Further evidence that N-terminal pro-opiomelanocortin peptides are involved in adrenal mitogenesis

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Abstract
In order to demonstrate the mitogenic effects of N-terminal pro-opiomelanocortin (N-POMC) peptides on the adrenal glands further, female rats with bilateral adrenal enucleation (hereafter referred to as enucleation) were hypophysectomized 11 days after enucleation and injected twice daily with 5 μg purified human N-POMC(1–28), ACTH(1–24) or 0·9% (w/v) NaCl. On day 14 after enucleation, rats were injected with colchicine and, after killing, their adrenal glands weighed, fixed and mitotic counts in histological sections assessed. Plasma corticosterone was measured fluorometrically. In other experiments, rats 7 days after enucleation were hypophysectomized and implanted with osmotic minipumps delivering 5 μg purified N-POMC(1–28) per day. On day 14 after enucleation, animals were treated as above. Collagenase-dispersed adrenal cells were incubated with purified or synthetic N-POMC(1–28) or synthetic N-POMC (1–36) (1–300 nmol/l) and [3H]thymidine incorporation into DNA was determined. Intact female rats were implanted with osmotic minipumps delivering 8 μg purified or synthetic N-POMC(1–28)/day, 8 μg synthetic N-POMC(1–36)/day or saline alone. Mitotic counts were performed on histological sections. Both s.c. injection or continuous delivery from minipumps of purified N-POMC(1–28) partially prevented the atrophy of regenerating adrenal glands after hypophysectomy (s.c. injection of N-POMC: 2·29 ± 0·92 mitoses/section compared with 0·52 ± 0·39 for controls; minipump delivery: 5·02 ± 0·97 compared with 0·13 ± 0·05; P < 0·01 for both experiments). ACTH did not augment mitotic activity in enucleated– hypophysectomized rats but significantly increased plasma concentrations of corticosterone in s.c. injection experiments. Adrenal weights were not significantly changed. Both purified and synthetic N-POMC(1–28) increased thymidine incorporation in incubated adrenal cells, the synthetic peptide being less potent than the purified peptide. Whilst synthetic and purified N-POMC(1–28) significantly increased mitotic counts in histological sections of intact adrenal glands after chronic delivery from minipumps, N-POMC(1–36) had no significant effect. It was concluded that N-POMC(1–28) can partially reverse the adrenal atrophy in enucleated rats after hypophysectomy, whereas ACTH is mitotically inactive in the same situation. The low potency of the synthetic peptides compared with purified N-POMC(1–28) preparations reported in this study could be due to differences in secondary structure. J. Endocr. (1988) 116, 201–206