Irradiation selectively inhibits expression from the androgen-dependent pem homeobox gene promoter in sertoli cells

How radiation blocks spermatogenesis in certain strains of rats. such as LB NF1, is not known. Because the block depends on androgen, we propose that a ndrogen affects Sertoli cell function in irradiated LBNF1 rats, resulting i n the failure of spermatogonial differentiation. To begin to identify genes that may participate in this irradiation-induced blockade of spermatogenes is, we investigated the expression of several Sertoli genes in response to irradiation. The expression of the Pem homeobox gene from its androgen-depe ndent Sertoli-specific proximal promoter (Pp) was dramatically reduced more than 100-fold in response to irradiation. In contrast, most other genes an d gene products reported to be localized to the Sertoli cell, including FSH receptor (FSHR), androgen receptor (AR), SGP1, and the transcription facto r CREB, did not exhibit significant changes in expression, whereas transfer rin messenger RNA (mRNA) expression dramatically increased in response to i rradiation. Irradiation also decreased Pp-driven Pen mRNA levels in mouse t estes (approximately 10-fold), although higher doses of irradiation than in rats were required to inhibit Pem gene expression in testes of mice, consi stent with their greater radioresistance. The decrease in Pem gene expressi on in mouse testis was also selective, as the expression of CREB, GATA-1, a nd SGP1 were little affected by irradiation. We conclude that the dramatic irradiation-triggered reduction of Pem expression in Sertoli cells is a con served response that may be a marker for functional changes in response to irradiation.