Inhibitory effects of anti-prolactin receptor antibodies on prolactin binding in brain and prolactin-induced feeding behavior in ring doves.
ABSTRACT Although binding sites for prolactin (PRL) have been mapped and partially characterized in the brains of several species, there is as yet no direct evidence that the effects of intracranial PRL on brain function are receptor-mediated events. We addressed this question by testing whether antibodies generated against rat liver PRL receptors can effectively antagonize the ability of PRL to enhance feeding behavior in male ring doves (Streptopelia risoria). Both agents were administered directly to the ventromedial hypothalamic nucleus (VMN), which is an effective site of PRL action in promoting hyperphagia in this species. In the initial study, affinity-purified gamma-globulin (IgG) from the receptor antiserum preparation was tested for its ability to compete with 125I-ovine PRL for binding to receptors in rat liver, dove choroid plexus, and 6 PRL-sensitive dove brain regions using in vitro quantitative film autoradiography. Although the binding affinity of the anti-PRL receptor antibodies was at least 50 times lower in dove brain than in rat liver, a 40-50% inhibition of specifically bound 125I-ovine PRL was observed in choroid plexus and in 5 of 6 brain regions with anti-receptor IgG concentrations of 5.8 x 10(-7) M and 1.2 x 10(-6) M, using sections incubated with normal rabbit serum (NRS) IgG as a control. In a second study, anti-PRL receptor IgG or NRS IgG (2.4 micrograms) was injected unilaterally into the VMN at 45-60 min prior to VMN injection of ovine PRL (50 ng) or saline vehicle. This procedure was repeated at twice-daily intervals for 5 days. When compared to the feeding behavior of PRL-injected birds given NRS IgG, antireceptor antibody-treated animals showed a marked reduction in PRL-induced hyperphagia. The magnitude of this reduction was calculated to be approximately 50% after corrections were made for a mild hypophagia induced by the anti-receptor IgG treatment alone, as reflected in the feeding behavior of the anti-PRL receptor IgG + vehicle-treated group. These results suggest that PRL receptors in dove brain and rat liver exhibit structural similarities as well as differences and that the hyperphagia induced by intracranial injections of PRL is mediated, at least in part, by interactions with PRL receptors in the brain.
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ABSTRACT: Chronic intracerebroventricular (icv) infusion of prolactin (PRL) into the cerebral ventricles and mimicking central hyperprolactinemia in lactation has recently been shown to reduce anxiety and neuronal as well as neuroendocrine responses to acute stressor exposure. Here, we studied the effects of icv PRL on the activity of the oxytocin (OXT) and arginine vasopressin (AVP) systems of virgin female, ovariectomized, estradiol-substituted Wistar rats. Ovine PRL was delivered via osmotic minipumps at 0.01, 0.1 or 1 microg/h for 5 days. Under basal conditions, both plasma OXT and AVP concentrations were increased after chronic PRL treatment (1 microg/h). At hypothalamic level, this was accompanied by an increased c-fos and OXT mRNA expression within the supraoptic nucleus, the main source of plasma OXT, whereas AVP mRNA levels remained unchanged. No effect of PRL on c-fos or on nonapeptide mRNA expression was found in the hypothalamic paraventricular nucleus. Moreover, chronic PRL abolished the rise in plasma OXT induced by acute exposure to 30 min restraint stress in vehicle-treated rats. However, restraint stress did not significantly alter OXT or AVP mRNA expression in the hypothalamus of either vehicle- or PRL-treated animals. From these results we conclude that brain hyperprolactinemia alters the synthetic activity of OXT neurons and the secretory performance of OXT and AVP neurons within the hypothalamus, resulting in elevated plasma concentrations of both hormones under basal conditions. These changes are comparable to adaptations seen in the female peripartum period.Neuroendocrinology 07/2009; 90(3):315-22. · 3.54 Impact Factor
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ABSTRACT: Primate communication systems are complex and utilize manual gestures and vocalization for the transfer of information. The relationship between these two communicatory media has become increasingly interdependent in apes as specific cerebral regions have gradually assumed a governing role in cognitive communication processes. Over the course of primate evolution, subcortically processed monkey vocalizations have become largely corticalized and lateralized to the left hemisphere in humans. The emergence of handedness has shifted cortical control over manual gestures to the left hemisphere and established a cerebral specialization subserving gesture and vocalization in higher primates.Handbook of Behavioral Neuroscience 01/2009; 19:469-476.
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ABSTRACT: Prolactin (PRL) has been shown to promote maternal behaviour, and to regulate neuroendocrine and emotional stress responses. These effects appear more important in the peripartum period, when the brain PRL system is highly activated. Here, we studied the mechanisms that underlie the anti-stress effects of PRL. Ovariectomized, estradiol-substituted Wistar rats were implanted with an intracerebroventricular cannula and treated with ovine PRL (0.01, 0.1 or 1 microg/h; 5 days via osmotic minipumps) or vehicle, and their responses to acute restraint stress was assessed. Chronic PRL treatment exerted an anxiolytic effect on the elevated plus-maze, and attenuated the acute restraint-induced rise in plasma adrenocorticotropin, corticosterone and noradrenaline. At the neuronal level, in situ hybridization revealed PRL effects on the expression patterns of the immediate-early gene c-fos and corticotropin-releasing factor (CRF). Under basal conditions, PRL significantly reduced c-fos mRNA expression within the central amygdala. In response to restraint, the expression of both c-fos mRNA and protein and of CRF mRNA was decreased in the parvocellular part of the paraventricular nucleus (PVN) of PRL-treated compared with vehicle-treated animals. In conclusion, our data demonstrate that chronic elevation of PRL levels within the brain results in reduced neuronal activation within the hypothalamus, specifically within the PVN, in response to an acute stressor. Thus, PRL acting at various relevant brain regions exerts profound anxiolytic and anti-stress effects, and is likely to contribute to the attenuated stress responsiveness found in the peripartum period, when brain PRL levels are physiologically upregulated.European Journal of Neuroscience 04/2007; 25(6):1804-14. · 3.75 Impact Factor