No abstract

Chronic treatment of rats with haloperidol (1.5 mg/kg, once daily) over a period of 7--21 days resulted in a 80--100% increase in the tissue levels of immunoreactive beta-endorphin and in the in vitro release of immunoreactive beta-endorphin from the neurointermediate pituitary. Incorporation of [3H]phenylalanine into isolated neurointermediate pituitaries of haloperidol-treated rats revealed an increase in the amount of label incorporated into the beta-endorphin/ACTH precursor proopiomelanocortin (POMC) to a similar extent (about 80%) but had essentially no effect on the conversion of the precursor into beta-lipotropin and beta-endorphin. Extraction of messenger (m) RNA from neurointermediate pituitaries followed by cell-free translation in a reticulocyte system showed an increase in the total level of translatable mRNA (about 25%). The content of translatable mRNA coding for POMC, however, was increased by 100-150%. Time-course studies revealed a parallelism between the effect of haloperidol on the level of in vitro translatable mRNA coding for POMC and the ability of the drug to increase the concentrations of beta-endorphin in the neurointermediate pituitary. A complete reversal of the effects of haloperidol was seen 2 weeks after discontinuation of the drug. These findings suggest that the chronic blockade of dopaminergic receptors by haloperidol causes a reversible increase in the beta-endorphin biosynthesis in the rat intermediate pituitary at the pretranslational level by markedly increasing the level of translatable mRNA coding for POMC.

No abstract

The levels of dynorphin-(1-13), leucine enkephalin, β-endorphin and vasopressin immunoreactivity (ir-DYN, ir-1-ENK, ir-β-END, ir-VP) have been determined in the anterior and in the neurointermediate lobes of the pituitary of rats subjected to a variety of manipulations. Dehydration of rats by 5 days enforced imbibition of a 2% solution of NaCl resulted in a significant decrease in the levels of ir-DYN, ir-l-ENK and ir-VP, but not in those of ir-β-END in the neurointermediate lobe of the pituitary. In contrast, substitution of drinking water by a solution containing 20 μg/ml dexamethasone for 5 days produced a significant increase in the neurointermediate pituitary content of ir-DYN, ir-l-ENK and ir-VP, whereas levels of ir-β-END remained unaffected. This treatment, however, resulted in a significant fall in the ir-β-END content of the adenopituitary without changing levels of ir-DYN in this structure. Adrenalectomy was associated with a significant decrease in the ir-DYN, ir-VP and ir-l-ENK content of the neurointermediate lobe of the pituitary and a pronounced elevation in the ir-β-END but not ir-DYN content of the adenohypophysis. These observations are indicative that the regulation mechanisms of the functional state of particular endorphins differ between the anterior and neurointermediate lobes of the pituitary. The concomitant alterations in levels of ir-DYN, ir-l-ENK and ir-VP detected suggest that a common or similar mechanism of regulation may exist for these peptides. A common biosynthetic origin, however, appears to be unlikely, since Brattleboro rats which are unable to synthesize vasopressin possess unchanged ir-DYN- and ir-1-ENK levels in the pituitary.

Acute stress promotes the secretion of prolactin (PRL) and of proopiomelanocortin (POMC)-derived peptides, adrenocorticotropic hormone and β-endorphin, from the pituitary into the systemic circulation. The present study evaluates the influence of recurrent stress upon the biosynthetic activity of cells secreting these hormones in the rat. Chronic, intermittent, electrical foot-shock (3 mA 1 s duration, every 5 s for 30 min, twice daily) over a period of 1, 3 or 7 days caused an increase in messenger ribonucleic acid (mRNA) levels coding for POMC in the anterior pituitary. Maximally elevated mRNA levels were achieved after 3 days treatment (about 80% in excess of control values) which showed no further change at 7 days. These elevated levels of POMC mRNA were associated with increased levels of immunoreactive (ir)-β-endorphin in the adenohypophysis following 7 days of stress treatment. In contrast, this treatment did not significantly alter mRNA levels coding for PRL in the anterior pituitary. Similarly, POMC mRNA levels in the intermediate/posterior pituitary were also not significantly altered during exposure to repeated stress. Similar changes in the biosynthesis of the pituitary hormones were seen in rats suffering from chronic arthritic pain for 3 weeks: there was an approximately 80% increase in POMC mRNA levels in the anterior pituitary which was associated with an increase in the levels of ir-β-endorphin in this lobe and an increase in the plasma levels of ir-β-endorphin. In contrast, there were no changes in the levels of mRNA coding for PRL in the adenohypophysis. Moreover, levels of POMC mRNA and of ir-β-endorphin in the intermediate/posterior pituitary remained unchanged. It is concluded that although lactotrophic and corticotrophic cells of the adenohypophysis and corticotrophic cells in the intermediate pituitary respond similarly to acute stress stimuli with an increased secretion, the biosynthetic activity of these cells is differentially modulated under chronic stress.