Ontogenesis of prolactin receptors in the human fetus: roles in fetal development.

The lactogenic hormones prolactin (PRL) and placental lactogen circulate in human fetal plasma during mid and late gestation. To explore potential roles for the lactogens in fetal development, we examined the cellular distribution and changes in expression of PRL receptors (PRLRs) during ontogeny, and the metabolic effects of PRL signalling and PRLR dysregulation. PRLRs are expressed in diverse tissues of the human fetus by 7.5 weeks of gestation. In fetal bone, adrenal gland and lung, the receptor is expressed first in mesenchymal cells and subsequently in maturing chondrocytes, adrenocortical cells and bronchiolar epithelial cells. That the lactogens play roles in fetal chondrogenesis is suggested by studies in PRLR-deficient mice, which show a delayed ossification of the calvarium. In the central nervous system, the PRLR is detected initially in periventricular neuroepithelium and later in mature neurons of the hypothalamus and olfactory bulb. Finally, in the pancreas, the PRLR is detected first in exocrine tissue and ductal epithelium. Later in gestation and in the postnatal period, PRLRs predominate in pancreatic beta-cells. The lactogens regulate beta-cell proliferation and insulin production in pancreatic islets, and the insulin secretory response to glucose is blunted in PRLR-deficient mice. These observations suggest roles for the lactogens in pancreatic development and function during pregnancy and postnatal life.