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Title: EXPRESSION OF CYTOCHROME P450 1A1, AN ESTROGEN HYDROXYLASE, IN OVARIAN GRANULOSA CELLS IS DEVELOPMENTALLY REGULATED

Author
item LEIGHTON J K - MS HERSHEY PK MED CTR, PA
item CANNING SANDRA - MS HERSHEY PK MED CTR, PA
item Guthrie, Howard
item HAMMOND J M - MS HERSHEY PK MED CTR, PA

Submitted to: Journal of Steroid Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/15/1995
Publication Date: N/A
Citation: N/A

Interpretive Summary: The incidence of long infertile periods and low ovulation rate in female swine is a serious economic problem that can occur after weaning or during environmental stress. Pigs that fail to be in estrus or fail to conceive increase producer costs by 25%. Ovarian estradiol production is an important intraovarian regulator of follicle growth and oocyte maturation. However, little work in the pig has been done to relate expression of the cytochrome P450 hydroxylase enzymes to regulation of estradiol metabolism which is vital to these ovarian functions. Of all P450 hydroxylases tested only CYP 1A1 mRNA was in expressed cultured immortalized or primary granulosa cells and in tissue from preovulatory porcine follicles. Immature follicles did not contain CYP 1A1 mRNA. These results provide new knowledge to scientists that is required to investigate the role of estradiol metabolism in relation to follicular development.

Technical Abstract: We report the analysis of porcine ovarian granulosa cells for the expression of several known hepatic estrogen hydroxylase RNAs. Of the P450s examined, only CYP 1A1 RNA was detected. Accordingly, the regulation of this mRNA was studied. The RNA for CYP 1A1 was dramatically and completely induced within two hours after exposure of immortalized granulosa cells to 3-methylcholanthrene (3MC) and expression could be inhibited with uM phorbol myristate acetate. This message was also inducible by 3MC in cultured primary granulosa cells isolated from immature and developing follicles. Dexamethasone increased the relative expression of CYP 1A1 RNA in 3MC treated cells. In the absence of 3MC, the CYP 1A1 RNA was expressed in cultured granulosa cells from developing but not immature follicles, indicating developmental regulation of this enzyme. Further support for developmental regulation was provided by studies which detected the appearance of CYP 1A1 RNA during growth of ovarian follicles in vivo. This is the first report identifying a specific P450 estrogen hydroxylase RNA in ovarian granulosa cells.