PITUITARY FOLLICLE-STIMULATING-HORMONE (FSH) INDUCES CREM GENE-EXPRESSION IN SERTOLI CELLS - INVOLVEMENT IN LONG-TERM DESENSITIZATION OF THE FSH RECEPTOR

Transcription factor CREM (cAMP-responsive element modulator) plays a pivotal role in the nuclear response to cAMP in neuroendocrine cells. We have previously shown that follicle-stimulating hormone (FSH) direc ts CREM expression in male germ cells. The physiological importance of FSH in Sertoli cell function prompted us to analyze its effect on CRE M expression in these cells. We observed a dramatic and specific incre ase in the CREM isoform ICER (inducible cAMP early repressor) expressi on, with a peak 4 h after FSH treatment of primary Sertoli cells. Inte restingly, induced levels of ICER protein persist for a considerably l onger time. Induction of the repressor ICER accompanies early down-reg ulation of the FSH receptor transcript, which leads to long-term desen sitization. Here we show that ICER represses FSH receptor expression b y binding to a CRE-like sequence in the regulatory region of the gene. Our results confirm the crucial role played by CREM in hormonal contr ol and suggest its role in the long-term desensitization phenomenon of peptide membrane receptors.