Kisspeptins: Bridging energy homeostasis and reproduction

Castellano, Juan Manuel Parreño; Bentsen, Agnete H.; Mikkelsen, Jens D.; Tena‐Sempere, Manuel

doi:10.1016/j.brainres.2010.08.057

Cited by 156 publications

(116 citation statements)

References 62 publications

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“…The participants were fasted during the IVGTTs, and fasting has been shown to reduce hypothalamic kisspeptin expression 45. However, as shown in Figure 1B, kisspeptin administration significantly raised plasma kisspeptin levels, and therefore would be sufficient to overcome the effect of suppression of endogenous kisspeptin by fasting.…”

Section: Discussionmentioning

confidence: 99%

The effects of kisspeptin on β‐cell function, serum metabolites and appetite in humans

Izzi‐Engbeaya

Comninos

Clarke

et al. 2018

Diabetes Obesity Metabolism

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AimsTo investigate the effect of kisspeptin on glucose‐stimulated insulin secretion and appetite in humans.Materials and methodsIn 15 healthy men (age: 25.2 ± 1.1 years; BMI: 22.3 ± 0.5 kg m−2), we compared the effects of 1 nmol kg−1 h−1 kisspeptin versus vehicle administration on glucose‐stimulated insulin secretion, metabolites, gut hormones, appetite and food intake. In addition, we assessed the effect of kisspeptin on glucose‐stimulated insulin secretion in vitro in human pancreatic islets and a human β‐cell line (EndoC‐βH1 cells).ResultsKisspeptin administration to healthy men enhanced insulin secretion following an intravenous glucose load, and modulated serum metabolites. In keeping with this, kisspeptin increased glucose‐stimulated insulin secretion from human islets and a human pancreatic cell line in vitro. In addition, kisspeptin administration did not alter gut hormones, appetite or food intake in healthy men.ConclusionsCollectively, these data demonstrate for the first time a beneficial role for kisspeptin in insulin secretion in humans in vivo. This has important implications for our understanding of the links between reproduction and metabolism in humans, as well as for the ongoing translational development of kisspeptin‐based therapies for reproductive and potentially metabolic conditions.

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Section: Discussionmentioning

confidence: 99%

The effects of kisspeptin on β‐cell function, serum metabolites and appetite in humans

Izzi‐Engbeaya

Comninos

Clarke

et al. 2018

Diabetes Obesity Metabolism

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“…On the former, accumulating evidence has demonstrated that Kiss1 neurons in the hypothalamus are sensitive to different forms of metabolic stress and thus may operate as conduits for the transmission of metabolic cues to the centers controlling puberty (18,46). As an example, situations of negative energy balance, such as acute fasting, have been shown to suppress Kiss1 mRNA expression and kisspeptin content in the hypothalamus of pubertal rats (55,56). Conversely, administration of kisspeptin is sufficient to partially reverse the state of hypogonadotropism and delayed puberty caused by chronic under-nutrition in prepubertal female rats (55).…”

Section: Kisspeptins: Major Gatekeepers Of Pubertymentioning

confidence: 99%

ENDOCRINOLOGY AND ADOLESCENCE: Deciphering puberty: novel partners, novel mechanisms

Tena‐Sempere

2012

European Journal of Endocrinology

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Puberty is a fascinating developmental phase that involves the attainment of reproductive capacity and the completion of sexual and somatic maturation. As a life-changing event, puberty onset is precisely controlled by interconnected regulatory pathways that are sensitive to numerous endogenous signals and environmental cues. The mechanisms of normal puberty and its potential deviations have been thoroughly studied in humans and model species. Yet, characterization of the neurobiological basis of puberty is still incomplete. Progress on this front is not only relevant from a physiological perspective but would also help to unravel the underlying causes for the observed changes in the timing of puberty in humans, with a trend for earlier puberty onset, especially in girls. In this review, we will provide a synoptic overview of some recent developments in the field that have deepened our understanding of the neuroendocrine and molecular basis for the control of puberty onset. These include not only the demonstration of the involvement of the hypothalamic Kiss1 system in the control of puberty and its modulation by metabolic cues but also the identification of the roles of other neuropeptide pathways and molecular mediators in the regulation of puberty. In addition, the potential contribution of novel regulatory mechanisms, such as epigenetics, in the central control of puberty will be briefly discussed. Characterization of these novel players and regulatory mechanisms will improve our understanding of the basis of normal puberty and its eventual alterations in various pathological conditions. European Journal of Endocrinology 167 733-747

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“…The endogenous G-protein-coupled receptor 54 (GPR54) ligand, kisspeptin, has been identified as the most potent secretagogue of GNRH (Irwig et al 2004) and is likewise implicated in the timing of puberty onset (Han et al 2005) and the mechanism whereby energy status is relayed to the reproductive axis (Tena-Sempere 2006, Castellano et al 2010, De Bond et al 2016. Although kisspeptin gene (Kiss1) expression is primarily regulated by gonadal steroid hormones (Smith 2009), it is also modulated by metabolic status such that its expression becomes reduced in response to metabolic stress, such as fasting (Castellano et al 2005) or prolonged high-fat diet feeding (Quennell et al 2011).…”

Section: Kisspeptin-expressing Neuronsmentioning

confidence: 99%

Neuroendocrine integration of nutritional signals on reproduction

Evans

Anderson

2017

Journal of Molecular Endocrinology

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Reproductive function in mammals is energetically costly and therefore tightly regulated by nutritional status. To enable this integration of metabolic and reproductive function, information regarding peripheral nutritional status must be relayed centrally to the gonadotropin-releasing hormone (GNRH) neurons that drive reproductive function. The metabolically relevant hormones leptin, insulin and ghrelin have been identified as key mediators of this 'metabolic control of fertility'. However, the neural circuitry through which they act to exert their control over GNRH drive remains incompletely understood. With the advent of Cre-LoxP technology, it has become possible to perform targeted gene-deletion and gene-rescue experiments and thus test the functional requirement and sufficiency, respectively, of discrete hormone-neuron signaling pathways in the metabolic control of reproductive function. This review discusses the findings from these investigations, and attempts to put them in context with what is known from clinical situations and wild-type animal models. What emerges from this discussion is clear evidence that the integration of nutritional signals on reproduction is complex and highly redundant, and therefore, surprisingly difficult to perturb. Consequently, the deletion of individual hormone-neuron signaling pathways often fails to cause reproductive phenotypes, despite strong evidence that the targeted pathway plays a role under normal physiological conditions. Although transgenic studies rarely reveal a critical role for discrete signaling pathways, they nevertheless prove to be a good strategy for identifying whether a targeted pathway is absolutely required, critically involved, sufficient or dispensable in the metabolic control of fertility.

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Kisspeptins: Bridging energy homeostasis and reproduction

Cited by 156 publications

References 62 publications

The effects of kisspeptin on β‐cell function, serum metabolites and appetite in humans

The effects of kisspeptin on β‐cell function, serum metabolites and appetite in humans

ENDOCRINOLOGY AND ADOLESCENCE: Deciphering puberty: novel partners, novel mechanisms

Neuroendocrine integration of nutritional signals on reproduction

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