Abstract

The major objectives of this research are to characterize dopamine, adrenergic and opiate receptors involved in neuroendocrine regulation of LH and prolactin at both the level of the anterior pituitary and median eminence. Dopamine receptors in the anterior pituitary will be solubilized and purified. Antibodies will be generaged to dopamine receptor in rabbits and by the monoclonal antibody techniques. The antibodies as well as derivatized dopaminergic antagonist linked to ferritin will be used to label dopamine receptor in the anterior pituitary and hypothalamus at the light and electron microscopic levels. Modulation, distribution, aggregation and internalization of anterior pituitary dopamine receptors will also be studied. Stable hybrid cell lines will be established which secrete prolactin and express cyclase or non-cyclase dependent dopamine receptors or beta-adrenergic recptors. Dispersed anterior pituitary cells will be maintained in long term cultures on extracellular matrix. These cultures will be used to study the role of dopamine in regulating responsiveness of mammotrophs to the suppression of prolactin release. Responsiveness will be correlated with dopamine receptor number and affinity in whol cell radioligand assays.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
3R01HD008924-11S1
Application #
3311013
Study Section
Endocrinology Study Section (END)
Project Start
1978-04-01
Project End
1986-11-30
Budget Start
1986-08-01
Budget End
1986-11-30
Support Year
11
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Tsai, Pei-San; Moenter, Suzanne M; Postigo, Hector R et al. (2005) Targeted expression of a dominant-negative fibroblast growth factor (FGF) receptor in gonadotropin-releasing hormone (GnRH) neurons reduces FGF responsiveness and the size of GnRH neuronal population. Mol Endocrinol 19:225-36
Yoshida, Hiroshi; Beltran-Parrazal, Luis; Butler, Paul et al. (2003) Lowering cyclic adenosine-3',5'-monophosphate (cAMP) levels by expression of a cAMP-specific phosphodiesterase decreases intrinsic pulsatile gonadotropin-releasing hormone secretion from GT1 cells. Mol Endocrinol 17:1982-90
Paruthiyil, Sreenivasan; eL Majdoubi, Mohammed; Conti, Marco et al. (2002) Phosphodiesterase expression targeted to gonadotropin-releasing hormone neurons inhibits luteinizing hormone pulses in transgenic rats. Proc Natl Acad Sci U S A 99:17191-6
Weiner, R I; Charles, A (2001) Regulation of gonadotropin-releasing hormone release by cyclic AMP signalling pathways. Growth Horm IGF Res 11 Suppl A:S9-15
Vitalis, E A; Costantin, J L; Tsai, P S et al. (2000) Role of the cAMP signaling pathway in the regulation of gonadotropin-releasing hormone secretion in GT1 cells. Proc Natl Acad Sci U S A 97:1861-6
Sakakibara, H; Conti, M; Weiner, R I (1998) Role of phosphodiesterases in the regulation of gonadotropin- releasing hormone secretion in GT1 cells. Neuroendocrinology 68:365-73
Tsai, P S; Werner, S; Weiner, R I (1995) Basic fibroblast growth factor is a neurotropic factor in GT1 gonadotropin-releasing hormone neuronal cell lines. Endocrinology 136:3831-8
Martinez de la Escalera, G; Choi, A L; Weiner, R I (1995) Signaling pathways involved in GnRH secretion in GT1 cells. Neuroendocrinology 61:310-7
Mellon, S H; Miller, W L; Bair, S R et al. (1994) Steroidogenic adrenocortical cell lines produced by genetically targeted tumorigenesis in transgenic mice. Mol Endocrinol 8:97-108
Milenkovic, L; D'Angelo, G; Kelly, P A et al. (1994) Inhibition of gonadotropin hormone-releasing hormone release by prolactin from GT1 neuronal cell lines through prolactin receptors. Proc Natl Acad Sci U S A 91:1244-7

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