Mechanisms involved in the transduction of neural signals and the control of tissue specific gene expression are studies. 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 quanylyl cyclases. One leg of these pathways activates these enzymes via GTP binding regulatory proteins, similar to Gs alpha. In the area of the neural and developmental control of gene expression, advances have been made in purifying N- acetyltransferase and hydroxyindole-O-methyltransferase, and in isolating cDNA clones coding for these enzymes. It has been found that three HIOMT mRNA molecules exist, which appear to be the result of alternative splicing; one contains a truncated LINE sequence in the coding region. Recent studies have extended second messenger analysis into the role of transcription factors in signal transduction in the pineal gland. 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.

Project Start
Project End
Budget Start
Budget End
Support Year
24
Fiscal Year
1994
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
Kim, Jong-So; Coon, Steven L; Weller, Joan L et al. (2009) Muscleblind-like 2: circadian expression in the mammalian pineal gland is controlled by an adrenergic-cAMP mechanism. J Neurochem 110:756-64
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
Moller, Morten; Rath, Martin F; Klein, David C (2006) The perivascular phagocyte of the mouse pineal gland: an antigen-presenting cell. Chronobiol Int 23:393-401
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
Ganguly, Surajit; Weller, Joan L; Ho, Anthony et al. (2005) Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. Proc Natl Acad Sci U S A 102:1222-7
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

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