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ABSTRACT
The cytochrome P450 enzyme 17α-hydroxylase (P450c17) is required for androgen synthesis and therefore regulates substrate supply for aromatization. In this study, changes in P450c17 activity and mRNA levels were measured during ovarian development in the normal mouse and in the hypogonadal (hpg) mouse which lacks circulating gonadotrophins. At birth, low levels of P450c17 activity and mRNA were detectable in normal ovaries. This basal level of expression did not change until after day 10 at which time both enzyme activity and mRNA levels increased by six- to eightfold. In the hpg mouse, levels of P450c17 mRNA were normal at birth but did not change significantly during subsequent development and were significantly less than normal by day 15. Results show that there is a low level of gonadotrophin-independent expression of P450c17 in the ovary at birth and that gonadotrophins are required for the subsequent increase in expression between days 10 and 15. In the ovary, P450c17 is expressed solely in the thecal/interstitial compartment and interstitial cells arise in the mouse ovary around day 11. Changes in P450c17 are likely, therefore, to be related to gonadotrophin-dependent development of the interstitial tissue in the mouse. Treatment of adult hpg mice with LH and FSH showed that both gonadotrophins can act to increase P450c17 activity. Since FSH acts only on the granulosa cell compartment of the ovary it is likely that FSH acts through a paracrine mechanism to regulate thecal/interstitial cell activity.
Search for other papers by S A Gray in
Google Scholar
PubMed
Search for other papers by M A Mannan in
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PubMed
Search for other papers by P J O'Shaughnessy in
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PubMed
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 hypogonadal (hpg) mice which lack circulating gonadotrophins. A semi-quantitative reverse transcription-PCR (RTPCR) 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 [ill] 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 gonadotrophindependent. After 1 day, however, gonadotrophins are required for normal expression of ovarian P450arom and this coincides with development of primary and secondary follicles.
