High precursor level in maternal blood results from the alternate mode of proopiomelanocortin processing in human placenta

OBJECTIVE ACTH-producing non-pituitary tumours are often associated with al tered precursor processing, particularly in the most aggressive ones, Since placental tissue is characterized by its ability to express the proopiomel anocortin (POMC) gene and rapid cellular proliferation, we examined whether intact POMC could be released physiologically during human gestation. SUBJECTS One hundred and fifty six normal pregnant women, 12 with multiple pregnancies, and 23 non-pregnant controls, Twenty-eight women were studied in the immediate postpartum period. MEASUREMENTS We measured plasma POMC levels with a specific immunoradiometr ic assay (IRMA) using a combination of antibodies directed against ACTH and beta endorphin. Results obtained with this first IRMA were confirmed in 22 subjects with a second assay using the same beta endorphin antibody and a more distal antibody directed against the N-terminal fragment of POMC. Reve rse transcription-PCR detected full length, pituitary-like, POMC mRNA in hu man placenta, RESULTS Plasma POMC was undetectable (<60 U/ml) in 23 normal subjects. In n ormal monofetal pregnancies, POMC became detectable in most women by the th ird month and then increased steadily until midgestation: 168 +/- 108 (U/ml ; mean +/- SD) between 12 and 15 weeks, 190 +/- 103 between 16 and 19 weeks , 324 +/- 180 between 20 and 23 weeks, 276 +/- 171 between 24 and 27 weeks, 292 +/- 177 between 28 and 31 weeks, 290 +/- 235 between 32 and 35 weeks a nd 308 +/- 210 between 36 weeks and parturition, Plasma POMC was significan tly higher in multiple pregnancies with very high levels in three triplet-b earing mothers: 671, 941, and 1731 U/ml at 31, 33 and 32 weeks, respectivel y. POMC levels felt quickly in post partum, becoming undetectable in five o f 13 women on day 1, seven of eight on day 2 and five of six on day 3, Plas ma POMC displayed no diurnal variation, was not suppressed by glucocorticoi d administration and did not correlate with plasma ACTH or cortisol, In con trast, plasma POMC positively correlated with plasma CRH. CONCLUSIONS Pregnancy is the only condition in which POMC is produced and r eleased physiologically, similar in some respects to the ectopic ACTH syndr ome. POMC is derived solely from the placenta, with no interference from ma ternal pituitary secretion, and is thus a new and specific placental marker .