THE CYTOSOLIC 47-KILODALTON PROTEIN THAT BINDS TO THE 3'-UNTRANSLATEDREGION OF EPIDERMAL GROWTH-FACTOR TRANSCRIPTS RESPONDS TO ORCHIECTOMYIN A TISSUE-SPECIFIC FASHION

The submaxillary gland (SMG) of the male mouse is known to contain mor e epidermal growth factor (EGF) messenger RNA (mRNA) than that of the female. In contrast, the SMG of female mice contains more of a cytosol ic 47-kDa RNA binding protein that binds to a unique 23-b sequence at the end of the 3' untranslated region (3' UTR) of EGF, which includes the canonical polyadenylation signal in an AU-rich region containing a potential mRNA destabilizing sequence. Testosterone treatment can cha nge the activity of this 47-kDa protein within 1 day, which precedes t he change produced in the level and in the polyadenylation of EGF mRNA in female mice. In the kidney, however, neither the 47-kDa protein no r the polyadenylation pattern changed after testosterone. We now repor t that 2 weeks following orchiectomy of Balb/c mice, mature EGF peptid e immunoreactivity levels fall by 96% (P < 0.0002), and mRNA levels fa ll by 76% (P < 0.0001). Orchiectomy also enhances the RNA binding acti vities of the 47-kDa protein in SMG cytosol but not in the kidney: UV cross-linking to 3' UTR RNA is increased by 67% (P < 0.01) and shiftin g of the gel mobility of the RNA is increased by 47% (P < 0.05). The p alyadenylation pattern of EGF transcripts also changes in SMG but not in kidney cytosol. After orchiectomy, the population of EGF transcript s in the SMG with short, heterogenous poly-A tails (<50 A's) decreases by 31% (P < 0.03), whereas transcripts with long poly-A tails of appr oximately 50, 70, 100, and 200 A's all increase and become more distin ct, resembling the pattern found in the normal female. Thus, 2 weeks a fter orchiectomy, the responses in EGF expression, EGF mRNA polyadenyl ation, and the activities of the 47-kDa 3' UTR binding protein are the reciprocal of the responses produced by injecting female mice with te stosterone for 5 days, providing further evidence that circulating and rogens regulate EGF expression posttranscriptionally in a sexually dim orphic, tissue-specific fashion.