Abstract

Altered hypothalamic-pituitary axis responsiveness is found in a variety of human diseases. The pituicyte's hormone receptor number determines, in part, the magnitude of its response to hypothalamic peptides. The proposed research will test the hypothesis that modulation of receptor biosynthesis contributes to the control of receptor number. Initially, the regulation of anterior pituitary receptor synthesis will be studied with a functional bioassay of mRNA activity based on Xenopus oocyte expression. The well-characterized models of AVP and TRH receptor regulation in the pituitary will be studied. The effect of adrenalectomy and corticosteroids on AVP receptor mRNA activity will be measure. The impact of thyroxine, estradiol and a TRH analog on TRH receptor mRNA activity will be determined. An attempt will be made to clone the cDNAs for the AVP and CRF receptors using expression libraries and anti-idiotype antibodies. If necessary, the AVP receptor can be cloned using the oocyte expression system. Cloned probes will further the investigation of receptor regulation. In situ nucleic acid hybridization and S1 nuclease assay studies of pituitary AVP and CRF receptor modulation will be performed. Studies of these neuro-hormone receptors in degenerative brain diseases will be undertaken.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Physician Scientist Award (K11)
Project #
5K11DK001854-04
Application #
3086449
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1988-09-01
Project End
1993-08-31
Budget Start
1991-09-01
Budget End
1992-08-31
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Mount Sinai School of Medicine
Department
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10029

  Publications

Davidson, J S; Flanagan, C A; Becker, I I et al. (1994) Molecular function of the gonadotropin-releasing hormone receptor: insights from site-directed mutagenesis. Mol Cell Endocrinol 100:9-14
Chi, L; Zhou, W; Prikhozhan, A et al. (1993) Cloning and characterization of the human GnRH receptor. Mol Cell Endocrinol 91:R1-6
Tsutsumi, M; Zhou, W; Millar, R P et al. (1992) Cloning and functional expression of a mouse gonadotropin-releasing hormone receptor. Mol Endocrinol 6:1163-9
Probst, W C; Snyder, L A; Schuster, D I et al. (1992) Sequence alignment of the G-protein coupled receptor superfamily. DNA Cell Biol 11:1-20
Snyder, L A; Roberts, J L; Sealfon, S C (1991) Alternative transcripts of the rat and human dopamine D3 receptor. Biochem Biophys Res Commun 180:1031-5
Snyder, L A; Roberts, J L; Sealfon, S C (1991) Distribution of dopamine D2 receptor mRNA splice variants in the rat by solution hybridization/protection assay. Neurosci Lett 122:37-40
Sealfon, S C; Gillo, B; Mundamattom, S et al. (1990) Gonadotropin-releasing hormone receptor expression in Xenopus oocytes. Mol Endocrinol 4:119-24
Sealfon, S C; Laws, S C; Wu, J C et al. (1990) Hormonal regulation of gonadotropin-releasing hormone receptors and messenger RNA activity in ovine pituitary culture. Mol Endocrinol 4:1980-7
Sealfon, S C; Mundamattom, S; Gillo, B (1990) Modulation of calcium mobilization by guanosine 5'-O-(2-thiodiphosphate) in Xenopus oocytes. FEBS Lett 269:135-8
Autelitano, D J; Snyder, L; Sealfon, S C et al. (1989) Dopamine D2-receptor messenger RNA is differentially regulated by dopaminergic agents in rat anterior and neurointermediate pituitary. Mol Cell Endocrinol 67:101-5

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