Abstract

Bone Morphogenic Protein-15 is a newly discovered member of the TGF-P superfamily which is secreted by oocytes. Recent studies from our laboratory have identified granulosa cells as a target cell type for this growth factor, and have demonstrated that in these cells, BMP-15 is capable of stimulating mitosis and inhibiting FSH receptor mRNA expression. These findings establish the novel concept that this oocyte- derived factor is involved in regulating two major aspects of follicular development: stimulating proliferation and inhibiting FSH-dependent cytodifferentiation. The goal of the present study is to elucidate the molecular mechanisms responsible for BMP-15 biological activity in granulosa cells.
Specific Aim 1 Identify the cell surface receptors for BMP-15 on granulosa cells and elucidate the subsequent downstream signaling pathway.
Specific Aim 2 Determine whether BMP-15 reduces FSH binding sites on the surface of granulosa cells and explore the mechanism by which BMP-15 inhibits FSH receptor gene expression.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HD041320-01
Application #
6404944
Study Section
Reproductive Biology Study Section (REB)
Program Officer
Taymans, Susan
Project Start
2002-02-28
Project End
Budget Start
2001-09-01
Budget End
2002-08-31
Support Year
1
Fiscal Year
2001
Total Cost
$34,832
Indirect Cost

  Institution

Name
University of California San Diego
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Chen, Pao-Yang; Ganguly, Amit; Rubbi, Liudmilla et al. (2013) Intrauterine calorie restriction affects placental DNA methylation and gene expression. Physiol Genomics 45:565-76
Garg, Meena; Thamotharan, Manikkavasagar; Dai, Yun et al. (2013) Glucose intolerance and lipid metabolic adaptations in response to intrauterine and postnatal calorie restriction in male adult rats. Endocrinology 154:102-13
Dai, Yun; Thamotharan, Shanthie; Garg, Meena et al. (2012) Superimposition of postnatal calorie restriction protects the aging male intrauterine growth- restricted offspring from metabolic maladaptations. Endocrinology 153:4216-26
Hashimoto, Osamu; Moore, R Kelly; Shimasaki, Shunichi (2005) Posttranslational processing of mouse and human BMP-15: potential implication in the determination of ovulation quota. Proc Natl Acad Sci U S A 102:5426-31
Moore, R Kelly; Shimasaki, Shunichi (2005) Molecular biology and physiological role of the oocyte factor, BMP-15. Mol Cell Endocrinol 234:67-73
Otsuka, Fumio; Moore, R Kelly; Wang, Xia et al. (2005) Essential role of the oocyte in estrogen amplification of follicle-stimulating hormone signaling in granulosa cells. Endocrinology 146:3362-7
Liao, Wu Xiang; Moore, R Kelly; Shimasaki, Shunichi (2004) Functional and molecular characterization of naturally occurring mutations in the oocyte-secreted factors bone morphogenetic protein-15 and growth and differentiation factor-9. J Biol Chem 279:17391-6
Shimasaki, Shunichi; Moore, R Kelly; Otsuka, Fumio et al. (2004) The bone morphogenetic protein system in mammalian reproduction. Endocr Rev 25:72-101
Moore, R Kelly; Erickson, Gregory F; Shimasaki, Shunichi (2004) Are BMP-15 and GDF-9 primary determinants of ovulation quota in mammals? Trends Endocrinol Metab 15:356-61
Liao, Wu Xiang; Moore, R Kelly; Otsuka, Fumio et al. (2003) Effect of intracellular interactions on the processing and secretion of bone morphogenetic protein-15 (BMP-15) and growth and differentiation factor-9. Implication of the aberrant ovarian phenotype of BMP-15 mutant sheep. J Biol Chem 278:3713-9

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