A novel function of bone morphogenetic protein-15 in the pituitary: selective synthesis and secretion of FSH by gonadotropes

Endocrinology. 2002 Dec;143(12):4938-41. doi: 10.1210/en.2002-220929.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activins / pharmacology
  • Animals
  • Bone Morphogenetic Protein 15
  • Bone Morphogenetic Protein 6
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins / pharmacology
  • Cell Line
  • Cells, Cultured
  • Female
  • Follicle Stimulating Hormone / biosynthesis*
  • Follicle Stimulating Hormone / metabolism*
  • Follicle Stimulating Hormone, beta Subunit / genetics
  • Gene Expression
  • Gene Expression Regulation / drug effects
  • Growth Differentiation Factor 9
  • Inhibin-beta Subunits / pharmacology
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Luteinizing Hormone / biosynthesis
  • Luteinizing Hormone / metabolism
  • Luteinizing Hormone, beta Subunit / genetics
  • Male
  • Mice
  • Ovary / chemistry
  • Pituitary Gland / chemistry
  • Pituitary Gland / physiology*
  • Pituitary Gland, Anterior / metabolism
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, FSH / genetics
  • Receptors, LHRH / genetics
  • Transcription, Genetic / drug effects
  • Transforming Growth Factor beta*

Substances

  • Bmp15 protein, mouse
  • Bmp15 protein, rat
  • Bmp6 protein, mouse
  • Bmp6 protein, rat
  • Bmp7 protein, rat
  • Bone Morphogenetic Protein 15
  • Bone Morphogenetic Protein 6
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins
  • Follicle Stimulating Hormone, beta Subunit
  • Gdf9 protein, mouse
  • Gdf9 protein, rat
  • Growth Differentiation Factor 9
  • Intercellular Signaling Peptides and Proteins
  • Luteinizing Hormone, beta Subunit
  • RNA, Messenger
  • Receptors, FSH
  • Receptors, LHRH
  • Transforming Growth Factor beta
  • activin A
  • Activins
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • Inhibin-beta Subunits