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 γ-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 autoradiogra-phy. 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 × 10^-7M and 1.2 × 10^-6M, 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 µg) 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, anti-receptor 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.

Anxiolytic and Anti-Stress Effects of Brain Prolactin: Improved Efficacy of Antisense Targeting of the Prolactin Receptor by Molecular Modeling

“…2 B). Several studies addressing behavioral effects of PRL have also demonstrated PRL actions in both genders (Li et al, 1995;Heil, 1999). PRL-R have been mapped in the brain of both female (Crumeyrolle-Arias et al, 1993;Chiu and Wise, 1994;Bakowska and Morrell, 1997;Grattan, 1998, 1999) and male rats (Muccioli et al, 1991;Roky et al, 1996;Pi and Grattan, 1998).…”

“…On the basis of different techniques, this neuropeptide has been shown to participate in the regulation of maternal behavior (Bridges et al, 1990;Lucas et al, 1998), grooming (Drago et al, 1983), and food intake in mammalian (Noel and Woodside, 1993) and nonmammalian species (Li et al, 1995). A possible involvement of PRL in stress response mechanisms is suggested by the findings that (1) PRL is released into the blood from pituitary lactotroph cells in response to exposure to different stressors (Neill, 1970;Seggie and Brown, 1975), (2) chronic stress induced the expression of the long form of the PRL receptors (PRL-R) in choroid plexus cells (Fujikawa et al, 1995), and (3) administration of PRL into the cerebral ventricles prevented the stressinduced formation of gastric ulcers and showed antidepressant effects during forced swimming (Drago et al, 1985(Drago et al, , 1990.…”

Effect of Suckling on Prolactin Receptor Immunoreactivity in the Hypothalamus of the Rat

“…Therefore, the increased expression of PRL receptor in the VMH was probably not initiated during pregnancy but caused by suckling during lactation. PRL receptors in the VMH have been demonstrated to be involved in control of feeding behavior [36]. Markedly increased food intake is characteristic for lactating mothers to meet nutritional demands.…”

Increased expression of both short and long forms of prolactin receptor mRNA in hypothalamic nuclei of lactating rats

“…Nonetheless, some suggestions can be made. It is suggested that the VMH regulates feeding behaviour (Li et al 1995). Since experimental hyperprolactinaemia produces an increase in food intake in female rats (Sauve & Woodside 1996), PRL-R in the VMH may be involved in the increased feeding behaviour specific to lactating rats.…”