Galanin-like peptide as a link in the integration of metabolism and reproduction

Abstract

The arcuate nucleus is a hypothalamic center that couples energetics and reproduction. Peptide-releasing neurons in the arcuate nucleus receive and process humoral signals from the periphery and relay this information to other nuclei in the hypothalamus and preoptic area. Galanin-like peptide (GALP) is expressed in the arcuate nucleus, and GALP-containing neurons are targets for the action of leptin. GALP-containing neurons are closely apposed to gonadotropin-releasing hormone (GnRH) neurons in the preoptic area, and CNS injections of GALP stimulate GnRH-mediated secretion of luteinizing hormone. These observations indicate that GALP is a molecular signal that couples circulating indices of metabolism to the neuroendocrine reproductive system and, thus, regulates reproductive activity as a function of the energy state. In this article, we describe the involvement of GALP in metabolism and reproduction, and in the coupling between these two processes.The brain has a remarkable ability to sense the status of metabolic fuel reserves and defend their adequacy by adjusting appetite and metabolism to maintain an appropriate body weight. Moreover, the brain governs the activity of the reproductive system as a function of these metabolic reserves and enables activation of the hypothalamic -pituitary -gonadal axis only when fuel stores are deemed adequate to support the energetic requirements of reproduction. The arcuate nucleus (Arc) in the hypothalamus is a node for this physiological integration. Recently, a newly identified peptide in the Arc has been shown to modulate both feeding behavior and reproduction, which unveils a new link in the integration of metabolism and reproduction. In this review, we discuss the emerging role of this peptide, known as galanin-like peptide (GALP), in the physiological integration of metabolism and reproduction. The Arc integrates metabolism and reproductionThe Arc comprises the neuronal circuitry required for the neuroendocrine integration of metabolism and reproduction [1]. Two populations of neurons in the Arc play key roles in the regulation of these physiological processes. One population produces neuropeptide Y (NPY) and agouti-related peptide (AgRP), whereas the other produces a-melanocyte-stimulating hormone (a-MSH) and b-endorphin from a common precursor, proopiomelanocortin (POMC), and cocaine-and amphetamine-regulated transcript (CART). These two cell groups (NPY/AgRP and POMC/CART) are regulated differentially by metabolic hormones such as leptin and insulin, and act in opposition to control appetite, body weight and metabolic rate [1][2][3][4]. NPY/AgRP and POMC/CART neurons send axonal projections to the paraventricular nucleus (PVN), lateral hypothalamus, and areas in the midbrain and hindbrain to regulate the circuitry that controls complex behaviors, such as feeding, and adjust the metabolic rate to maintain body weight homeostasis [3,[5][6][7]. Disruption of these networks leads to the dysregulation of body weight and disturbances in metabolism [8]. The Arc is also a...

Expression of Hypothalamic KiSS-1 System and Rescue of Defective Gonadotropic Responses by Kisspeptin in Streptozotocin-Induced Diabetic Male Rats

“…However, those hormonal studies were carried out before cloning and/or characterization of key molecular signals in the integrated control of metabolism and reproductive function, such as leptin, GALP (galanin-like peptide), and, more recently, kisspeptin (2,35,39). Such recent developments force us to accommodate these new factors into the previously known hypoganodotropic phenotype of diabetes.…”

Caloric restriction: Impact upon pituitary function and reproduction

“…GALPpositive neurons appear to be directly stimulated by leptin as they possess the ObRb leptin receptor. It has been demonstrated that central administration of GALP stimulates GnRH release and subsequently LH secretion in numerous mammalian models (Gottsch et al, 2004b;Kauffman et al, 2005b). GALP expression, as one would expect by its leptin/insulin control, is profoundly reduced by implementation of CR regimes.…”

Galanin-like peptide: a key player in the homeostatic regulation of feeding and energy metabolism?

“…GALP reduces food intake and body weight to the same degree in GALR1-and GALR2-deficient mice when compared with wild-type mice, 30 and GALR2-deficient mice do not show abnormal feeding behavior. 15 Furthermore, the GALR2/3 agonist (AR-M1896) has no effect on feeding or body weight in either the rat or the mouse. 19 Therefore, more studies are required to determine the receptor mediating the anorectic actions of GALP but, as this peptide can act differently in rodents when compared with galanin, a new/unidentified GALP-specific receptor is likely to be involved.…”

“…12 To date, GALP has been shown to act as an agonist at all three galanin receptor subtypes in vitro, although it shows preference for GALR2 and GALR3, as compared with GALR1. 7,13 There is a considerable body of evidence linking GALP to the regulation of food intake, energy metabolism and reproduction, [13][14][15][16][17][18][19] as well as fluid intake. 20,21 Furthermore, recent reports have suggested that GALP has a role in conditions such as epilepsy, Alzheimer's disease 22 and diabetes, [22][23][24] in addition to serving a vasoactive function.…”