Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperprolactinemia and hyperleptinemia occur during gestation and lactation with marked hyperphagia associated with leptin resistance. Prolactin (PRL) induces the expression of orexigenic neuropeptide Y (NPY) through the activation of JAK-2/STAT-3 signaling pathway in hypothalamic paraventricular nucleus (PVN) leading to hyperphagia. PRL may also act through the inhibition of anorexigenic effect of leptin via induction of suppressor of cytokine signaling 3 (SOCS-3). This paper aimed to co-localize PRL (PRL-R) and leptin (ObRb) receptors in the hypothalamus of female rats and investigate the possible cross-desensitization between PRL-R and ObRb. We showed that: 1) PRL-R and ObRb are expressed in the PVN and co-localized in the same neurons; 2) in lactating females leptin failed to activate JAK-2/STAT-3 signaling pathway; 3) in Chinese Hamster Ovary (CHO) stably co-expressing PRL-R and ObRb, overexposure to PRL did not affect leptin signaling but totally abolished PRL-dependent STAT-5 phosphorylation. The overexposure to leptin produces similar results with strong alteration of leptin-dependent STAT-3 phosphorylation, whereas PRL-dependent STAT-5 was not affected; and 4) CHO-ObRb/PRL-R cells overexposure to leptin or PRL induces the expression of negative regulators SOCS-3 and PTP-1B. Thus, we conclude that these negative regulators affect specifically the inducer signaling pathway; for instance, SOCS-3 induced by PRL will affect PRL-R signaling but not ObRb signaling and vice versa. Finally, the lack of cross-desensitization between PURL-R and ObRb suggests that hyperphagia observed during gestation and lactation may be attributed to a direct effect of PRL on NPYexpression, and is most likely exacerbated by the physiological leptin resistance state.
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PMID:Lack of cross-desensitization between leptin and prolactin signaling pathways despite the induction of suppressor of cytokine signaling 3 and PTP-1B. 1795 45

Hyperprolactinemia occurs during gestation and lactation with marked hyperphagia associated with leptin resistance. Prolactin (PRL) induces the expression of orexigenic neuropeptide Y (NPY) in hypothalamic dorsomedial nucleus (DMH) leading to hyperphagia. Along this line prolactin receptor deficient (PRLR-/-) mice are resistant to obesity under high fat diet due to increased energy expenditure. As these mice have an altered food intake, our objective was to test whether leptin is responsible for these characteristics. PRLR-/- male mice and control littermates were injected subcutaneously every other day with 12 mg/kg pegylated superactive mouse leptin antagonist (PEG-SMLA) for 3 weeks. We tested the effect of PEG-SMLA on body weight, food intake and metabolic parameters. The antagonist led to a rapid increase in body weight (20%) but increased adipose mass in PEG-SMLA treated mice was less pronounced in PRLR-/- than in WT mice. Food intake of PEG-SMLA-injected animals increased during the first week period of the experiment but then declined to a similar level of the control animals during the second week. Interestingly, PRLR-/- mice were found to have the same bone volume than those of control mice although PEG-SMLA increased bone mass by 7% in both strains. In addition, PEG-SMLA led to insulin resistance and glucose intolerance as well as an altered lipid profile in treated mice. Altogether, these results suggest that PRLR-/- mice respond to leptin antagonist similarly to the control mice, indicating no interaction between the actions of the two hormones.
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PMID:Effects of high affinity leptin antagonist on prolactin receptor deficient male mouse. 2466 51

Prolactin (PRL) released from lactotrophs of the anterior pituitary gland in response to the suckling by the offspring is the major hormonal signal responsible for stimulation of milk synthesis in the mammary glands. PRL secretion is under chronic inhibition exerted by dopamine (DA), which is released from neurons of the arcuate nucleus of the hypothalamus into the hypophyseal portal vasculature. Suckling by the young activates ascending systems that decrease the release of DA from this system, resulting in enhanced responsiveness to one or more PRL-releasing hormones, such as thyrotropin-releasing hormone. The neuropeptide oxytocin (OT), synthesized in magnocellular neurons of the hypothalamic supraoptic, paraventricular, and several accessory nuclei, is responsible for contracting the myoepithelial cells of the mammary gland to produce milk ejection. Electrophysiological recordings demonstrate that shortly before each milk ejection, the entire neurosecretory OT population fires a synchronized burst of action potentials (the milk ejection burst), resulting in release of OT from nerve terminals in the neurohypophysis. Both of these neuroendocrine systems undergo alterations in late gestation that prepare them for the secretory demands of lactation, and that reduce their responsiveness to stimuli other than suckling, especially physical stressors. The demands of milk synthesis and release produce a condition of negative energy balance in the suckled mother, and, in laboratory rodents, are accompanied by a dramatic hyperphagia. The reduction in secretion of the adipocyte hormone, leptin, a hallmark of negative energy balance, may be an important endocrine signal to hypothalamic systems that integrate lactation-associated food intake with neuroendocrine systems.
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PMID:Neuroendocrine regulation of lactation and milk production. 2558 71

Prolactin and placental lactogens control mammary development and lactation as well as play an important role in maternal behaviors. However, the molecular mechanisms in the brain responsible for this regulation remain largely unknown. Therefore, the present study investigated whether Signal Transducer and Activator of Transcription 5 (STAT5) signaling in the brain, the key transcriptional factor recruited by prolactin receptor and other hormones, is required for postpartum maternal behavior, maintenance of lactation and offspring growth. Neuronal ablation of STAT5 impaired the control of prolactin secretion and reduced the hypothalamic expression of suppressors of cytokine signaling (i.e., SOCS3 and CISH). In addition, neuronal STAT5 deletion attenuated the hyperphagia commonly observed during lactation by decreasing the hypothalamic expression of orexigenic neurotransmitters such as the neuropeptide Y and agouti-related protein. The lower food intake of lactating neuron-specific STAT5 knockout females resulted in reduced milk production and offspring growth. Unexpectedly, postpartum maternal behavior expression was not impaired in neuron-specific STAT5 knockout females. On the contrary, the latency to retrieve and group the pups into the nest was reduced in mutant dams. Finally, we demonstrated that approximately 30% of recorded neurons in the medial preoptic area were acutely depolarized by prolactin suggesting that fast STAT5-independent signaling pathways may be involved in the regulation of maternal behaviors. Overall, our results revealed important information about the molecular mechanisms recruited by hormones to orchestrate the activation of neural circuitries engaged in the induction of maternal care.
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PMID:Neuronal STAT5 signaling is required for maintaining lactation but not for postpartum maternal behaviors in mice. 2589 18


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