Enhanced activity of the beta-endorphinergic system in the anterior and neurointermediate lobe of the rat pituitary after chronic treatment with ethanol liquid diet.

Chronic treatment of rats with ethanol liquid diet over a period of two weeks resulted in a pronounced increase in the activity of the beta-endorphinergic system in the anterior and neurointermediate lobe of the pituitary. In the anterior pituitary, the in vitro incorporation of [3H]tyrosine into beta-endorphin and its precursor peptides beta-lipotropin and pro-opiomelanocortin was enhanced by 350, 100 and 135%, respectively. In contrast, the in vitro biosynthesis of total proteins was not altered, indicating that the ethanol-induced stimulatory effects on the beta-endorphinergic system were not due to a nonspecific enhancement of protein synthesis. The in vitro release of beta-endorphin-related peptides from the anterior pituitary was increased; the tissue concentrations, however, remained unchanged. In the neurointermediate pituitary, the in vitro incorporation of [3H]tyrosine into beta-endorphin also was stimulated by more than 50% in response to chronic ethanol treatment, whereas the biosynthesis of total proteins was unaffected. The ethanol-induced stimulation of the beta-endorphin system in the neurointermediate pituitary, however, did not appear to result in an increased formation of beta-endorphin-like peptides with opiate activity, as the concentrations of alpha-N-acetylated forms of beta-endorphin were found to be increased, whereas those of nonacetylated forms were markedly decreased. This is suggestive for an ethanol-induced stimulation of the alpha-N-acetylation of beta-endorphin, a modification that inactivates the peptide in all its opiate-like properties.

Differential effects of acute and chronic ethanol treatment on particular opioid peptide systems in discrete regions of rat brain and pituitary.

Acute ethanol treatment induced a significant increase in the tissue levels of immunoreactive (ir-) Met-enkephalin in hypothalamus, striatum and midbrain, but not in hippocampus. Levels of ir-dynorphin, ir-alpha-neo-endorphin and ir-beta-endorphin were not found to be significantly altered in brain and pituitary. Chronic ethanol treatment (by the use of ethanol liquid diet) resulted in a more than 50% decrease of the tissue levels of ir-dynorphin and ir-alpha-neo-endorphin in hypothalamus and hippocampus, while both peptides remained unchanged in midbrain, striatum, adenohypophysis and neurointermediate pituitary. In contrast, ir-met-enkephalin was decreased in striatum and hypothalamus, but unaffected in midbrain and hippocampus. Levels or ir-beta-endorphin remained unchanged in the brain and in the pituitary. However, the de novo biosynthesis of beta-endorphin and its prohormones beta-lipotropin and pro-opiomelanocortin was increased in the intermediate pituitary and to an even more pronounced degree, in the adenohypophysis, after chronic treatment of rats with ethanol liquid diet, nevertheless, the amounts of opiate-active beta-endorphin were found to be reduced in both lobes of the pituitary: In the adenohypophysis, this was due to a retardation of the enzymatic processing of beta-endorphin from its precursor beta-lipotropin, while in the intermediate pituitary the alpha-N-acetylation of beta-endorphin to opiate-inactive alpha-N-acetyl-beta-endorphin was stimulated. In conclusion, acute and chronic ethanol treatment caused selective alterations on different opioid peptide systems within distinct areas of the rat brain and pituitary.

Dynorphin-related immunoreactive peptides in rat brain and pituitary.

Antisera recognizing dynorphin 1-13, but not other opioid peptides with a high avidity, have been generated in rabbits. Using a radioimmunoassay technique levels of dynorphin-immunoreactivity (dyn-ir) have been measured in the brain and pituitary of rats. The concentrations of dyn-ir ranged from a maximum in the intermediate/posterior lobe of the pituitary (about 1200 pmol/g) to a minimum in the cerebellum (about 1 pmol/g) as follows: pituitary intermediate/posterior lobe greater than adenohypophysis greater than hypothalamus greater than hippocampus = striatum = midbrain = thalamus = medulla/pons greater than cortex greater than cerebellum. Gel-filtration of hypothalamic extracts revealed 4 immunoreactive components with apparent molecular weights (MW) of 3500, 2400, 1300 and less than 1000 daltons, respectively. No dyn-ir was found to elute as dynorphin1-13 (MW = 1700). The 2400 and 1300 dalton materials showed opiate-like activity on the guinea-pig ileum longitudinal muscle preparation, indicating that a substantial part of the dyn-ir measured represented biologically active material.