Effect of N-proopiomelanocortin (1-77) and (1-49) infusions on adrenal expression of cyclin D1 in the fetal sheep.

In the sheep, there is a rapid increase in fetal adrenal growth and steroidogenesis during the last 10-15 days gestation. Recently, we have shown that infusion of POMC 1-77 increases fetal adrenal growth but does not significantly alter fetal plasma cortisol concentrations. Phosphorylation and inactivation of the pRB protein, which is required for progression into the DNA synthetic phase of the cell-cycle is conducted by a holoenzyme, for which cyclin D1 gene encodes the rate-limiting regulatory subunit. To further elucidate the mechanisms by which POMC 1-77 regulates adrenal growth, we therefore examined adrenal expression of the rate-limiting cell cycle protein, cyclin D 1, from fetuses infused for 48 hr with POMC 1-77 (n = 6), POMC 1-49 or Saline (n = 6). There was no significant difference in the adrenal expression of cyclin D1 mRNA levels between POMC 1-77, 1-49 and saline infused fetuses. There was no significant correlation between cyclin D1 (4.0 Kb) and adrenal weight. In summary, these data do not demonstrate that the rate-limiting cell cycle protein, cyclin D1, is activated to stimulate adrenal growth following infusion of POMC 1-77 in the fetal sheep in late gestation.