Restriction of fetal growth has a differential impact on fetal prolactin and prolactin receptor mRNA expression

Prolactin is present in the fetal circulation and prolactin receptors are expressed in a wide range of fetal tissues. The factors which regulate the synthesis and secretion of prolactin, and the expression of its receptors before birth, are poorly understood. We have investigated whether experimental restriction of placental growth in the sheep has an impact on the prolactin axis in the growth restricted fetus. The majority of uterine endometrial caruncles were removed before pregnancy in 10 ewes (placental restriction; PR group). Placental, fetal liver and kidney weights were reduced in the PR compared to the control group (n =10). The ratio of fetal prolactin mRNA:18S rRNA was significantly lower (P <0.01) in the PR group (1.83 +/- 0.45, n = 6) than in the control group (4.11 +/- 0.54, n = 6), The ratio of prolactin mRNA: 18S rRNA in the fetal pituitary was positively correlated with fetal and with placental weight. Using stepwise linear regression, it was determined that the level of fetal prolactin mRNA:18S rRNA expression was best described (as judged by the maximum adjusted R-2) by prolactin mRNA, 18 S rRNA = -3.0378 + 0.17 PO2+2.772 glucose (adjusted R-2 = 0.765, F = 17.53, P < 0.001), Fetal plasma prolactin concentrations were significantly reduced (P <0.05) in the PR group compared to control animals between 109 and 141 days gestation. Fetal prolactin receptor (PRLR) mRNA transcripts encoding long (PRLR1) and short forms (PRLR2) of PRLR were present in the liver and kidney of animals in the PR and control groups at 140-141 days gestation. PR did not alter the levels of PRLR1 or PRLR2 mRNA in the fetal liver or kidney. The suppression of the synthesis and secretion of prolactin in the growth restricted fetus may limit the action of prolactin on the growth and metabolism of key fetal organs during suboptimal intrauterine conditions.