INCREASED EPIDERMAL GROWTH-FACTOR EXPRESSION PRODUCED BY TESTOSTERONEIN THE SUBMAXILLARY-GLAND OF FEMALE MICE IS ACCOMPANIED BY CHANGES INPOLY-A TAIL LENGTH AND PERIODICITY

The level of mature EGF messenger RNA (mRNA) in the female submaxillar y salivary gland (SMG) begins to rise after 3 days' treatment with tes tosterone (200 mu g sc qod), and by 5 days it reaches a plateau of app roximately 5 times baseline. Testosterone can increase the transcripti on of other genes in the SMG rapidly, so the lag in the EGF is not due to a slow androgen receptor response, and EGF mRNA can respond rapidl y to other mediators, so the lag is not an innate characteristic of EG F transcription. Immunoreactive EGF levels reach a steady-state severa l times greater than the plateau reached by EGF mRNA, suggesting that testosterone also enhances the efficiency of EGF mRNA translation. Bec ause testosterone has been reported to alter poly-A polymerase activit ies and because the translation and stability of some mRNAs is affecte d by changes in their polyadenylation, we used 3' rapid amplification of complementary DNA ends (3' RACE) to determine whether testosterone affected this aspect of EGF RNA metabolism. We found that EGF transcri pts in untreated female SMG occur in distinct size classes, with poly- A tails of approximately 20, 50, 70, 100, and 200 A's attached after t he terminal polyadenylation signal. In contrast, EGF transcripts in ma le SMG have poly-A tails of less clearly defined lengths, being more h eterogeneous, ranging from approximately 20-100 As. Treating female mi ce with testosterone causes the poly-A pattern in the SMG to change to a more heterogeneous population ranging from approximately 20-100 As, similar to the male pattern. This change in EGF transcript polyadenyl ation occurs concurrently with the changes observed in the levels of E GF mRNA. EGF transcripts from male or female kidney contain distinct p oly-A tails of approximately 20, 50, 70, 100, and 200 As: neither EGF mRNA levels nor polyadenylation was altered by testosterone. The tissu e-specific increase in EGF mRNA levels and in translational efficiency produced by testosterone in the female mouse SMG could involve this p osttranscriptional alteration in transcript polyadenylation.