Prolactin receptor knockdown in the rat paraventricular nucleus by a morpholino-antisense oligonucleotide causes hypocalcemia and stress gastric erosion

Under acute stress conditions in the rat, there is rapid and transient increase in circulating prolactin (PRL). This leads to an elevated expression of the long form of PRLR (PRLR-L) first in the hypothalamus and the choroid plexus. This increase in PRL is involved in the inhibition of stress-induced hypocalcemia and gastric erosion. In this study, we used rat PRL and a PRLR morpholino-antisense oligonucleotide to elucidate the mechanism by which hypothalamic PRLR mediates the inhibition of restraint stress in water (RSW)-induced hypocalcemia and gastric erosion. We found that this effect is largely mediated by PRLRs in the paraventricular nucleus (PVN), medial preoptic nucleus, and ventromedial hypothalamus. We further show that, when measured after 7 h of RSW, microinjection of the PRLR antisense oligonucleotide into these areas down-regulates RSW-enhanced expression of PRLR-L protein in the PVN, and increases plasma level of PRL but does not affect plasma level of other hormone, growth hormone. Furthermore, our experiments demonstrated that, under non-stress conditions, knockdown of the PRLR in the PVN significantly lowers circulating Ca(2+) levels but does not affect gastric erosion. These results suggest that PRL acting on the PRLR-L in the PVN is one of the critical pathways for regulating circulating Ca(2+) levels under both acute stress and non-stress conditions.