A novel function of bone morphogenetic protein-15 in the pituitary: selective synthesis and secretion of FSH by gonadotropes.
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, LbetaT2 and mouse pituitary tissue. Interestingly, BMP-15 stimulates FSHbeta subunit transcription in LbetaT2 cells without affecting LHbeta and GnRH receptor transcription. These findings, therefore, suggest a possible autocrine control mechanism selective for FSHbeta 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.
Otsuka
Fumio
F
Department of Reproductive Medicine, University of California at San Diego, School of Medicine, La Jolla, California 92093-0633, USA.
Shimasaki
Shunichi
S
D028341:Activins / Q000494:pharmacology; D000818:Animals; D055430:Bone Morphogenetic Protein 15; D055418:Bone Morphogenetic Protein 6; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D005640:Follicle Stimulating Hormone / Q000096:biosynthesis* / Q000378:metabolism*; D037201:Follicle Stimulating Hormone, beta Subunit / Q000235:genetics; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D055429:Growth Differentiation Factor 9; D028322:Inhibin-beta Subunits / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D007986:Luteinizing Hormone / Q000096:biosynthesis / Q000378:metabolism; D037101:Luteinizing Hormone, beta Subunit / Q000235:genetics; D008297:Male; D051379:Mice; D010053:Ovary / Q000737:chemistry; D010902:Pituitary Gland / Q000737:chemistry / Q000502:physiology*; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011962:Receptors, FSH / Q000235:genetics; D011966:Receptors, LHRH / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta
C525902:Bmp15 protein, mouse; C525904:Bmp15 protein, rat; C525817:Bmp6 protein, mouse; C525818:Bmp6 protein, rat; C525821:Bmp7 protein, rat; D055430:Bone Morphogenetic Protein 15; D055418:Bone Morphogenetic Protein 6; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D037201:Follicle Stimulating Hormone, beta Subunit; C525898:Gdf9 protein, mouse; C525899:Gdf9 protein, rat; D055429:Growth Differentiation Factor 9; D036341:Intercellular Signaling Peptides and Proteins; D037101:Luteinizing Hormone, beta Subunit; D012333:RNA, Messenger; D011962:Receptors, FSH; D011966:Receptors, LHRH; D016212:Transforming Growth Factor beta; C422405:activin A; D028341:Activins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D028322:Inhibin-beta Subunits