Adrenal regeneration in the rat is mediated by mitogenic N-terminal pro-opiomelanocortin peptides generated by changes in precursor processing in the anterior pituitary

ABSTRACT In order to investigate the role of N-terminal proopiomelanocortin (N-POMC) in adrenal regeneration after bilateral adrenal enucleation (hereafter referred to as enucleation) rats 13 days after enucleation were injected (200 μl s.c. plus 200 μl i.p.) at 08.00 and 20.00 h with normal rabbit serum (NRS), an ACTH antiserum or an N-POMC antiserum. On the next day the animals were injected with colchicine, killed and mitotic figures in adrenal histological sections counted. The same treatment was given to rats 20 days after enucleation. Only the N-POMC antiserum significantly diminished adrenal mitotic activity 14 and 21 days after enucleation (P < 0·01 and 0·05 respectively) when compared with NRS-treated enucleated rats, whereas plasma corticosterone levels in rats 14 days after enucleation were significantly (P < 0·005) decreased only by treatment with ACTH antiserum. To determine whether the mitogenic N-POMC peptides involved in adrenal regeneration originated from the pituitary intermediate lobe, 0·9% (w/v) NaCl or ergocryptine (10 mg/kg body weight) was administered s.c. twice daily to rats between 7 and 13 days after enucleation. On day 14, adrenal mitotic activity and plasma levels of ACTH and N-POMC were not significantly different between ergocryptine and saline-treated enucleated rats, whereas α-MSH levels in ergocryptine-treated enucleated rats were significantly (P < 0·02) decreased. Increases in N-POMC content of the pituitary lobe accompanied those of ACTH in animals 7, 10, 14 and 21 days after enucleation (P < 0·01 compared with sham-treatment). Anterior lobes from rats 10 days after enucleation or from adrenalectomized rats showed raised ACTH and N-POMC levels compared with sham-treated animals, whereas α-MSH content in the anterior lobe of enucleated rats was significantly (P < 0·005) decreased. Adrenalectomized animals had raised (P < 0·005) amounts of α-MSH compared with sham-treated animals. Plasma levels of ACTH and N-POMC were significantly (P < 0·01) raised in rats 10 days after enucleation or in adrenalectomized rats compared with those in sham-treated animals, whereas α-MSH levels were raised (P < 0·005) only in adrenalectomized rats. Sephadex G-75 chromatography of anterior lobe extracts obtained 10 days after surgery from sham-treated, enucleated and adrenalectomized rats was performed. In sham-treated animals the main N-POMC-immunoreactive peaks were located at the elution positions of N-POMC(1–95) and N-POMC (1–74), whereas in enucleated rats the bulk of the N-POMC immunoreactivity was located in a third peak which eluted at the position of synthetic N-POMC (1–48). In adrenalectomized rats a peak coinciding with the N-POMC(1–48) standard could also be detected, but the bulk of the N-POMC immunoreactivity corresponded to the N-POMC(1–95) and N-POMC(1–74) peaks. Perfusates from dispersed rat anterior pituitary cells from rats 10 days after enucleation or sham-operation were also chromatographed. The profile of N-POMC immunoreactivity was essentially the same as that in the anterior lobe extract. Chromatography of plasma samples from ergocryptine-treated enucleated rats revealed a peak accounting for N-POMC (1–74) and a peak coinciding with N-POMC(1–48). It was concluded that N-POMC peptides are physiologically important in adrenal regeneration and that, in this condition, mitogenically active N-POMC peptides are generated from the anterior lobe and not from the intermediate lobe of the pituitary gland. This implies a change in the mode of anterior lobe N-POMC processing in adrenal regeneration. J. Endocr. (1988) 116, 207–216