Abstract

The maintenance of corpus luteum vascularization, growth and steroidogenesis in the pregnant rat is a complex process involving pituitary, placental and ovarian hormones. Estradiol, formed in the luteal cell from either endogenous or placental androgen substrates. acts locally to stimulate blood supply, cell hypertrophy and steroidogenesis of the corpus luteum previously exposed to prolactin from either pituitary or placenta.
The first aim of this study is to investigate the molecular mechanism by which estradiol affects vascularization and growth of the corpus luteum. We will investigate the possibility that estradiol enhances blood supply to the corpus luteum by increasing the content and mRNA for basic fibroblast growth factor, the luteal angiogenic factor. Whether the requirement for prolactin and estradiol for the optimal growth of the rat corpus luteum reflects interaction of these two hormones on the production and action of insulin-like growth factor-I will be determined. We will examine the possibility that estradiol enhances cholesterol availability for progesterone biosynthesis by increasing the formation of both HMG-CoA reductase, the key enzyme in cholesterol biosynthesis, and Sterol Carrier Protein 2, the molecule responsible for cholesterol transport to the mitochondria. The significance and the role of estrogen induced changes in calcium-calmodulin and calcium- phospholipid-dependent phosphorylation of specific proteins in subcellular fractions will be investigated. Since estradiol biosynthesis by the corpus luteum depends upon placental androgens from mid-pregnancy, we will determine the reason why the placenta does not synthesize androgen early in pregnancy and determine, throughout placental development, the content and mRNA levels of cytochrome P450scc and P45017 alpha, the enzymes responsible for progesterone and androgen biosynthesis. Finally, we will investigate the mechanism by which LH, estradiol and calcium- calmodulin controls placental steroidogenesis in the rat.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HD011119-18
Application #
2196783
Study Section
Special Emphasis Panel (NSS)
Project Start
1978-01-01
Project End
1998-03-31
Budget Start
1995-04-01
Budget End
1996-03-31
Support Year
18
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
University of Illinois at Chicago
Department
Physiology
Type
Schools of Medicine
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612

  Publications

Le, Jamie A; Wilson, Heather M; Shehu, Aurora et al. (2012) Generation of mice expressing only the long form of the prolactin receptor reveals that both isoforms of the receptor are required for normal ovarian function. Biol Reprod 86:86
Shehu, Aurora; Albarracin, Constance; Devi, Y Sangeeta et al. (2011) The stimulation of HSD17B7 expression by estradiol provides a powerful feed-forward mechanism for estradiol biosynthesis in breast cancer cells. Mol Endocrinol 25:754-66
Le, J A; Wilson, H M; Shehu, A et al. (2011) Prolactin activation of the long form of its cognate receptor causes increased visceral fat and obesity in males as shown in transgenic mice expressing only this receptor subtype. Horm Metab Res 43:931-7
Devi, Y Sangeeta; Seibold, Anita M; Shehu, Aurora et al. (2011) Inhibition of MAPK by prolactin signaling through the short form of its receptor in the ovary and decidua: involvement of a novel phosphatase. J Biol Chem 286:7609-18
Devi, Y Sangeeta; Shehu, Aurora; Halperin, Julia et al. (2009) Prolactin signaling through the short isoform of the mouse prolactin receptor regulates DNA binding of specific transcription factors, often with opposite effects in different reproductive issues. Reprod Biol Endocrinol 7:87
Bachelot, Anne; Beaufaron, Julie; Servel, Nathalie et al. (2009) Prolactin independent rescue of mouse corpus luteum life span: identification of prolactin and luteinizing hormone target genes. Am J Physiol Endocrinol Metab 297:E676-84
Devi, Y Sangeeta; Shehu, Aurora; Stocco, Carlos et al. (2009) Regulation of transcription factors and repression of Sp1 by prolactin signaling through the short isoform of its cognate receptor. Endocrinology 150:3327-35
Shehu, Aurora; Mao, Jifang; Gibori, Gil B et al. (2008) Prolactin receptor-associated protein/17beta-hydroxysteroid dehydrogenase type 7 gene (Hsd17b7) plays a crucial role in embryonic development and fetal survival. Mol Endocrinol 22:2268-77
Halperin, Julia; Devi, Sangeeta Y; Elizur, Shai et al. (2008) Prolactin signaling through the short form of its receptor represses forkhead transcription factor FOXO3 and its target gene galt causing a severe ovarian defect. Mol Endocrinol 22:513-22
Li, Feixue; Devi, Y Sangeeta; Bao, Lei et al. (2008) Involvement of cyclin D3, CDKN1A (p21), and BIRC5 (Survivin) in interleukin 11 stimulation of decidualization in mice. Biol Reprod 78:127-33

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