The regulation of prolactin receptor messenger ribonucleic acid levels in the sheep liver before birth: relative roles of the fetal hypothalamus, cortisol, and the external photoperiod

Abstract

We have investigated the separate actions of hypothalamo-pituitary disconnection (HPD), with or without cortisol administration, and changes in the external photoperiod on the regulation of the levels of messenger RNA (mRNA) encoding long (PRLR1) and short (PRLR2) forms of PRL receptor in the liver of the fetal lamb. In pregnant Merino ewes (n520), the hypothalamus and pituitary were surgically disconnected in 13 fetuses (HPD group), and fetal vascular catheters were implanted in the HPD group and in an additional 7 fetuses (intact 1 saline group) between 104–120 days gestation (d). Fetal sheep in the HPD group were infused with either cortisol (3.5 mg/4.8 ml saline/24 h; HPD 1 F; n 5 5) or saline for 5 days between 134–141 d, and saline was also infused in the intact group within the same gestational age range. A second group of pregnant ewes (n512) was kept in a 12-h light, 12-h dark cycle from 70 d until implantation of fetal vascular catheters between 106–120 d, after which ewes were allocated to either a long photoperiod (16 h of light, 8 h of darkness; LL group; n 5 6) or a short photoperiod (8 h of light, 16 h of darkness; SL group; n 5 6) regimen. Circulating cortisol concentrations were higher (P , 0.05) in the intact fetal sheep (18.7 6 3.8 nmol/liter) than in the HPD 1 saline group (1.5 6 0.6 nmol/liter), and were further increased (P , 0.05) in the HPD 1 cortisol group (97.4 6 23.7 nmol/ liter). Fetal PRL concentrations were lower (P , 0.05) in the HPD 1 saline (10.6 6 4.3 ng/ml) and HPD 6 cortisol (5.6 6 2 ng/ml) groups compared with those in the intact group (38.9 6 6.8 ng/ml). The levels of hepatic PRLR mRNA were higher (P , 0.05) in the intact (PRLR1, 27.4 6 6.1; PRLR2, 17.7 6 2.5) and HPD 1 cortisol (PRLR1, 23.4 6 0.4; PRLR2, 15.3 6 3.0) groups than in the HPD 1 saline group (PRLR1, 10.661.8; PRLR2, 8.961.8) at 140/141 d. The mean plasma PRL concentration in the LL group (70 6 9 ng/ml) was higher (P , 0.05) than that in the SL group (34 6 15 ng/ml), whereas the levels of hepatic PRLR1 mRNA (LL group, 4.6 6 0.9; SL group, 4.3 6 0.8) and PRLR2 mRNA (LL group, 3.4 6 0.4; SL group, 3.0 6 0.5) at 140–141 d were not different. These data indicate that cortisol acts directly or indirectly to maintain hepatic PRLR mRNA levels in the sheep fetus during late pregnancy. In contrast, changes in the external photoperiod and circulating PRL concentrations in the sheep fetus do not directly alter PRLR expression in the fetal liver. These studies provide further insight into the role that the PRL axis may play in the transduction of signals about the external environment to the fetus as it prepares for the transition to extrauterine life.