Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Puberty, as the end-point of a complex series of maturational events affecting the components of the hypothalamic-pituitary-gonadal (HPG) axis, is gated by the state of body energy reserves and sensitive to different metabolic cues; conditions of severe metabolic stress and energy unbalance (from anorexia to morbid obesity) being commonly linked to perturbation of the onset of puberty. In the last two decades, the neuroendocrine mechanisms responsible for the tight coupling between energy homeostasis and puberty onset have begun to be deciphered. These seemingly involve a plethora of metabolic hormones and neuropeptides, which impinge and integrate (mostly) at the hypothalamic centers governing reproduction. Yet, characterization of the mechanisms of action of such regulators (and even their nature and physiological relevance) still remains incomplete. In this review, we will summarize some recent developments in our knowledge of the effects and mechanisms of action of two key metabolic hormones, leptin and ghrelin, in the control of puberty onset. In addition, the roles of the hypothalamic Kiss1 system in the metabolic gating of puberty will be reviewed, with special attention to its regulation by leptin and the recent identification of the putative roles of Crtc1 and mTOR signaling as molecular conduits for the metabolic control of Kiss1 expression. Elucidation of these novel players and regulatory mechanisms will help for a better understanding of the determinants of the timing of puberty, and its eventual alterations in adverse metabolic conditions.
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PMID:Metabolic control of puberty onset: new players, new mechanisms. 2002 41

Body energy reserves and metabolic state are relevant modifiers of puberty onset and fertility; forms of metabolic stress ranging from persistent energy insufficiency to morbid obesity are frequently linked to reproductive disorders. The mechanisms for such a close connection between energy balance and reproduction have been the subject of considerable attention; however, our understanding of the neurobiological basis for this phenomenon is still incomplete. In mid 1990s, the adipose-hormone, leptin, was proven as an essential signal for transmitting metabolic information onto the centers governing puberty and reproduction; yet, the ultimate mode of action of leptin on GnRH neurons has remained contentious for years. More recently, kisspeptins, a family of neuropeptides encoded by the Kiss1 gene, have emerged as conduits for the metabolic regulation of reproduction and putative effectors of leptin actions on GnRH neurons. This review recapitulates the experimental evidence obtained to date, mostly in laboratory rodents, supporting the function of kisspeptins in bridging energy balance and reproduction, with special emphasis on recent developments in this field, such as the recognition of mTOR (mammalian target of rapamycin) and Crtc1 (Creb1-regulated transcription coactivator-1) as putative mediators for leptin regulation of Kiss1 expression, as well as the identification of other potential metabolic modulators of kisspeptin signaling, such as ghrelin, neuropeptide Y (NPY) and melanin-concentrating hormone (MCH).
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PMID:Kisspeptins: bridging energy homeostasis and reproduction. 2080 54