Prolactin/Leptin Interactions in the Control of Food Intake in Rats

Abstract

Recent evidence suggests that the peptide hormone prolactin (PRL) modulates energy balance through a number of mechanisms, including acting in the brain to increase food intake. In the current studies, we first demonstrated that chronic infusions of PRL into the lateral ventricles increased food intake in cycling rats without disrupting estrous cyclicity. In subsequent experiments the hypothesis that at least part of PRL's ability to increase food intake resulted from PRL-induced leptin resistance was tested. Female rats given chronic infusions of PRL (5 microg/h) into the cerebral ventricles for 10 d did not show a reduction in food intake or body weight after a central injection of 4 microg murine leptin, whereas the expected reduction in both of these parameters was seen in vehicle-infused rats. Leptin injections were without effect on these parameters, whether they were administered to free feeding PRL-infused rats or after 24-h food deprivation. This lack of a behavioral response to leptin was accompanied by an attenuation in Fos induction and phosphorylation of signal transducer and activator of transcription 3 after leptin administration in PRL-infused rats in both the ventromedial hypothalamus and paraventricular hypothalamic nucleus.

Negative correlation between milk production and brown adipose tissue gene expression in lactating mice

“…However, the lack of a BAT-independent correlation between prolactin and milk production (Fig.5) contradicts the accumulated evidence that circulating prolactin re-enters the brain, interacts with distinct populations of hypothalamic neurons that express prolactin receptors (Grattan and Kokay, 2008) and acts in female rats to induce and maintain hyperphagia (Woodside, 2007). Some of these prolactin-responsive neurons co-express leptin receptors, suggesting that prolactin and leptin in rats may act together to regulate food intake (Naef and Woodside, 2007). The discrepancy between our results and the previous research may be due to either differences between animal models (mice versus rats) or differences in the blood sampling protocols.…”

“…Circulating levels of prolactin during lactation are typically high and depend on the intensity and duration of suckling (Mattheij et al, 1979;Chan and Swaminathan, 1990). Both suppression of leptin and induction of prolactin have been suggested to contribute to lactational hyperphagia, facilitating milk production (Crowley et al, 2004;Naef and Woodside, 2007;Woodside, 2007;Smith et al, 2010). Importantly, both of these hormones have also been demonstrated to modify the gene and protein expression of UCP1 in BAT (Chan and Swaminathan, 1990;Pearce et al, 2003;Cannon and Nedergaard, 2004;Xiao et al, 2004;Cui et al, 2011).…”

“…We also measure circulating levels of leptin and prolactin, both of which have received considerable attention as endocrine mediators that may coordinate the lactational changes in BAT activity and food intake to facilitate milk production (Cannon and Nedergaard, 2004;Crowley et al, 2004;Naef and Woodside, 2007;Woodside, 2007;Smith et al, 2010).…”

Interactions between prolactin and kisspeptin to control reproduction

“…Several studies also indicate that prolactin or placental lactogens contribute to the metabolic changes typically observed during pregnancy, such as the increase in food intake and adiposity. These studies showed that central prolactin infusions induce a leptin resistance state that changes the metabolism towards a positive energy balance (35,36). Indeed, several populations of leptin receptorexpressing neurons in mice are directly responsive to prolactin (37).…”

20 YEARS OF LEPTIN: Role of leptin in human reproductive disorders

“…In pregnant rodents, central administration of leptin results in reduced food intake until mid-pregnancy when central resistance to leptin develops (Johnstone & Higuchi 2001, Mistry & Romsos 2002. In addition to an increase in plasma leptin-binding activity seen in pregnant rats (Seeber et al 2002), progesterone, prolactin, and placental lactogen may also contribute to leptin resistance (Grueso et al 2001, Naef & Woodside 2007, Brunton & Russell 2008. The development of hyperleptinemia and leptin resistance during pregnancy has been proposed to be a compensatory mechanism to allow for increased appetite and food intake to meet the energy needs of the developing fetus (Brunton & Russell 2008).…”