Endocrine Abstracts

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...

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...

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...

RF-amide-related peptide-3 (RFRP-3), the mammalian orthologue of the avian gonadotropin-inhibiting hormone (GnIH), has been proposed as major inhibitory signal for the reproductive axis, acting via the NPFF1 receptor (NPFF1R). In addition, RFRP-3 has been recently suggested to modulate feeding, with reported orexigenic actions; a function that might contribute to the integrative control of energy homeostasis and reproduction. However, characterisation of the metabolic effects ...

While female fertility is known to be sensitive to conditions of low body fuel reserves, the reproductive consequences of persistent energy excess remain ill defined. Yet, the pandemic proportions of obesity, and its potential impact on the gonadotropic axis, call for a better understanding of this phenomenon. Alike, the influence of ovarian hormones on the pathophysiology of obesity and its complications merits further investigation. In this work, we aimed to elucidate the me...

Childhood obesity has become a major health problem, which is coupled to different adverse outcomes and diseases. The escalating prevalence of child obesity parallels that of alterations in pubertal timing, also linked to higher disease burden later on life. Yet, the mechanisms underlying for this association remain unfolded. Ceramides, ubiquitous signaling molecules involved in numerous biological processes, have emerged as mediators of metabolic disorders and transmitters fo...

GnRH neurons are the final output of the brain controlling reproduction. These neurons receive information from multiple central and peripheral signals, ranging from gonadal steroids to metabolic cues and brain neuropeptides, to regulate their activity. AMP-activated protein kinase (AMPK) is an intracellular sensor, activated by energy deficiency, involved in the regulation of the cellular and whole-body energy homeostasis. Previous in vitro studies suggested the part...