ICV galanin-like peptide stimulates non-contact erections but not touch-based erections in adult, sexually experienced male rats.

Galanin-like peptide (GALP) is a neuropeptide transcribed only within the arcuate nucleus of the hypothalamus and is thought to be a mediator between energetics and reproductive function. Intracerebroventricular (ICV) injection of GALP is known to have effects on feeding, and to significantly increase gonadotropin releasing hormone- (GnRH-) mediated luteinizing hormone (LH) secretion. Furthermore, ICV GALP is known to stimulate fos production in the medial pre-optic area (mPOA) and to a lesser extent, the paraventricular nucleus (PVN). ICV injection of 5.0nmol GALP profoundly stimulates male rat sexual behavior. It is not known if GALP's effects on sex behavior are due to an increase in appetitive or mechanical (erectile) aspects of male sexual behavior. To determine this, sexually experienced male rats were cannulated in the lateral ventricle and injected with 5.0nmol GALP or vehicle. Immediately after injections, male rats were placed in an arena connected to a second arena via a tube with a fan. The second arena contained a steroid-primed female and her bedding. The male rat had olfactory but not visual or tactile contact with the female. We analyzed the amount of time the male rats spent investigating the air intake and the number of non-contact erections (NCEs) in a 30minute test. ICV GALP significantly (p<0.05) increased both the amount of time of olfactory investigations and NCEs compared to vehicle. In a second set of animals, we tested if ICV GALP could stimulate touch-based erections. GALP had no significant effect on touch-based erections compared to vehicle. These data suggest that GALP's activation of fos within the mPOA is indicative of its action to stimulate the appetitive aspects of male sexual behavior.

Injections of Galanin-Like Peptide directly into the nucleus of the tractus solitarius (NTS) reduces food intake and body weight but increases metabolic rate and plasma leptin.

Galanin-Like Peptide (GALP) is a hypothalamic neuromediator of metabolism and reproduction. GALP is known to stimulate reproduction and alter food intake and body weight in multiple species. The regulation of body weight involves control of both energy intake and energy expenditure. Since GALP is known to alter food intake - possibly via the autonomic nervous system - we first hypothesized that GALP would increase metabolic rate. First, male Sprague-Dawley rats were implanted with intracerebroventricular (ICV) cannulae and abdominal radiotelemetry temperature transmitters. Following ICV injection with either 5nmol GALP or vehicle, the oxygen consumption of each rat was monitored for 8h. Food intake, core temperature, and general motor activity were monitored for 24h. GALP significantly increased oxygen consumption, an indirect estimator of metabolic rate, without having any significant effect on motor activity. Compared to controls, GALP increased core body temperature during the photophase and reduced food intake over the 24h period following injection. ICV GALP also increased plasma levels of luteinizing hormone (LH). A second group of male Sprague-Dawley rats were implanted with abdominal transmitters and given injections of GALP directly into the nucleus of the tractus solitarius (NTS). These injections resulted in a significant reduction in food intake, and a significant increase in both oxygen consumption and core body temperature compared to vehicle injections. Direct injections of GALP into the NTS compared to vehicle also resulted in a significant increase in plasma leptin levels, but not LH levels. GALP appears to increase energy expenditure in addition to decreasing energy input by actions within the NTS and thus may play an important role in the hypothalamic regulation of body weight.

Gonadotropin-inhibitory hormone is a hypothalamic peptide that provides a molecular switch between reproduction and feeding.

OBJECTIVE: Gonadotropin-inhibitory hormone (GnIH)-3 is a neuropeptide that plays a major role in the regulation of reproduction and feeding in mammals. MATERIALS AND METHODS: We measured endocrine and behavioural parameters of reproduction in sheep, and sexual behaviour in sheep, mice and cynomolgus monkeys. In addition, GnIH gene expression (in situ hybridization) was examined in ewes, and effects of GnIH-3 on food intake and energy expenditure were measured in various species. GnIH-3 was infused (i.v.) into ewes after an i.m. injection of estradiol benzoate to determine whether the peptide blocks the surge in luteinizing hormone (LH) secretion. RESULTS: GnIH gene expression was reduced in the preovulatory period in ewes. Infusion (i.v.) of GnIH-3 blocked the estrogen-induced LH surge (in ewes). Intracerebroventricular infusion had no effect on female or male sexual behaviour in each of the three species, but increased food intake. There were no effects on energy expenditure in sheep or rats. GnIH increased fos protein (immunohistochemistry) was seen in orexigenic neurons (in sheep and rats), but also in anorexigenic neurons (in sheep). CONCLUSIONS: GnIH-3 reduces reproductive hormone levels and increases food intake in mammals without reducing energy expenditure. There is minimal effect on reproductive behaviour. The dual effect on reproduction and feeding suggests that GnIH-3 provides a molecular switch between these two functions. Blockade of the positive feedback effect of estrogen with parenteral infusion indicates that this peptide may have utility as a blocker of reproductive function in mammals.

Galanin-like peptide (GALP) is a hypothalamic regulator of energy homeostasis and reproduction.

Galanin-like peptide (GALP) was discovered in 1999 in the porcine hypothalamus and was found to be a 60 amino acid neuropeptide. GALP shares sequence homology to galanin (1-13) in position 9-21 and can bind to, as well as activate, the three galanin receptor subtypes (GalR1-3). GALP-expressing cells are limited, and are mainly found in the arcuate nucleus of the hypothalamus (ARC) and the posterior pituitary. GALP-positive neurons in the ARC project to several brain regions where they appear to make contact with multiple neuromodulators. These neuromodulators are involved in the regulation of energy homeostasis and reproduction, anatomical evidence that suggests a role for GALP in these physiological functions. In support of this idea, GALP gene expression is regulated by several factors that reflect metabolic state including the metabolic hormones leptin and insulin, thyroid hormones, and blood glucose. Considerable evidence now exists to support the hypothesis that GALP has a role in the regulation of energy homeostasis and reproduction; and, that GALP's role may be independent of the known galanin receptors. In this review, we (1) provide an overview of the distribution of GALP, and discuss the potential relationship between GALP and other neuromodulators of energy homeostasis and reproduction, (2) discuss the metabolic factors that regulate GALP expression, (3) review the evidence for the role of GALP in energy homeostasis and reproduction, (4) discuss the potential downstream mediators and mechanisms underlying GALP's effects, and (5) discuss the possibility that GALP may mediate its effects via an as yet unidentified GALP-specific receptor.

Rat RFRP-3 alters hypothalamic GHRH expression and growth hormone secretion but does not affect KiSS-1 gene expression or the onset of puberty in male rats.

BACKGROUND/AIMS: RFRP-3 is a recently described neuropeptide that influences a variety of physiologic factors, including the inhibition of gonadotropin secretion and reproductive behaviors. We hypothesized that endogenous RFRP-3 could function to inhibit the onset of puberty in young male rats. METHODS: To test this hypothesis, we first placed cannulas into the third ventricle of 24-day-old male rat pups. The cannulas were attached to osmotic minipumps that infused antisense oligonucleotides (ODNs) against RFRP-3. Second, cannulas were placed in the ventricle of 35-day-old pups and infused with RFRP-3, NPFF (putatively, an alternative transcript of the RFRP gene), or vehicle. RESULTS: No treatment altered the onset of puberty compared to controls. RFRP-3 ODN rats had significantly larger testes compared to control rats. Similarly, the RFRP-3 ODN-treated rats had a significant increase in plasma LH, but not FSH, compared to control rats. Rats infused with RFRP-3 exhibited significantly smaller testes compared to control rats. RFRP-3 rats also had a significant decrease in plasma LH levels. RFRP-3 infusion elicited a significant increase in growth hormone-releasing hormone mRNA and plasma growth hormone levels compared to control rats. Neither peptide had an effect on KiSS-1 mRNA expression. CONCLUSION: These data suggest that endogenous rat RFRP-3 does not affect the timing of puberty in male rats but may be associated with peripubertal rise in growth hormone secretion.

Effects of diabetes and insulin on the expression of galanin-like peptide in the hypothalamus of the rat.

Galanin-like peptide (GALP) is produced in a small population of neurons in the arcuate nucleus of the hypothalamus, and leptin stimulates the hypothalamic expression of GALP mRNA. Because insulin and leptin share common signaling pathways in the brain, we reasoned that GALP neurons might also be responsive to changes in circulating concentrations of insulin. To test this hypothesis, we first studied the effect of insulin deficiency on the expression of GALP by comparing levels of GALP mRNA between normal and diabetic animals. Streptozotocin-induced diabetes was associated with a significant reduction in the expression of GALP mRNA, which was reversed by treatment with either insulin or leptin. Second, we examined the effect of insulin administered directly into the brain on the expression of GALP mRNA in fasted rats. Hypothalamic levels of GALP mRNA were lower in animals after a 48-h fast, and central treatment with insulin reversed this effect. These results suggest that GALP neurons are direct targets for regulation by insulin and implicate these cells for a role in the metabolic and behavioral sequelae of type 1 diabetes.

Differential patterns of Fos induction in the hypothalamus of the rat following central injections of galanin-like peptide and galanin.

Galanin and its newly discovered relative galanin-like peptide (GALP) are neuropeptides that are implicated in the neuroendocrine regulation of body weight and reproduction. GALP has been shown to bind in vitro to galanin receptor subtypes 1 and 2, but whether it has its own specific receptor(s) is unknown. We reasoned that if GALP acts through a receptor that is distinct from galanin receptors, then GALP should activate central pathways that are different from those activated by galanin. The purpose of this study was to determine whether galanin and GALP produce different patterns of neuronal activation within the hypothalamus. Quantitative analysis of Fos immunoreactivity showed that galanin induced a significantly greater number of Fos-positive nuclei in the paraventricular nucleus compared with GALP (P < 0.001); however, compared with galanin, GALP induced significantly more Fos-positive cells in the horizontal limb of the diagonal band of Broca, caudal preoptic area, arcuate nucleus, and median eminence (P < 0.05). These observations suggest that GALP and galanin act through different receptor-mediated pathways to exert their effects on the regulation of body weight and reproduction and identify target cells for GALP's specific actions in the hypothalamus, including the preoptic area, paraventricular and arcuate nuclei, and the median eminence.