DIFFERENTIAL ANDROGEN REGULATION OF THE MURINE GENES FOR CYSTEINE-RICH SECRETORY PROTEINS (CRISP)

The androgen dependency of the genes coding for the cysteine-rich secr etory proteins (CRISP) was analysed in their main sites of expression. Male mice were treated with the gonadotropin-releasing hormone antago nist Ala-DPyrAla-Ser-Tyr-DCtl-Leu-Lys(Mor)-Pro-DAla-NH2 [DNapAla, D-2- naphthyl-Ala; DClPhAla, D-4-chlorphenyl-Ala; DPyrAla, D-pyridyn-3-yl-A la; DCtl, D-citrulline; Lys(Mor), L-2-amino-6-(morpholin-4-yl)-hexanoi c acid], and CRISP RNA levels were assessed by northern blot and compe titive reverse transcriptase-mediated (RT)-PCR. In the salivary gland, CRISP-I and to a lesser extent CRISP-3 expression was markedly reduce d, in spite of an up-regulation of androgen receptor transcript levels . A down-regulation of CRISP-I expression was also observed in the epi didymis. Conversely, the levels of the testicular CRISP-2 transcripts were hardly affected at all. Female mice were ovariectomised and treat ed with testosterone propionate, and their salivary gland RNAs analyse d. CRISP-I and CRISP-3 RNA levels were significantly increased, and th ese effects were prevented by a concomitant treatment with the antiand rogen flutamide. Androgen receptor transcript levels were not affected by androgen administration but increased following antiandrogen treat ment. CRISP expression during postnatal development was monitored by n orthern blot analysis. CRISP-I and CRISP-2 transcripts were detected a s early as 22 days after birth in the epididymis and testis, respectiv ely, whereas CRISP-3 mRNA was visible only from day 30 in the salivary gland. A sharp increase of all CRISP levels was noted on day 40, coin cident with the onset of sexual maturity. Altogether these results ind icate that despite their high similarity, the CRISP genes are differen tially regulated by androgens.