Although there is extensive evidence for effects of prolactin (PRL) on the brain, knowledge about the PRL receptor (PRL-R) in the brain is limited. By using monoclonal antibodies raised against purified rat liver PRL-R, the distribution of PRL-R was investigated by immunohistochemistry in brains of the estrogen-treated ovariectomized (OVX+E) rat and the adult male rat. Immunohistochemistry was performed by using the avidin biotinylated horse radish peroxidase macromolecular complex method. In both male and OVX+E rats, strong immunostaining was detected in the choroid plexus of all cerebral ventricles. This immunostaining was localized predominately on epithelial cell membranes. In the OVX+E female rat, scattered immunoreactive perikarya were observed in the arcuate nucleus, periventricular hypothalamic nucleus, preoptic area, suprachiasmatic nucleus, and supraoptic nucleus of the hypothalamus. Immunostaining in hypothalamic nuclei was localized on neuronal cell bodies as well as on neuronal processes. In addition, there was extensive PRL-R immunoreactivity throughout the globus pallidus and ventral pallidum. Immunostaining in these striatal regions was not associated with neuronal cell bodies but appeared to be localized on processes or glial cells. In the male rat, less immunostaining was observed in the hypothalamus, and there was no immunostaining in the corpus striatum. No significant staining was observed in the cerebral cortex, thalamus, or hindbrain of either male or OVX+E rats. The implication of PRL-R existence in these brain regions remains to be investigated.

Prolactin is required for lobuloalveolar development in the mammary gland during pregnancy, for lactogenesis at parturition, and for the ongoing maintenance of milk secretion during lactation (Tucker, 1994). There is increasing evidence that prolactin also exerts important actions in the central nervous system (CNS) during pregnancy and lactation. In mammals, successful reproduction requires a wide range of adaptations to occur in the mother. Maternal homeostatic regulators are set at new levels, to allow the mother to cope with the metabolic, physiological and physical demands of the pregnancy. Maternal commitment to reproduction continues beyond gestation, and involves the establishment of lactation and appropriate maternal behaviour. Most of the physiological and behavioural changes that occur during pregnancy and after birth are dependent upon adaptive changes that take place in the brain of the mother, driven by the hormonal changes that occur during these periods. Multiple neuronal systems are involved and co-ordination of such a broad range of neuronal systems is well suited to an endocrine signalling mechanism. This review describes the multiple changes that occur in the neuroendocrine regulation of prolactin secretion during pregnancy and lactation that result in a prolonged state of hyperprolactinaemia, and discusses the hypothesis that this hyperprolactinaemia provides the afferent signal required by the brain to register the reproductive state, allowing the organization and coordination of a wide range of behavioural and neuroendocrine adaptations in the maternal brain.

PRL secretion in several physiological and experimental conditions, including early pregnancy, is linked to the daily photoperiod. The aim of this study was to examine the antepartum increase in PRL secretion for evidence of a circadian pattern of release, as seen during early pregnancy. During the last 3 days of pregnancy blood samples were taken six times daily by means of previously implanted jugular cannulae. Plasma PRL concentrations were then measured by RIA. PRL levels were less than 10 ng/ml in all animals on day 19 of pregnancy, but during the light period of day 20 there was an increase to an average of 30 +/- 10 ng/ml, with no evidence of a peak related to the time of day. However, in the dark period between days 20 and 21 there was a large surge of PRL secretion which reached peak levels of 356 +/- 39 ng/ml at 0500 h on day 21, then returned to 48 +/- 20 ng/ml at 1200 h, around the time of parturition. The peak always occurred at 0500 h and was not related to the time of parturition which ranged from 1000-2200 h on day 21. Bilateral ovariectomy (OVX) on day 19 advanced the time of delivery by approximately 12 h. In seven of nine animals, no surge of PRL secretion was observed during the dark period preceding parturition. Estradiol treatment after OVX on day 19 (OVX+E) advanced the time of delivery by approx 18 h. An antepartum PRL surge was present and was advanced by 24 h in all OVX+E animals, peaking at 0300 h on day 20. Progesterone treatment from day 18 to 21 in intact pregnant animals delayed parturition by approximately 18 h and prevented PRL secretion during the period of treatment. After progesterone treatment was stopped, a nocturnal surge of PRL secretion occurred, peaking at 0500 h on day 22, 24 h after the surge in normal animals. The results suggest that the increased PRL secretion during late pregnancy is linked to the daily photoperiod and is characterized by a nocturnal surge in the dark period preceding parturition. This surge is inhibited by progesterone, and it can be advanced 24 h by estradiol treatment in the absence of the ovaries.

No abstract

The regulation of energy balance requires a complex system to homeostatically maintain the adult body at a precise set point. The central nervous system, particularly the hypothalamus, plays a key role in integrating a variety of signals that can relay information about the body’s energy stores. As part of this system, numerous cytokines and hormones contribute to the regulation of food intake and energy homeostasis. Cytokines, and some hormones, are known to act through JAK-STAT intracellular signaling pathways. The hormone leptin, which plays a vital role in appetite regulation, signals through the JAK-STAT pathway, and it is through this involvement that the JAK-STAT pathway has become an established component in the mechanisms regulating food intake within the body. Emerging research, however, is now showing that this involvement of JAK-STAT is not limited to its activation by leptin. Furthermore, while the JAK-STAT pathway may simply act to transmit the anorectic signal of circulating factors, this intracellular signaling pathway may also become impaired when normal regulation of energy balance is disrupted. Thus, altered JAK-STAT signaling may contribute to the breakdown of the normal homeostatic mechanisms maintaining body weight in obesity.