Luteal dysfunction with insufficient luteal progesterone production is one cause of human infertility and is associated with spontaneous recurrent miscarriage. Such dysfunction has been attributed to reduced lifespan of the corpus luteum or suboptimal luteal function. Alterations in the endocrine or paracrine milieu of the corpus luteum can alter its function or lifespan. The long term goal of the proposed studies is to understand the influence of estrogen on luteal cell function and regression. Preliminary data implicate estrogen receptor alpha induction coincident with periovulatory follicular differentiation. The proposed studies are designed to test the effect of estrogen (and other relevant hormones) on induction of estrogen receptor alpha, steroidogenic capacity of luteal cells, and luteal cell regression in the porcine model.
Specific aims i nclude: 1) To test the hypothesis that estradiol, follicle-stimulating hormone (FSH), and/or luteinizing hormone (LH) upregulate the mRNA and protein levels of estrogen receptor alpha but not estrogen receptor beta in differentiating granulosa cells, 2) To determine the effect of estradiol on the expression of critical genes mediating progesterone production by early, midphase, and late phase luteal cells. The expression of the low density lipoprotein receptor, steroidogenic acute regulatory protein, p450 cholesterol side-chaincleavage enzyme, and 3beta-hydroxysteroid dehydrogenase genes will be evaluated, 3) To determine the effect of estradiol on PGF2alpha induced caspase-3 activation and apoptosis in luteal cells isolated from corpora lutea prior to, during, and after functional regression. The expression of estrogen receptor alpha and beta mRNA and/or protein will be also be evaluated to correlate their presence with estradiol function. These studies will provide evidence that reduction in estradiol at specific stages in the luteal phase may adversely affect steroidogenic genes and facilitate regression.

National Institute of Health (NIH)
National Institute on Minority Health and Health Disparities (NIMHD)
Exploratory Grants (P20)
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Special Emphasis Panel (ZMD1)
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Benedict College
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Blake, Charles A; McCoy, George L; Hui, Yvonne Y et al. (2011) Perinatal exposure to low-dose DE-71 increases serum thyroid hormones and gonadal osteopontin gene expression. Exp Biol Med (Maywood) 236:445-55
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Blake, Charles A; Brown, Lewis M; Duncan, Mark W et al. (2005) Estrogen regulation of the rat anterior pituitary gland proteome. Exp Biol Med (Maywood) 230:800-7
Benoit, Allison M; McCoy, George L; Blake, Charles A (2005) Localization of fertility factor SP22 to specific cell types within the anterior pituitary gland. Exp Biol Med (Maywood) 230:721-30

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