HYPERADRENOCORTICISM AND FOOD RESTRICTION-INDUCED LIFE EXTENSION IN THE RAT - EVIDENCE FOR DIVERGENT REGULATION OF PITUITARY PROOPIOMELANOCORTIN RNA AND ADRENOCORTICOTROPIC HORMONE BIOSYNTHESIS

The increased diurnal elevation of plasma corticosterone (B) induced b y food restriction (FR) may play a role in the life span extension of FR. We investigated whether FR alters adrenocorticotropic hormone (ACT H) and proopiomelanocortin (POMC) mRNA levels in plasma and anterior p ituitary (AP), since these molecules both regulate and can be suppress ed by B. Measurements were made in 3-month-old male Fischer 344 rats t hat had been fed ad libitum (AL) or FR (60% of AL calories) since 6 we eks of age. Plasma B was 2-fold higher in FR rats in the PM samples, b ut did not differ in AM samples. By contrast, plasma ACTH did not diff er in the PM samples of FP and AL rats and was 20% lower in AM samples (p <.05) of FR rats. AP content of ACTH was 50% lower in FR rats in b oth AM and PM samples (p <.01). In contrast, AP contents of POMC mRNA, primary transcript, and processing intermediate were not reduced in F R rats, and PM content of POMC primary transcript was elevated in FR r ats (p <.05). The reduced pituitary and plasma ACTH of FR rats may be the consequence of their elevated plasma B levels. This study also sug gests that factors other than elevated ACTH account for FR-induced hyp eradrenocorticism. These results also indicate that POMC mRNA and ACTH biosyntheses are differentially regulated in FR rats.