We hypothesized that sustained biosynthesis of proopiomelanocortropin (POMC) from the anterior pituitary during chronic stress might result in enhanced membrane adenylyl cyclase (AC) activity, facilitating amplification of the CRH signal despite falling numbers of CRH receptors. Therefore, we investigated the effects of stress on AC activity in anterior pituitaries from Sprague-Dawley rats exposed to stress. Following 12 h of intermittent, cold, swim stress, stressed rats had plasma corticosterone levels that were 10 fold higher than in nonstressed animals and showed a 40% reduction in the specific binding of 125I-CRH to anterior pituitary membranes. Moreover, stressed rats showed a 3 fold increase in anterior pituitary POMC mRNA levels. To test the hypothesis that factors released during stress enhanced the AC signal transduction system, thereby leading to increased POMC gene expression, we measured anterior pituitary cAMP and assayed AC activity from membranes prepared from anterior pituitary of control and stressed rats. Levels of cAMP were 2 fold higher in pituitaries from stressed rats compared to controls. The significant increase in cAMP was accompanied by a significant increase of AC activity. To test what component(s) of the AC complex are altered by stress, type I and II AC mRNA as well as Gsα, Gi(1-3)α and Gβ protein levels were determined. Type II AC mRNA was significantly increased 1.7 fold in stressed rats compared with controls, whereas no consistent alteration in G-protein levels were detected. Enhanced AC activity following cold swim stress was not limited to the pituitary, to one line of rat, nor one type of stress. In Fisher rats, both cold swim and restraint stress enhanced AC activity in the pituitary and in the frontal cortex. In summary, stress enhances AC activity in the anterior pituitary. The increase in AC activity is associated with increased steady state levels of type II AC mRNA. Factor(s) released during stress may enhance AC signal transduction and allow for persistent elevation in POMC gene expression despite the inhibitory influences of glucocorticoids.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)