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

Abstract

ACTH-producing non-pituitary tumours are often associated with altered precursor processing, particularly in the most aggressive ones. Since placental tissue is characterized by its ability to express the proopiomelanocortin (POMC) gene and rapid cellular proliferation, we examined whether intact POMC could be released physiologically during human gestation. 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. We measured plasma POMC levels with a specific immunoradiometric 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. Reverse transcription-PCR detected full length, pituitary-like, POMC mRNA in human placenta. Plasma POMC was undetectable (< 60 U/ml) in 23 normal subjects. In normal monofetal pregnancies, POMC became detectable in most women by the third 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 and 308 +/- 210 between 36 weeks and parturition. Plasma POMC was significantly higher in multiple pregnancies with very high levels in three triplet-bearing mothers: 671, 941, and 1731 U/ml at 31, 33 and 32 weeks, respectively. POMC levels felt quickly in post partum, becoming undetectable in five of 13 women on day 1, seven of eight on day 2 and five of six on day 3. Plasma POMC displayed no diurnal variation, was not suppressed by glucocorticoid administration and did not correlate with plasma ACTH or cortisol. In contrast, plasma POMC positively correlated with plasma CRH. Pregnancy is the only condition in which POMC is produced and released physiologically, similar in some respects to the ectopic ACTH syndrome. POMC is derived solely from the placenta, with no interference from maternal pituitary secretion, and is thus a new and specific placental marker.