BILATERAL ADRENAL ENUCLEATION-INDUCED CHANGES IN ADENOHYPOPHYSEAL PROOPIOMELANOCORTIN (POMC)-RELATED PEPTIDES SYNTHESIS AND SECRETION - A COMPARATIVE-STUDY WITH ADRENALECTOMIZED RATS

The aim of the present study was to elucidate the modulatory effect of transient changes in endogenous glucocorticoids, occurring after bila teral adrenal enucleation (ENUC), on anterior pituitary (AP) proopiome lanocortin (POMC)-derived peptides synthesis and output in rats. For t his purpose, adult female rats were either bilaterally ENUC, adrenalel ectomized (ADX), or sham-operated (SHAM) and killed by decapitation 2, 7, 14, and 21 days after surgery. Trunk blood was collected for measu rements of ACTH, beta-endorphin (beta-END) and corticosterone (B) conc entrations; APs were quickly dissected for the determination of ACTH, beta-endorphin (beta-END)-like (beta-END-LI) and gamma(3)-MSH contents and adrenal glands were removed and submitted to histological study. The results indicate that ENUC and ADX increased AP POMC-related pepti des synthesis and release in association with changes in the AP proces sing of peptides belonging to the N-terminal (gamma(3)-MSH), mid (ACTH ) and C-terminal (beta-LPH/ENDs) portions of POMC, While ADX abolished plasma B levels, ENUC induced a transient (day 2) decrease in plasma B concentrations which returned to SHAM levels at 7 days after surgery , These data tallied with the histological observations carried out, i ndicating a time-dependent regenerative process of the adrenal which w as completed by three weeks after ENUC. There was a different pattern in plasma ACTH and beta-END levels between ENUC and ADX; maximal plasm a peptide levels were found 7-14 days after ENUC, then falling down to SHAM values at 21 days post ENUC. Conversely, there was a constant in crement in plasma peptide levels up to 21 days after ADX, At 2 days af ter both ENUC and ADX all peptides measured in the AP were lower than SHAM values, thus reflecting a rapid corticotrope secretion. Thereafte r, 7 or more days after surgery, AP peptide content in ADX rats increa sed, in a time-related fashion, up to 21 days after surgery, Only beta -END-LI showed a similar AP content to that of the SHAM group, thereaf ter indicating a preferential cleavage of POMC to beta-END long after ADX (21 days), ENUC rats showed increased AP POMC peptides content thr oughout the whole time, and it was significantly different from SHAM a nd ADX values 14 days postsurgery. Interestingly, we found an incremen t in AP gamma(3)-MSH, a peptide which is preferentially synthesized in the intermediate lobe of the rat pituitary, in both ENUC and ADX situ ations, Our results further indicate that: 1) glucocorticoids, from re generating adrenal origin, induce a fast negative feedback mechanism o n AP secretion, and 2) there might be a delayed inhibitory action of n ewly synthesized corticosteroids on higher levels of the central nervo us system. The lack of glucocorticoids (ADX) clearly corroborates a pe rsistent enhancement of AP POMC-related peptides synthesis and secreti on. The differences in AP processing of POMC between ENUC and ADX migh t be due to qualitative/quantitative changes in hypotalamic ACTH secre tagogues output. (C) 1997, Editrice Kurtis.