Expression of the long form of the prolactin receptor in magnocellular oxytocin neurons is associated with specific prolactin regulation of oxytocin neurons

Abstract

neurons of the supraoptic (SON) and paraventricular nuclei (PVN) show considerable plasticity during pregnancy and lactation. Prolactin receptors (PRL-R) have been identified in both these nuclei. The aim of this study was to investigate the cell type(s) expressing mRNA for the long form of prolactin receptor (PRL-R L) and to determine whether patterns of expression change during pregnancy and lactation. In addition, we examined effects of prolactin on excitability of oxytocin and vasopressin neurons. Sections from brains of nonpregnant, pregnant, and lactating rats were hybridized with an 35 S-labeled probe to label PRL-RL mRNA together with digoxigenin-labeled probes to detect either oxytocin or vasopressin mRNA. In the SON, PRL-R L mRNA was predominantly colocalized with oxytocin mRNA, with over 80% of oxytocin neurons positive for PRL-R L mRNA. Very few (Ͻ10%) vasopressin neurons expressed PRL-R L mRNA. In the PVN, PRL-RL mRNA was also predominantly found in oxytocin neurons, and the proportion of PRL-R L-positive oxytocin neurons increased significantly during pregnancy and lactation. As in the SON, relatively few vasopressin cells contained PRL-R L mRNA. For in vivo electrophysiology, nonpregnant rats were anesthetized, and then extracellular single neuron activity was recorded in identified oxytocin and vasopressin neurons. After a period of baseline recording, the effect of prolactin (1 g icv) on firing rate was examined. Prolactin treatment of nonpregnant rats induced a significant decrease in firing rates of oxytocin neurons. There was no effect of prolactin on the activity of vasopressin neurons. Together, these data provide strong evidence that prolactin directly and specifically regulates activity of oxytocin neurons. pregnancy; lactation; magnocellular neurons; in situ hybridization IN ADDITION TO ITS CRITICAL actions in mammary gland function during pregnancy and lactation, the anterior pituitary hormone prolactin exerts important actions within the brain. Prolactin is thought to gain access to the brain through a carrier-mediated transport system (74), likely involving prolactin receptors in the choroid plexus (51, 64). Prolactin receptor (PRL-R) mRNA (3,4,11,45) and protein (13, 46) have been identified in many hypothalamic nuclei. Interestingly, PRL-R expression in the choroid plexus is markedly increased during pregnancy and lactation (2), suggesting increased access of prolactin to brain structures during these conditions. Similarly, levels of PRL-R protein in the hypothalamus appear to increase during lactation compared with nonpregnant rats (47-49). These observations suggest that prolactin may be a major regulator of hypothalamic function, particularly during pregnancy and lactation, when prolactin levels are elevated (22,23).Within the hypothalamus, the neurons that undergo one of the most dramatic changes during pregnancy and lactation are the magnocellular neurons of the supraoptic (SON) and paraventricular (PVN) nuclei (26). PRL-R mRNA has been identified in both of these nuclei (3, 4...

Tissue-specific regulation of porcine prolactin receptor expression by estrogen, progesterone, and prolactin

“…Levels of pPRLR-LF mRNA in tissues from Sal-treated animals were set to 100%. (Kokay et al 2006). PRL regulates its own secretion at the level of the hypothalamus, where the wide influence of PRL on brain functions is thought to be required for neurobiological adaptations during preparation for pregnancy and lactation .…”

Prolactin secretion patterns: basic mechanisms and clinical implications for reproduction

“…Up to now, only controversial data are available regarding the PRL effect on oxytocin containing periventricular neurons (Ghosh & Sladek 1995, Kokay et al 2006, White & Samson 2006. The mathematical model is based on the assumption that PRL exerts a stimulatory influence on oxytocin containing PVN cells.…”

Prolactin Regulates Tuberoinfundibular Dopamine Neuron Discharge Pattern: Novel Feedback Control Mechanisms in the Lactotrophic Axis

“…Compared with slow transcriptional and biosynthetic changes, the presumably more rapid electrophysiological effects of Prl on TIDA neurons have yet to be described. Indeed, although a few extracellular recordings have been published (Townsend et al, 2005;Kokay et al, 2006), there is to date no description of Prl actions on active or passive membrane properties in any neuronal system. This lack of information is particularly surprising given the pleiotropic effects of this hormone and the numerous expression sites of Prl receptors in the CNS (Chiu and Wise, 1994;Pi and Grattan, 1998), including TIDA neurons (Kokay and Grattan, 2005).…”