P-227: Functional Analysis of The I.a,I.b, I.c and I.d (PII) Promoters of CYP19 (aromatase) Gene in Granulosa Cells of Polycystic Ovaries Patients and The Role of Letrozole and Antisensearom on CYP19 Gene Expression Inhibition

Background: The key enzyme of estrogen biosynthesis, aromatase cytochrome P450,is encoded by the CYP19 gene.CYP19 plays an important role in the development,function,an regulation of the female reproduction cycle. Thus, it is the potential candidate gene affecting fertility performance in human. CYP19 transcripts are expressed mainly in the ovary,testes,breast,adipose tissue and brain. Tissue expression of the CYP19 gene is determined by the use of tissue-specific promoters.The object of the present study was to determine first,the distribution of various exon-specific CYP19 transcripts and second,the inhibitory effect of letrozole and antisense aromatase on CYP19 gene expression level in granulosa cells of polycystic ovaries (PCO) patients. Materials and Methods: CYP19 transcript levels on four promoters were measured from granulosa cells of PCO patients by competitive RT-PCR and the effect of letrozole and antisensearom on potent promoters were evaluated by real-time PCR. Results: Antisensearom was potent inhibitor of CYP19 transcription, while letrozole inhibited moderately.Promoter1.d(PII) proved the most potent in driving gene expression.Promoter1. c displayed moderate activity,while promoters 1.a and 1.b were weak. Conclusion: Two regulator regions of promoters 1.d(PII) and 1.c relevant to CYP19 expression in human granulosa cells in ovary.Letrozole and antisensearom modulate transcription through these regions.