Irradiation selectively inhibits expression from the androgen-dependent Pem homeobox gene promoter in Sertoli cells
Maiti,Sourindra; Meistrich,Marvin L.; Wilson,Gene; Shetty,Gunapala; Marcelli,Marco; McPhaul,Michael J.; Morris,Patricia L.; Wilkinson,Miles F.
Endocrinology 142(4): 1567-1577
Publication date: 2001
How radiation blocks spermatogenesis in certain strains of rats,such as LBNF, is not known. Because the block depends on androgen,we propose that androgen affects Sertoli cell function in irradiatedLBNF rats, resulting in the failure of spermatogonial differentiation.To begin to identify genes that may participate in this irradiation-inducedblockade of spermatogenesis, we investigated the expressionof several Sertoli genes in response to irradiation. The expressionof the Pem homeobox gene from its androgen-dependent Sertoli-specificproximal promoter (Pp) was dramatically reduced more than 100-foldin response to irradiation. In contrast, most other genes andgene products reported to be localized to the Sertoli cell,including FSH receptor (FSHR), androgen receptor (AR), SGP1,and the transcription factor CREB, did not exhibit significantchanges in expression, whereas transferrin messenger RNA (mRNA)expression dramatically increased in response to irradiation. Irradiationalso decreased Pp-driven Pem mRNA levels in mouse testes (approximately10-fold), although higher doses of irradiation than in ratswere required to inhibit Pem gene expression in testes of mice,consistent with their greater radioresistance. The decreasein Pem gene expression in mouse testis was also selective, asthe expression of CREB, GATA-1, and SGP1 were little affectedby irradiation. We conclude that the dramatic irradiation-triggeredreduction of Pem expression in Sertoli cells is a conservedresponse that may be a marker for functional changes in responseto irradiation.