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A Novel Function of Bone Morphogenetic Protein-15 in the Pituitary: Selective Synthesis and Secretion of FSH by Gonadotropes

Department of Reproductive Medicine, University of California at San Diego, School of Medicine, La Jolla, California 92093-0633

Address all correspondence and requests for reprints to: Shunichi Shimasaki, Ph.D., Department of Reproductive Medicine, University of California at San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, California 92093-0633. E-mail: sshimasaki{at}ucsd.edu

Bone morphogenetic protein-15 (BMP-15) has been known to be an oocyte-specific factor and regulate granulosa cell functions. Here, we report that BMP-15 is also expressed in the well established gonadotrope cell line, LßT2 and mouse pituitary tissue. Interestingly, BMP-15 stimulates FSHß subunit transcription in LßT2 cells without affecting LHß and GnRH receptor transcription. These findings, therefore, suggest a possible autocrine control mechanism selective for FSHß synthesis by BMP-15. Moreover, BMP-15 exerts a potent and selective stimulation of FSH, but not LH, secretion by primary pituitary cells. Taken together, we hypothesize that BMP-15 could play a physiological role in the monotropic rise of FSH secretion by the pituitary during the estrous and menstrual cycle. These findings, together with the previous evidence of a negative regulation of FSH receptor expression by BMP-15 in the ovary, may constitute a major role in female fertility.

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