Regulation of Adrenocorticotropin/Endorphin-Related Peptide Secretion in Neonatal Rat Pituitary Cultures*

Abstract

In neonatal rat anterior and neurointermediate pituitary lobe explant cultures maintained in complete serum-free medium for up to 3 weeks, the ACTH/endorphin-related peptide content rose about 3-fold. The basal secretion rates of the ACTH/endorphin-related peptides were 0.2-0.3% and 0.6-0.7% of the cell content secreted/h in the anterior and neurointermediate pituitary lobe explants, respectively. Acute treatment of anterior pituitary explants with 10 nM CRF or 0.5 mM (Bu)2-cAMP-0.5 mM isobutylmethylxanthine resulted in about 6- and 9-fold increases in the basal secretion rates, respectively. Pretreatment of the anterior pituitary cultures with 100 nM dexamethasone for 3 days did not alter the basal secretion rate, but drastically reduced both CRF- and cAMP-stimulated release of peptides. In the anterior pituitary explants, chronic CRF treatment resulted in a dose-dependent increase in secreted ACTH/endorphin-related peptides measured in the medium, and this elevation in secretion rate was maintained throughout 12 days of chronic exposure to CRF. Total hormone produced by neonatal anterior pituitary explant cultures was increased 2- to 4-fold by chronic CRF treatment (10 and 100 nM CRF) after 12 days in culture. Compared to the anterior pituitary lobe explants, the neurointermediate pituitary lobe explants were not very responsive to acute or chronic CRF treatment; exposure to 100 nM CRF resulted in about a 2-fold stimulation of the basal secretion rate. Acute exposure of the neurointermediate pituitary lobe explants to 1 microM isoproterenol or cAMP resulted in about 2- and 7-fold increases in the basal secretion rate, respectively. Dexamethasone pretreatment had little effect on either the basal or stimulated release of the ACTH/endorphin-related peptides. These studies demonstrated that some of the tissue-specific regulatory mechanisms involved in ACTH/endorphin-related peptide synthesis and secretion were present in developing explant cultures of anterior and neurointermediate pituitary lobes.