The long-term goals of this project are to identify the specific subcellular processes that intervene between luteinizing hormone releasing hormone (LHRH) - receptor interaction and the secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the pituitary gland and to determine how these processes are regulated by LHRH and modulated by other hormones. In the proposed studies, we will examine calcium movement into the gonadotrope and the consequence to the immediate gonadotropin secretory event and to the self priming response. In addition, the secretory granule will be examined as one site at which regulation of both immediate release and self priming may converge.
The specific aims are to: 1) Establish a pituitary cell culture system for assessing rapid changes in LH and FSH secretory activity as well as LHRH self priming and for performing in situ radiolabeling studies. Superfusion of pituitary pieces and of pituitary cells cultured on coverslips including cultures enriched for gonadotropes will be used. 2) Identify the specific calcium channel types modulated by LHRH which are involved in the secretory event in the gonadotrope. The probes for this will be a series of divalent cations of varying channel permeabilities and channel-specific blockers; the endpoints will be changes in gonadotropin secretory activity. 3) Determine the consequence of a change in cytosolic (calcium) to selected intracellular mediators of LHRH action. Cyclic AMP generation will be used as a measure to compare cAMP-mediated regulation of LHRH self priming with the augmentation of secretion stimulated by barium and zero calcium/EGTA media. The ability of barium and other divalent cations to affect the activity of protein kinase C and one of its substrates will be evaluated. 4) Determine the characteristics and regulation of p36 and p35 (protein kinase C and tyrosine-protein kinase substrates in pituitary secretory granules). This will include establishing the identity of pituitary p36/p35 with calpactinI/calpactinII by immunoblotting, tryptic peptide mapping and phosphoamino analysis, defining the calcium/phospholipid dependent association of p36/p35 with secretory granules and plasma membranes in the gonadotrope, and identifying the agonist-stimulated pathway regulating phosphorylation of p36/p35 in the pituitary gland. These studies will provide insight into the mechanisms of action of LHRH in that modulation of specific intracellular events will be related to physiological effects of the hormone.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Reproductive Biology Study Section (REB)
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University of California Davis
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Yuen, Tony; Choi, Soon Gang; Pincas, Hanna et al. (2012) Optimized amplification and single-cell analysis identify GnRH-mediated activation of Rap1b in primary rat gonadotropes. Mol Cell Endocrinol 350:10-9
Waring, Dennis W; Turgeon, Judith L (2009) Ca2+-activated K+ channels in gonadotropin-releasing hormone-stimulated mouse gonadotrophs. Endocrinology 150:2264-72
Waring, Dennis W; Turgeon, Judith L (2006) Estradiol inhibition of voltage-activated and gonadotropin-releasing hormone-induced currents in mouse gonadotrophs. Endocrinology 147:5798-805
Turgeon, Judith L; Carr, Molly C; Maki, Pauline M et al. (2006) Complex actions of sex steroids in adipose tissue, the cardiovascular system, and brain: Insights from basic science and clinical studies. Endocr Rev 27:575-605
Turgeon, Judith L; Waring, Dennis W (2006) Differential expression and regulation of progesterone receptor isoforms in rat and mouse pituitary cells and LbetaT2 gonadotropes. J Endocrinol 190:837-46
Turgeon, Judith L; McDonnell, Donald P; Martin, Kathryn A et al. (2004) Hormone therapy: physiological complexity belies therapeutic simplicity. Science 304:1269-73
Turgeon, J L; Shyamala, G; Waring, D W (2001) PR localization and anterior pituitary cell populations in vitro in ovariectomized wild-type and PR-knockout mice. Endocrinology 142:4479-85
Turgeon, J L; Waring, D W (2001) Luteinizing hormone secretion from wild-type and progesterone receptor knockout mouse anterior pituitary cells. Endocrinology 142:3108-15
Turgeon, J L; Waring, D W (2000) Progesterone regulation of the progesterone receptor in rat gonadotropes. Endocrinology 141:3422-9
Turgeon, J L; Van Patten, S M; Shyamala, G et al. (1999) Steroid regulation of progesterone receptor expression in cultured rat gonadotropes. Endocrinology 140:2318-25

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