RT Journal Article
SR Electronic
T1 Type 7 Adenylyl Cyclase-Mediated Hypothalamic-Pituitary-Adrenal Axis Responsiveness: Influence of Ethanol and Sex
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 44
OP 52
DO 10.1124/jpet.110.166793
VO 334
IS 1
A1 Sergey P. Pronko
A1 Laura M. Saba
A1 Paula L. Hoffman
A1 Boris Tabakoff
YR 2010
UL http://jpet.aspetjournals.org/content/334/1/44.abstract
AB Although ethanol has been considered to be an anxiolytic agent, consumption of ethanol has also been shown to increase plasma adrenocorticotropin and glucocorticoids. The corticotrophin-releasing factor (CRF) receptor 1α (CRF-R1) is a G protein-coupled receptor that activates adenylyl cyclase (AC), leading to adrenocorticotropin (and subsequently glucocorticoid) release into the circulation. There are nine members of the membrane-bound AC family, and the type 7 AC (AC7) is most sensitive to ethanol, which enhances the responsiveness of AC7 to G protein-coupled receptor activation. We determined the time course of ethanol's effect on plasma adrenocorticotropin and corticosterone levels in male and female AC7 transgenic (Adcy7huTG) mice (in which AC7 is overexpressed in neural tissue) and AC7 heterozygous knockdown [Adcy7(+/−)] mice (in which AC7 is underexpressed in neural tissue), and their respective littermate controls [wild type (WT)]. CRF-R1 mRNA and mRNA and protein for different forms of ACs were measured by using gene expression arrays, quantitative reverse transcription-polymerase chain reaction, and immunoblotting in pituitaries of all animals. Our results demonstrated increased levels of AC7 in pituitary of Adcy7huTG mice and decreased levels in pituitary of Adcy7(+/−) mice compared with WT animals. Male and female Adcy7huTG mice displayed higher plasma adrenocorticotropin and corticosterone levels than WT and/or Adcy7(+/−) mice after ethanol injection. Female mice displayed higher adrenocorticotropin and corticosterone levels after ethanol injection than males, regardless of genotype. The data provide evidence for an integral role of AC7 in the increase of plasma adrenocorticotropin and corticosterone levels during alcohol intoxication. Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics