The objective of the Specialized Cooperative Centers Program in Reproduction Research (SCCPRR) at the University of Maryland Medical Center is to conduct innovative basic and clinical research in the reproductive sciences and to apply the knowledge gained from these studies to improve understanding of the etiology and treatment of infertility in women. A multidisciplinary experimental approach will be taken in this program to study function of the pituitary-ovarian- uterine axis as related to the central theme on cellular remodeling. In Project I (Karen A. Gregerson, PI), the physiological importance of an inwardly-rectifying, dopamine-activated pituitary K+ channel to prolactin secretion and fertility will be determined in transgenic mice in which the function of this novel membrane channel is interrupted by dominant-negative mutation. In Project II (Gerald J. Pepe, PI), the regulatory role of estrogen on fetal ovarian follicular and oocyte development and the impact on fertility will be assessed in baboons in which placental estrogen synthesis is suppressed in utero by administration of a novel aromatase inhibitor. In Project III (Robert D. Koos, PI), the physiological role of members of the fibroblast growth factor family, bFGF and keratinocyte growth factor, on ovarian and uterine function and fertility will be studied in transgenic mice in which the truncated, dominant-negative FGF receptors are spatially and temporally overexpressed. A combined clinical-basic research study is proposed in Project IV (Eugene D. Albrecht, PI), in which the roles of estrogen and progesterone, acting via vascular endothelial growth/ permeability factor and bFGF, on endometrial angiogenesis and fertility will be investigated in vivo in baboons and in vitro in the human endometrium. Each of the research projects will draw heavily upon the Cell Immunocytochemistry/In Situ Hybridization Core (Gloria E. Hoffman, PI) for the cellular localization of regulatory peptides and steroid hormone receptors. Integration of the scientific effort in this SCCPRR will be achieved through the thematic focus on cellular remodeling, common technological molecular approaches, and an established tradition of collaborative research.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HD036207-05
Application #
6521060
Study Section
Special Emphasis Panel (ZHD1-PRG-G (08))
Program Officer
Leppert, Phyllis C
Project Start
1998-04-01
Project End
2004-03-31
Budget Start
2002-04-01
Budget End
2004-03-31
Support Year
5
Fiscal Year
2002
Total Cost
$938,093
Indirect Cost
Name
University of Maryland Baltimore
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Pepe, Gerald J; Lynch, Terrie J; Albrecht, Eugene D (2013) Regulation of baboon fetal ovarian development by placental estrogen: onset of puberty is delayed in offspring deprived of estrogen in utero. Biol Reprod 89:132
Bonagura, Thomas W; Zhou, Hui; Babischkin, Jeffery S et al. (2011) Expression of P-450 aromatase, estrogen receptor ? and ?, and ?-inhibin in the fetal baboon testis after estrogen suppression during the second half of gestation. Endocrine 39:75-82
Bonagura, Thomas W; Aberdeen, Graham W; Babischkin, Jeffery S et al. (2010) Divergent regulation of angiopoietin-1 and -2, Tie-2, and thrombospondin-1 expression by estrogen in the baboon endometrium. Mol Reprod Dev 77:430-8
Entezam, Ali; Lokanga, Adihe Rachel; Le, Wei et al. (2010) Potassium bromate, a potent DNA oxidizing agent, exacerbates germline repeat expansion in a fragile X premutation mouse model. Hum Mutat 31:611-6
Albrecht, Eugene D; Pepe, Gerald J (2010) Estrogen regulation of placental angiogenesis and fetal ovarian development during primate pregnancy. Int J Dev Biol 54:397-408
Molitoris, Kristin Happ; Kazi, Armina A; Koos, Robert D (2009) Inhibition of oxygen-induced hypoxia-inducible factor-1alpha degradation unmasks estradiol induction of vascular endothelial growth factor expression in ECC-1 cancer cells in vitro. Endocrinology 150:5405-14
Pepe, Gerald J; Lynch, Terrie J; Davies, William A et al. (2009) Regulation of baboon fetal pituitary prolactin expression by estrogen. Biol Reprod 80:1189-95
Babischkin, Jeffery S; Bonagura, Thomas W; Udoff, Laurence C et al. (2009) Estrogen stimulates the human endometrium to express a factor(s) that promotes vascular smooth muscle cell migration as an early step in microvessel remodeling. Endocrine 35:81-8
Albrecht, Eugene D; Lane, Malcolm V; Marshall, Gary R et al. (2009) Estrogen promotes germ cell and seminiferous tubule development in the baboon fetal testis. Biol Reprod 81:406-14
Rockwell, L Christie; Koos, Robert D (2009) Dexamethasone enhances fertility and preovulatory serum prolactin levels in eCG/hCG primed immature rats. J Reprod Dev 55:247-51

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