ELEVATED LEVELS OF N-TERMINAL PROOPIOMELANOCORTIN PEPTIDES IN FETAL SHEEP PLASMA MAY CONTRIBUTE TO FETAL ADRENAL-GLAND DEVELOPMENT AND THE PRE-PARTURIENT CORTISOL SURGE

Parturition in sheep is initiated by a rapid rise in fetal plasma cort isol. There is some controversy as to the exact nature of the drive fo r this pre-partum cortisol surge and it is thought that factors other than ACTH may act in concert to stimulate the development of die fetal adrenal gland. We have investigated the concentrations of ACTH and ot her peptides derived from pro-opiomelanocortin (POMC) in the circulati on of fetal sheep during the final part of gestation, using specific 2 -site immunoradiometric assays. The expected rise in fetal cortisol wa s seen with an 880% (p<0.01) increase in concentration of this hormone between the initial measurement period (110-119 days gestation) and t he final period (139-147 days). Fetal plasma ACTH increased less drama tically (I 37%; p<0.03) during this time. The most surprising finding was the presence of very high relative concentrations of the N-termina l POMC peptide N-POMC(1-77) in the fetal circulation. Initially the co ncentration was 289 +/- 66 pmol/l compared to ACTH concentrations of 6 .4 +/- 0.8 pmol/l. In the final week of gestation N-POMC(I-77) levels, although still high, had declined to 188 +/- 35 pmol/l (ACTH having i ncreased to 13.7 + 2.2 pmol/l). Fetal plasma Y3-MSH was found to incre ase towards the end of gestation when the concentration of N-POMC(1-77 ) was declining, suggesting some cleavage of the latter. We postulate that the N-POMC(1-77) and its fragments, acting in concert with ACTH, play a vital role in stimulating the development of the fetal adrenal cortex and provide the additional drive to the adrenal gland required to stimulate parturition.