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Bone Morphogenetic Protein-2 (BMP-2) Increases Gene Expression of FSH Receptor and Aromatase and Decreases Gene Expression of LH Receptor and StAR in Human Granulosa Cells


Osamu Yoshino and Yutaka Osuga
Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan
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Citation Shi J, Yoshino O, Osuga Y, Koga K, Hirota Y, Nose E, Nishii O, Yano T, Taketani Y. Bone morphogenetic protein-2 (BMP-2) increases gene expression of FSH receptor and aromatase and decreases gene expression of LH receptor and stAR in human granulosa Cells. Am J Reprod Immunol 2011; 65: 421–427

Problem  A growing body of evidence indicates that bone morphogenetic protein (BMP) cytokines play a key role in female fertility in mammals. BMP-2 is known to be expressed in the ovary of many species. In the present study, we examined the expression and function of BMP-2 in the human ovary.

Method of Study  BMP-2 mRNA expression in the human ovary was evaluated by in situ hybridization. Human granulosa cells were obtained from in vitro fertilization patients. Human granulosa cells were cultured with recombinant BMP-2 or human chorionic gonadotrophin (HCG), followed by RNA extraction.

Results  BMP-2 expression was detected in granulosa cells of antral follicles but not of corpus luteum. The in vitro study showed that BMP-2 induced follicular stimulating hormone (FSH) receptor and aromatase expression, while decreasing luteinizing hormone (LH) receptor and steroidogenic acute regulatory protein expression in human granulosa cells. HCG decreased gene expression of BMP-2 and increased BMP and activin membrane-bound inhibitor (BAMBI), an antagonist of BMP-2.

Conclusion  Expression and disappearance of BMP-2 might contribute to folliculogenesis and luteinization by regulating gonadotropin receptor expression in human granulosa cells. HCG can modulate BMP-2 function by controlling BMP-2 and BAMBI expression.