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By: Donny Dumani

LH Receptor, StAR Protein, and Steroidogenic Enzyme mRNAs Are Overexpressed in Thecal Cells From Polycystic Ovaries. By: Donny Dumani. What is PCOS?. - Disorder in Women of Childbearing Age - Chronic Anovulation - Accumulation of Small Follicles

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By: Donny Dumani

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  1. LH Receptor, StAR Protein, and Steroidogenic Enzyme mRNAs Are Overexpressed in Thecal Cells From Polycystic Ovaries By: Donny Dumani

  2. What is PCOS? - Disorder in Women of Childbearing Age - Chronic Anovulation - Accumulation of Small Follicles - Excess Androgen: Testosterone, DHEA, Androstenedione and Dihydrotestosterone

  3. Why Increased Androgen Secretion? - Hyperplasia? Not all follicles - Increased Steroidogenic Capacity per Cell? RECENT DATA: PCOS thecal cells exhibit stable hyperandrogenic phenotype & increased CYP17 promoter activity. Can this suggests a molecular basis for thecal hyperactivity?

  4. What’s the next step? • To determine whether there is abnormal gene expression in thecal cells from PCOS If key genes in androgen biosynthesis are overexpressed?

  5. How to accomplish this goal? • Measure the levels of LH receptor, StAR protein, CYP11A, and CYP17 mRNAs from thecal cells from PCOS ovaries and the ovaries of regularly cycling control women.

  6. Subjects and Methods Ovarian Tissue Specimens • 12 PCOS & 24 regular cycling control • Microdissection Reverse Transcriptase-PCR Assay

  7. Results • Was the pattern of LH receptor, StAR, CYP17, and CYP11A mRNA expression altered in PCOS thecal cells? Higher Expression than Normal?

  8. Next Results? • To determine whether mRNAs varied in a coordinated fashion? Any shifting or increasing pattern of LH receptor, StAR, CYP11A mRNAs vs. CYP17A mRNA?

  9. Discussion • What conclusions can this coordinate overexpression tell us? • What is a valid molecular basis for thecal hyperactivity? • Altered regulatory element? • Altered intracellular signaling pathway?

  10. Final Thoughts • New insight into pathophysiology of PCOS • First evidence of thecal cell hyperstimulation in PCOS • What possible hormonal mechanism contributes to this hyperstimulation and overexpression of thecal mRNAs? • Mild hyperinsulinemia from insulin resistance

  11. A Possible Treatment for PCOS? • About 50% of women with these conditions develop PCOS • Insulin-sensitizing drugs have shown to decrease androgen levels • Related to a decrease in ovarian CYP17A activity • Improvement with fertility and menstrual cycles Hyperinsulinemia likely important in PCOS!

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