Mechanisms involved in the transduction of neural signals and the control of tissue specific gene expression are studied. The pineal and pituitary glands are used as model systems. The details of the chemical and ionic components of transmembrane signal processing and of neural and tissue specific regulation of gene expression are analyzed. Signal transduction in the pineal gland is of special interest because cAMP and cGMP are regulated by dual receptor mechanisms which appear to interact at the level of regulation of adenylyl and guanylyl cyclases. One leg of these pathways activates these enzymes via GTP binding regulatory proteins, similar to Gsalpha. In the area of the neural and developmental control of gene expression, a major advance has been made by the cloning of the gene encoding serotonin N-acetyltransferase. This will make it possible to study how neural signals regulate expression of this gene in vertebrates and how the activity of this enzyme is controlled. The major hormonal product of the pineal gland is melatonin. Melatonin has been found to block GnRH induced increase in [Ca++]i and to block GnRH-induced depolarization. Melatonin appears to act on a subpopulation of GnRH-sensitive cells. It is clear from associated studies that melatonin acts through an action on the calcium, not cyclic AMP, and that the effect of melatonin on calcium is secondary to an effect on membrane potential.

Project Start
Project End
Budget Start
Budget End
Support Year
25
Fiscal Year
1995
Total Cost
Indirect Cost
City
State
Country
United States
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Klein, David C; Bailey, Michael J; Carter, David A et al. (2010) Pineal function: impact of microarray analysis. Mol Cell Endocrinol 314:170-83
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Ganguly, Surajit; Grodzki, Cristina; Sugden, David et al. (2007) Neural adrenergic/cyclic AMP regulation of the immunoglobulin E receptor alpha-subunit expression in the mammalian pinealocyte: a neuroendocrine/immune response link? J Biol Chem 282:32758-64
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Zheng, Weiping; Schwarzer, Dirk; Lebeau, Aaron et al. (2005) Cellular stability of serotonin N-acetyltransferase conferred by phosphonodifluoromethylene alanine (Pfa) substitution for Ser-205. J Biol Chem 280:10462-7
Kim, Jong-So; Coon, Steven L; Blackshaw, Seth et al. (2005) Methionine adenosyltransferase:adrenergic-cAMP mechanism regulates a daily rhythm in pineal expression. J Biol Chem 280:677-84
Iuvone, P Michael; Tosini, Gianluca; Pozdeyev, Nikita et al. (2005) Circadian clocks, clock networks, arylalkylamine N-acetyltransferase, and melatonin in the retina. Prog Retin Eye Res 24:433-56
Gaildrat, Pascaline; Moller, Morten; Mukda, Sujira et al. (2005) A novel pineal-specific product of the oligopeptide transporter PepT1 gene: circadian expression mediated by cAMP activation of an intronic promoter. J Biol Chem 280:16851-60
Nguyen, Andrew D; Pan, Chi-Jiunn; Shieh, Jeng-Jer et al. (2005) Increased cellular cholesterol efflux in glycogen storage disease type Ia mice: a potential mechanism that protects against premature atherosclerosis. FEBS Lett 579:4713-8

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