Three different promoters control expression of the aromatase cytochrome P450 gene (Cyp19) in mouse gonads and brain

Abstract

Aromatase cytochrome P450, the key enzyme of estrogen biosynthesis, is encoded by Cyp19. To elucidate the complex regulation of this gene in mouse gonads (ovary and testis) and brain (thalamic/hypothalamic areas), Cyp19 transcripts were isolated using rapid amplification of cDNA 5′ ends and transcript concentrations were estimated in juveniles at different postnatal days (P0, P7, and P14) and in adult animals by real time polymerase chain reaction (PCR). In addition, the murine Cyp19 locus including all known exons and promoters was reconstructed from a recently published sequence of a mouse bacterial artificial chromosome. From each of the tissues investigated, Cyp19 transcripts with a specific 5′ untranslated region (5′ UTR) were isolated: Tov from ovary, Tbr from brain, and Ttes from testis. Ttes included a novel 5′ UTR that did not show sequence similarities to other Cyp19 transcripts. Real time PCR experiments revealed similar levels of Cyp19 transcript concentrations in neonatal gonads of both sexes. The majority of transcripts were Tov in ovaries and Ttes in testes. During further postnatal development, testicular Cyp19 transcript concentrations transiently decreased, but the contributions of different transcript variants basically remained unchanged. However, ovarian Cyp19 transcript concentrations increased by about 100 times, and almost 100% of all Cyp19 transcripts were identified as Tov in adult ovaries. Brains of both sexes showed highest transcript concentrations at P0. However, concentrations in female brains were reduced to adult levels earlier than in male brains. In brains of both sexes, Tbr was found to predominate throughout postnatal life. The results suggest that the mouse Cyp19 gene includes three different promoters that specifically direct expression in ovary, testis, and brain.