Endocrine Abstracts

Neuromedin U (NMU) is a brain-gut peptide originally isolated from porcine spinal cord, and later found in other species. NMU acts through two receptors named NMU1R (abundant in peripheral tissues) and NMU2R (apparently restricted to specific brain regions). Besides its potential implication in the control of stress responses, NMU is abundantly expressed in the ventromedial hypothalamic area and has been involved, as satiety factor, in the regulation of food intake. Very recen...

The G protein-coupled receptor (GPCR) kinase 2, GRK2, is a ubiquitous serine/threonine protein kinase that is able to phosphorylate and desensitize the active form of several GPCR. Compelling, as yet limited, evidence from in vitro studies have suggested a potential role of GRK2 in mediating desensitization of Gpr54, the canonical receptor for kisspeptins that is abundantly expressed in GnRH neurons. Yet, although kisspeptins have been universally recognized as essent...

Obesity and its comorbidities are reaching epidemic proportions. Maternal obesity is known to predispose the offspring to metabolic disorders, independently of genetic inheritance. This intergenerational transmission has also been suggested for paternal obesity during the pre-conception stage, as it appears to have a negative impact on the metabolic and reproductive health of the offspring, likely via epigenetic changes in spermatozoa. However, whether paternal obesity sensiti...

KNDy neurons, which co-express kisspeptins, neurokinin B (NKB) and dynorphin (Dyn), play a key role in the tonic control of gonadotropin secretion by modulating the GnRH release. The assumed KNDy model proposes that NKB and Dyn (as stimulatory and inhibitory signals, respectively) auto-regulate the secretion of kisspeptins onto GnRH neurons. However, some aspects of this paradigm remain poorly defined. In this context, the aims of this work were to characterize i) the putative...

Recent studies in various species have pointed out that Neurokinin B (NKB), encoded by Tac2 in rodents, and its receptor, NK3R, are important regulators of reproduction. NKB is co-expressed in Kiss1 neurons of the arcuate nucleus (ARC) and stimulates, via auto-regulatory loops, kisspeptin output onto GnRH neurons, therefore stimulating gonadotropin secretion. However, important aspects of the roles of NKB as regulators of the gonadotropic axis remain unknown. We report here th...

Introduction: Kisspeptins, the products of the Kiss1 gene that act via the receptor, GPR54 (or Kiss1R), are pivotal elements in the neuroendocrine control of GnRH neurons and, thereby, gonadotropin secretion. Extensive efforts have been devoted recently to elucidate the pharmacological effects and major putative regulators of the kisspeptin system. Yet, our knowledge on the potential interactions of kisspeptins with other key neurotransmitters involved in the central re...

The hypothalamic peptide, nesfatin-1, derived from the precursor NEFA/nucleobindin2 (NUCB2), was recently identified as central anorexigenic molecule, acting in a leptin-independent manner. Yet, its potential involvement in the regulation of other biological functions gated by body energy status remains unexplored. We show herein that NUCB2/nesfatin-1 is involved in the control of female puberty. NUCB2/nesfatin mRNA and protein were detected at the hypothalamus of pubertal fem...

It is now widely accepted that the kisspeptins (kps) and their receptor kiss1r play an essential role in the neuroendocrine regulation of the reproductive axis by stimulating hypothalamic GnRH secretion. However, kiss1 and kiss1r expression in tissues distinct from, but related to, the hypothalamus, prompted us to propose that these molecules may exert regulatory functions in additional places of the neuroendocrine system, such as the pituitary and two of its phy...

The adipose tissue is an active endocrine organ involved in the control not only of metabolism and energy balance, but also of other relevant body functions, including reproduction. Adiponectin is an adipocyte hormone, with relevant roles in lipid metabolism and glucose homeostasis, recently involved in the control of different endocrine organs, such as the placenta, pituitary and, likely, the ovary. However, whether as described previously for other adipokines, such as leptin...

Reproduction is tightly coupled to body energy and metabolic status. GnRH neurons, the final output pathway for the brain control of reproduction, directly or indirectly receive and integrate multiple signals, including metabolic cues regulating reproductive function. Yet, the molecular underpinnings of such phenomenon remain largely unfolded. AMP-activated protein kinase (AMPK), a fundamental cellular sensor that becomes activated in conditions of energy deficit, has a key ro...