Metabolic control of female puberty: potential therapeutic targets

ABSTRACT

Introduction: The onset of puberty in females is highly sensitive to the nutritional status and the amount of energy reserves of the organism. This metabolic information is sensed and transmitted to hypothalamic GnRH neurons, considered to be ultimately responsible for triggering puberty through the coordinated action of different peripheral hormones, central neurotransmitters, and molecular mediators.

Areas covered: This article will review and discuss (i) the relevant actions of the adipose hormone leptin, as a stimulatory/permissive signal, and the gut hormone ghrelin, as an inhibitory factor, in the metabolic control of female puberty; (ii) the crucial role of the hypothalamic kisspeptin neurons, recently emerged as essential gatekeepers of puberty, in transmitting this metabolic information to GnRH neurons; and (iii) the potential involvement of key cellular energy sensors, such as mTOR, as molecular mediators in this setting.

Expert opinion: The thorough characterization of the physiological roles of the above elements in the metabolic control of female puberty, along with the discovery of novel factors, pathways, and mechanisms involved, will promote our understanding of the complex networks connecting metabolism and puberty and, ultimately, will aid in the design of target-specific treatments for female pubertal disorders linked to conditions of metabolic stress.

KEYWORDS:

• Kisspeptin
• puberty
• leptin
• ghrelin
• mTOR
• energy balance
• obesity

Article highlights

• Female puberty is highly sensitive to metabolic conditions and the amount of energy reserves of the organism.

• The adipose hormone leptin, as a stimulatory/permissive signal, and the gut hormone ghrelin, as an inhibitory factor, operate as functional antagonists in the metabolic control of puberty.

• The hypothalamic Kisspeptin neurons are involved in transmitting metabolic information, mostly provided by leptin, to GnRH neurons.

• The cellular energy sensors, such as mTOR, participate as molecular mediators in the metabolic control of female puberty by affecting the hypothalamic expression of Kiss1 mRNA.

• The design of successful treatments for female pubertal disorders linked to metabolic stress will depend largely on the exhaustive characterization of the known targets and the identification of novel factors, pathways and mechanisms.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

The research leading to these results has received funding from the Junta de Andalucía (MTS: P08-CVI-03788 and P12-FQM-01943), Instituto de Salud Carlos III (ISCIII) (PIE14/00005), MINECO co-funded by the FEDER Program of EU (BFU2011-25021, BFU2014-57581 and SAF2014-56995-JIN) and EU research contract DEER FP7-ENV-2007-1. CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of ISCIII.