DEVELOPMENT OF CYTOCHROME-P450 17-ALPHA-HYDROXYLASE (P450C17) MESSENGER-RNA AND ENZYME-ACTIVITY IN NEONATAL OVARIES OF NORMAL AND HYPOGONADAL (HPG) MICE

The cytochrome P450 enzyme 17 alpha-hydroxylase (P450c17) is required for androgen synthesis and therefore regulates substrate supply for ar omatization. In this study, changes in P450c17 activity and mRNA level s 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 nor mal ovaries. This basal level of expression did not change until after day 10 at which time both enzyme activity and mRNA levels increased b y six- to eightfold. In the hpg mouse, levels of P450c17 mRNA were nor mal at birth but did not change significantly during subsequent develo pment and were significantly less than normal by day 15. Results show that there is a low level of gonadotrophin-independent expression of P 450c17 in the ovary at birth and that gonadotrophins are required for the subsequent increase in expression between days 10 and 15. In the o vary, P450c17 is expressed solely in the thecal/interstitial compartme nt and interstitial cells arise in the mouse ovary around day 11. Chan ges in P450c17 are likely, therefore, to be related to gonadotrophin-d ependent development of the interstitial tissue in the mouse. Treatmen t of adult hpg mice with LH and FSH showed that both gonadotrophins ca n act to increase P450c17 activity. Since FSH acts only on the granulo sa cell compartment of the ovary it is likely that FSH acts through a paracrine mechanism to regulate thecal/interstitial cell activity.