the transferrin promoter and correlate this with Sertoli cell differentiation that occurs during testis development. The 3-kb transferrin promoter was digested down to approximately 200-bp fragments. Nuclear extracts from Sertoli cells stimulated with PModS were used in gel mobility shift assays. Two promoter regions located at -2.4 kb and -1.9 kb were designated SE1 and SE2. PModS promoted the presence of factors in Sertoli cell nuclear extracts that bind SE1 and SE2. Displacement studies demonstrated that SE1 and SE2 are distinct. A transferrin promoter-reporter construct containing these apparent response elements was activated by PModS, while a minimal transferrin promoter by 600bp excluding SE1 and SE2 was only partially stimulated by PModS. Therefore, PModS appears to in part activate the transferrin promoter through SE1 and/or SE2. Gel shift assays with Sertoli cell nuclear extracts and 20-day-old testis extracts were the same. Interestingly, the nuclear extract from a newborn testis also had a gel shift. Therefore, some of the nuclear factors stimulated by PModS in Sertoli cells and present in mid-pubertal testis were also present at birth upon completion of embryonic development. Previously transferrin expression has been shown to increase significantly at the onset of puberty.(ABSTRACT TRUNCATED AT 250 WORDS)
Chaudhary
J
J
Reproductive Endocrinology Center, University of California, San Francisco 94143-0556, USA.
Skinner
M K
MK
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D005786:Gene Expression Regulation; D008297:Male; D011401:Promoter Regions, Genetic; D051381:Rats; D012708:Sertoli Cells / Q000166:cytology / Q000502:physiology*; D013737:Testis / Q000166:cytology / Q000254:growth & development*; D014158:Transcription, Genetic; D014168:Transferrin / Q000235:genetics*
D014168:Transferrin