Stimulation of adrenal mitogenesis by N-terminal proopiocortin peptides

Although it was generally believed that corticotropin (ACTH) maintained both the size of the adrenal gland and its level of steroid production 1 , there is a growing body of evidence for a specific factor(s) distinct from ACTH which may be responsible for the stimulation of adrenocortical growth and proliferation. While direct neural influences have been proposed to be responsible for the compensatory adrenal growth following unilateral adrenalectomy 2 , several observations have suggested the involvement of peptides such as angiotensin 3 and vasopressin 4 , which have other hormonal effects, or, for example, fibroblast growth factor 5 , which has more general mitogenic actions. Moreover ACTH inhibits cell proliferation in vitro 6–8 , and physiological doses in vivo cannot induce the compensatory growth and hyperplasia seen in the remaining adrenal gland after unilateral adrenalectomy 9 . These observations coupled with the lack of effect of chronic treatment with an ACTH antiserum on adrenal size 10 and the existence of adrenal weight-maintaining activity in the plasma of patients with ACTH-secreting adenomas 11 , have led to the search for a pituitary factor related to ACTH which is capable of stimulating adrenal growth. We now report that peptides derived from the N-terminal non- γ -melanocyte-stimulating hormone (MSH) portion of the precursor of ACTH, proopiocortin, are potent stimulators of adrenal DNA synthesis in vitro and mitosis in vivo and may thus be involved in the physiological control of adrenal growth.