Hepatic Prolactin Receptor Gene Expression Increases in the Sheep Fetus Before Birth and After Cortisol Infusion

We have investigated the effect of increasing gestational age and cortisol on prolactin receptor (PRLR) gene expression in the fetal sheep liver during late gestation. RNA was extracted from the liver of sheep fetuses between 90 and 144 days (d) gestation (n = 18) and after intrafetal infusion of either cortisol (2–2.5 mg cortisol i.v./24 h; n = 6) or saline (n = 6) between 109 and 116 d gestation. A ribonuclease protection assay for the mRNAs encoding the long (PRLR1) and short (PRLR2) forms of the PRLR was developed using an antisense RNA probe complementary to ovine PRLR2. There was a significant increase (p < 0.05) in the relative levels of liver PRLR1:GAPDH mRNA and PRLR2:GAPDH mRNA levels in fetal sheep between 90 and 144 d gestation (PRLR1 mRNA: 90–95 d 0.6 ± 0.1, 131–133 d 1.2 ± 0.2, 141–144 d 3.6 ± 0.5; PRLR2 mRNA: 90–95 d 0.7 ± 0.1; 131–133 d 1.4 ± 0.2, 141–144 d 3.0 ± 0.4). The relative levels of liver PRLR1 and PRLR2:GAPDH mRNA levels were higher (p < 0.05) after cortisol administration (1.7 ± 0.3 and 0.9 ± 0.1 respectively) when compared with the saline infused group (0.7 ± 0.1 and 0.5 ± 0.1 respectively). We have demonstrated therefore that there is an increase in the levels of the mRNA encoding PRLR1 and PRLR2 in the fetal sheep liver during late gestation and that physiological increases in fetal cortisol stimulate PRLR1 and PRLR2 expression in the liver of the sheep fetus. These data suggest that fetal PRL may play a role in the growth and maturation of the fetal liver which occurs before birth.Ian D. Phillips, Russell V. Anthony, Timothy G. Butler, Jacob T. Ross and I. Caroline McMille