STRESS ALTERS ADENYLYL-CYCLASE ACTIVITY IN THE PITUITARY AND FRONTAL-CORTEX OF THE RAT

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 ampl ification of the CRH signal despite falling numbers of CRH receptors. Therefore, we investigated the effects of stress on AC activity in ant erior pituitaries from Sprague-Dawley rats exposed to stress. Followin g 12 h of intermittent, cold, swim stress, stressed rats had plasma co rticosterone levels that were 10 fold higher than in nonstressed anima ls and showed a 40% reduction in the specific binding of I-125-CRH to anterior pituitary membranes. Moreover, stressed rats showed a 3 fold increase in anterior pituitary POMC mRNA levels. To test the hypothesi s that factors released during stress enhanced the AC signal transduct ion system, thereby leading to increased POMC gene expression, we meas ured anterior pituitary cAMP and assayed AC activity from membranes pr epared 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 signi ficant increase of AC activity. To test what component(s) of the AC co mplex are altered by stress, type I and II AC mRNA as well as Gsalpha, Gi(1-3)alpha and Gbeta protein levels were determined. Type II AC mRN A was significantly increased 1.7 fold in stressed rats compared with controls, whereas no consistent alteration in G-protein levels were de tected. Enhanced AC activity following cold swim stress was not limite d to the pituitary, to one line of rat, nor one type of stress. In Fis her rats, both cold swim and restraint stress enhanced AC activity in the pituitary and in the frontal cortex. In summary, stress enhances A C activity in the anterior pituitary. The increase in AC activity is a ssociated with increased steady state levels of type II AC mRNA. Facto r(s) released during stress may enhance AC signal transduction and all ow for persistent elevation in POMC gene expression despite the inhibi tory influences of glucocorticoids.