Mechanisms involved in the homologous down-regulation of transcription of the follicle-stimulating hormone receptor gene in Sertoli cells

The action of follicle-stimulating hormone (FSH) in spermatogenesis is regu lated at a fundamental level by controlling the number of competent recepto rs present at the surface of Sertoli cells. By controlling the number of re ceptors. the cell is able to modulate the timing and magnitude of subsequen t signal transduction in response to FSH. One mechanism of control is the d own-regulation of the steady state levels of the FSH receptor gene after ex posure to FSH or agents that stimulate or prolong the cAMP signal transduct ion cascade (homologous down-regulation) in Sertoli cells. The goals of thi s study were to examine possible mechanisms involved in the down-regulation of mRNA levels of this gene. Analysis of transcription and processing by a PCR-based assay showed that treatment of Sertoli cells with FSH caused at least a 50% reduction of hnRNA for the FSH receptor gene. Reporter genes co ntrolled by 5' flanking sequences of the FSH receptor gene that were transi ently transfected into Sertoli cells were not down-regulated. In electropho retic mobility shift assays (EMSA), cAMP-inducible nuclear protein complex containing c-Fos Formed on the activator protein-1/cAMP responsive element- like site located at - 216 to - 210 in the promoter of the rat FSH receptor gene. We concluded from this study that there was no evidence for the puta tive role of ICER in the down-regulation of the FSH receptor promoter. In a ddition, the FSH-induced down-regulation of the transcription of the FSH re ceptor gene in Sertoli cells was prevented by the treatment of Sertoli cell s with trichostatin A prior to the addition of FSH. This experiment coupled with other observations suggested that the down-regulation may be mediated by changes in chromatin structure. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.