Restraint stress and exogenous corticosterone differentially alter sensitivity to the sedative-hypnotic effects of ethanol in inbred long-sleep and inbred short-sleep mice.
Anterior pituitary corticotrope function was analyzed in the long sleep (LS) and short sleep (SS) lines of mice selectively bred for differences in sensitivity to ethanol. In vivo challenge with acute ethanol or CRH administration or the stress of novel handling resulted in a more pronounced increase in serum corticosterone levels in LS mice compared with SS mice. Likewise, in vivo administration of ethanol resulted in 3-fold higher levels of anterior pituitary pro-ACTH/endorphin mRNA in LS mice compared with SS mice. However, this differential regulation of the HPA axis during in vivo analysis was not observed during in vitro studies of anterior pituitary corticotrope function. Primary cultures of LS and SS anterior pituicytes responded appropriately but equivalently to a variety of secretagogues known to stimulate anterior pituitary ACTH secretion. These secretagogues included CRH (10 nM), dibutyryl-cAMP (1 mM), vasopressin (100 nM), and phorbol 12-myristate 13-acetate (10 nM). Ethanol had no direct stimulatory effect on pituitary ACTH secretion. Quantitation of anterior pituitary corticotrope peptide biosynthesis was determined by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of extracts from [35S]methionine-labeled anterior pituitary explants and from [35S]methionine-labeled primary cultures of anterior pituitary cells. LS mice pro-ACTH/endorphin biosynthesis in pituitary explants was 2-fold greater than pro-ACTH/endorphin biosynthesis in SS mice pituitary explants. However, in culture, isolated from hypothalamic and adrenal factors, the LS anterior pituitary pro-ACTH/endorphin biosynthetic rate became equivalent to the SS anterior pituitary pro-ACTH/endorphin biosynthetic rate.(ABSTRACT TRUNCATED AT 250 WORDS)