Ethanol can increase circulating levels of ACTH and cortisol through modulation of corticotrophin-releasing factor (CRF) signaling. Ethanol can potentially increase CRF-R1 and Gsα-mediated signaling by promoting phosphorylation of type 7 adenylyl cyclase (AC7) by protein kinase Cδ. Pronko et al. investigated ethanol action at AC7 by creating transgenic mice overexpressing AC7 and by knocking down AC7. As predicted, AC7 overexpression produced greater plasma levels of ACTH and cortisol after ethanol challenge than either wild-type or knockdown mice, with females producing higher levels than males. It is noteworthy that females had significantly higher levels of cortisol in circulation than males, suggesting that the adrenal tissue of females may be more responsive to high levels of ACTH. These results establish AC7 as an integral component of signaling between CRF-R1 and ACTH release under ethanol intoxication and/or stress. Polymorphisms in the ADCY7 gene may promote differential expression of AC7, which in turn may make certain individuals more susceptible to increased circulating ACTH and cortisol following alcohol consumption or emotional stress.
See article at J Pharmacol Exp Ther 2010, 334:44–52.
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