Abstract
Kisspeptin–GPR54 signaling in the hypothalamus is required for reproduction and fertility in mammals. Kiss1 neurons are key regulators of gonadotropin-releasing hormone (GnRH) release and modulation of the hypothalamic–pituitary–gonadal (HPG) axis. Arcuate Kiss1 neurons project to GnRH nerve terminals in the median eminence, orchestrating the pulsatile secretion of luteinizing hormone (LH) through the intricate interaction between GnRH pulse frequency and the pituitary gonadotrophs. Arcuate Kiss1 neurons, also known as KNDy neurons in rodents and ruminants because of their co-expression of neurokinin B and dynorphin represent an ideal hub to receive afferent inputs from other brain regions in response to physiological and environmental changes, which can regulate the HPG axis. This review will focus on studies performed primarily in rodent and ruminant species to explore potential afferent inputs to Kiss1 neurons with emphasis on the arcuate region but also considering the rostral periventricular region of the third ventricle (RP3V). Specifically, we will discuss how these inputs can be modulated by hormonal, metabolic, and environmental factors to control gonadotropin secretion and fertility. We also summarize the methods and techniques that can be used to study functional inputs into Kiss1 neurons.
Highlights
Kisspeptin, encoded by the Kiss1 gene, was initially proposed as a suppressor of metastasis, but its precise role in this process remains elusive [1, 2]
To eliminate the possibility of developmental adaptations and system redundancies, the leptin receptor (LepR) was selectively re-expressed in Kiss1 neurons of Lepr-null mice. These mice showed no pubertal development and no improvement of the metabolic phenotype: they remained obese, diabetic, and infertile [142]. These findings clearly demonstrate that Kiss1 neurons are not the direct target of leptin during puberty onset
The HPG axis must be able to respond to changes in endocrine, metabolic, or environmental cues to regulate gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) release
Summary
The Role of Kiss Neurons As Integrators of Endocrine, Metabolic, and Environmental Factors in the Hypothalamic–. Kiss neurons are key regulators of gonadotropin-releasing hormone (GnRH) release and modulation of the hypothalamic–pituitary–gonadal (HPG) axis. Arcuate Kiss neurons, known as KNDy neurons in rodents and ruminants because of their co-expression of neurokinin B and dynorphin represent an ideal hub to receive afferent inputs from other brain regions in response to physiological and environmental changes, which can regulate the HPG axis. This review will focus on studies performed primarily in rodent and ruminant species to explore potential afferent inputs to Kiss neurons with emphasis on the arcuate region and considering the rostral periventricular region of the third ventricle (RP3V). We will discuss how these inputs can be modulated by hormonal, metabolic, and environmental factors to control gonadotropin secretion and fertility.
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