Development of cytochrome P450 aromatase mRNA levels and enzyme activity in ovaries of normal and hypogonadal (hpg) mice

Abstract

The cytochrome P450 aromatase (P450arom) enzyme is required for bioconversion of androgen to oestrogen. In this study ovarian P450arom mRNA and enzyme activity have been measured during development in normal mice and hypogondal (hpg) mice which lack circulating gonadotrophins. A semi-quantitative reverse transcription-PCR (RT-PCR) technique was used to measure cytochrome P450arom mRNA levels and aromatase enzyme activity was measured directly. Using RT-PCR, P450arom mRNA was detectable in the adult mouse ovary and also in the uterus, kidney, brain and skeletal muscle but not in cardiac smooth muscle. In the normal mouse, P450arom mRNA was detectable in the ovary on the day of birth (day 1) and levels increased significantly up to day 15 with the most marked changes seen between days 1 and 5. Aromatase activity was also detectable at all ages in the ovary and increased significantly between days 1 and 7. In ovaries from hpg mice, normal levels of P450arom mRNA were present on day 1 but there was no significant change in P450arom mRNA at later ages up to day 15. These results show that in the newborn mouse ovary, which contains only primordial follicles, there is a basal expression of P450arom mRNA which is not gonadotrophin-dependent. After 1 day, however, gonadotrophins are required for normal expression of ovarian P450arom and this coincides with development of primary and secondary follicles.