Hypothalamic neuroendocrine integration of reproduction and metabolism in mammals

Abstract

Reproduction in mammals is an extremely energy-intensive process and is therefore tightly controlled by the body's energy status. Changes in the nutritional status of the body cause fluctuations in the levels of peripheral metabolic hormone signals, such as leptin, insulin, and ghrelin, which provide feedback to the hypothalamus and integrate to coordinate metabolism and fertility. Therefore, to link energy and reproduction, energetic information must be centrally transmitted to Gonadotropin-releasing hormone (GnRN) neurons that act as reproductive gating. However, GnRH neurons themselves are rarely directly involved in energy information perception. Firstly, as key factors in the control of GnRH neurons, we describe the direct role of Kisspeptin and Arg-Phe amide-related peptide-3(RFRP-3) neurons in mediating metabolic signaling. Secondly, we focused on summarizing the roles of metabolic hormone-sensitive neurons in mediating peripheral energy hormone signaling. Some of these hormone-sensitive neurons can directly transmit energy information to GnRH neurons, such as Orexin neurons, etc., while others act indirectly through other neurons such as Kisspeptin and RFRP-3 neuron, such as (Pituitary adenylate cyclase-activating polypeptide)PACAP neurons, etc. In addition, as another important aspect of the integration of metabolism and reproduction, the impact of reproductive signaling itself on metabolic function were also considered, as exemplified by our examination of the role of Kisspeptin and RFRP-3 in feeding control. This review summarizes the latest research progress in related fields, in order to more fully understand the central neuropeptide network that integrates energy metabolism and reproduction.

A comprehensive chemotyping and gonadal regulation of seven kisspeptinergic neuronal populations in the mouse brain

“…It is known that the PMV neurons express the leptin receptor (Elmquist et al 1998). Moreover, a recent publication showed that PACAP-glutamatergic neurons that respond to leptin, located in the PMV can regulate the release of GnRH by innervating a subset of Kisspeptin neurons in the Arc and in the RP3V (Yang et al 2023).…”

Kisspeptin fiber and receptor distribution analysis suggests its potential role in central sensorial processing and behavioral state control

“…Besides the reproduction-linked behavioral functions of the Kp system extensively reported in the literature, another topic widely discussed is kisspeptin's role in energy balance control (Navarro 2020, Yang, Zhao et al 2023. A series of studies showed that female Kiss1r KO mice displayed decreased metabolism and obesity despite decreased feeding (Tolson, Garcia et al 2014, Tolson, Garcia et al 2016, Tolson, Marooki et al 2019) and that kisspeptin can modulate the activity of hypothalamic hunger/satiety circuits (Fu andvan den Pol 2010, Nestor, Qiu et al 2016).…”

Current Insights in Prolactin Signaling and Ovulatory Function

“…Clinical algorithms for kisspeptin treatment in ovulation disorders are constantly being developed due to the beneficial effect of this neuropeptide on follicle maturation, as assessed by maturity-related gene expression [327]. Therefore, the variability of the functional balance within the PRLkisspeptin interaction may determine the dominant influence of GnRH or PRL on a given stage of the sexual cycle, including ovulation [13,[328][329][330].…”