Effects of proopiomelanocortin-derived peptides, methionine-enkephalin and forskolin on the maturation of ovine fetal adrenal cells in culture.

The present study examined the effects of peptides derived from the non-ACTH part of proopiomelanocortin (POMC), of met-enkephalin and of forskolin, alone or in combination with ACTH-(1-24), on the development of the ability of ovine fetal adrenal cells to produce both cAMP and corticosteroids in culture. N-POMC-(1-61) amide, gamma 2-melanocyte-stimulating hormone (MSH) and gamma 3-MSH behaved similarly in our system: 1) they increased slightly corticosterone (B) and cortisol (F) production without modification of cAMP output when added alone to the incubation medium, but this effect was observed only after 3 days in culture; 2) they potentiated the steroidogenic response to 10(-11) M ACTH-(1-24) but again only from Day 3 onwards; and 3) a 5-day treatment with the peptides induced fetal adrenal cell maturation resulting in the same enhancement of the B + F production stimulated by 10(-8) M ACTH-(1-24) without modification of the response in both cAMP and pregnenolone (P5). N-POMC-(1-80) and beta-lipotropic hormone (LPH) shared several common features in that, 1) the stimulation of B + F production by each of them alone was always significant and higher than that obtained with the other POMC-derived peptides [except ACTH-(1-24]; 2) they did not potentiate the steroidogenic action of 10(-11) M ACTH-(1-24); and 3) when cells were cultured in their presence for 5 days it resulted in an enhancement of the response to ACTH-(1-24), not only in B + F production but also in cAMP and P5 outputs. No effect of met-enkephalin was observed. The development of cAMP and B + F responses to ACTH-(1-24) provoked by forskolin was very close to that induced by the hormone itself, but forskolin, as opposed to ACTH-(1-24), was unable to induce a desensitization of the cAMP response. These data show that N-POMC-derived peptides can potentiate the acute steroidogenic activity of ACTH-(1-24) on ovine fetal adrenal cells after several days in culture.