Elevated KiSS‐1 Expression in the Arcuate Nucleus Prior to the Cyclic Preovulatory Gonadotrophin‐Releasing Hormone/Lutenising Hormone Surge in the Ewe Suggests a Stimulatory Role for Kisspeptin in Oestrogen‐Positive Feedback

Estrada, Karla; Clay, Colin M.; Pompolo, Sueli; Smith, Jeremy Troy; Clarke, I. J.

doi:10.1111/j.1365-2826.2006.01485.x

Cited by 180 publications

(139 citation statements)

References 30 publications

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“…In rodents, kisspeptin-producing cells are found in the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (ARC) (Smith 2013). In sheep, kisspeptin neurons are located in the dorsolateral region of the preoptic area (POA) (perhaps a homologous population to the rodent AVPV) and the ARC (Estrada et al 2006, and estrogen regulation of kisspeptin has been extensively studied in these regions in both rodents and sheep (Smith 2013). Both neuronal populations are important in the generation of estrogenpositive feedback and sex steroid-negative feedback signals to GNRH neurons.…”

Section: Kisspeptin Governs Puberty Onset and Reproductionmentioning

confidence: 99%

Kisspeptin and energy balance in reproduction

Bond¹,

Smith²

2014

Reproduction

104

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Kisspeptin is vital for the neuroendocrine regulation of GNRH secretion. Kisspeptin neurons are now recognized as a central pathway responsible for conveying key homeostatic information to GNRH neurons. This pathway is likely to mediate the well-established link between energy balance and reproductive function. Thus, in states of severely altered energy balance (either negative or positive), fertility is compromised, as is Kiss1 expression in the arcuate nucleus. A number of metabolic modulators have been proposed as regulators of kisspeptin neurons including leptin, ghrelin, pro-opiomelanocortin (POMC), and neuropeptide Y (NPY). Whether these regulate kisspeptin neurons directly or indirectly will be discussed. Moreover, whether the stimulatory role of leptin on reproduction is mediated by kisspeptin directly will be questioned. Furthermore, in addition to being expressed in GNRH neurons, the kisspeptin receptor (Kiss1r) is also expressed in other areas of the brain, as well as in the periphery, suggesting alternative roles for kisspeptin signaling outside of reproduction. Interestingly, kisspeptin neurons are anatomically linked to, and can directly excite, anorexigenic POMC neurons and indirectly inhibit orexigenic NPY neurons. Thus, kisspeptin may have a direct role in regulating energy balance. Although data from Kiss1r knockout and WT mice found no differences in body weight, recent data indicate that kisspeptin may still play a role in food intake and glucose homeostasis. Thus, in addition to regulating reproduction, and mediating the effect of energy balance on reproductive function, kisspeptin signaling may also be a direct regulator of metabolism.

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Section: Kisspeptin Governs Puberty Onset and Reproductionmentioning

confidence: 99%

Kisspeptin and energy balance in reproduction

Bond¹,

Smith²

2014

Reproduction

104

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“…Interestingly, in the sheep, kisspeptin neurons mediating positive and negative feedback effects of sex steroids seem to be intermingled within the ARC; neurons responding positively to estrogen being mostly located at its caudal portion [23]. In primates, including humans, only inhibitory responses to sex steroids have been documented in ARC/infundibular neurons, as major mechanism for their negative feedback on gonadotropin secretion [24][25][26] (see Section 4).…”

Section: Control Of Gnrh Neurons By Kisspeptin Pathwaysmentioning

confidence: 99%

Kisspeptin signaling in the brain: Recent developments and future challenges

Tena‐Sempere

2010

Molecular and Cellular Endocrinology

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Kisspeptins, a family of peptides encoded by the KISS1 gene which binds GPR54 (or KISS1 receptor), have recently emerged as essential neuropeptide regulators of key aspects of reproductive maturation and function, including puberty onset, neuroendocrine control of ovulation and metabolic regulation of fertility. Yet, while the neuroanatomy of kisspeptin system has begun to be deciphered, and the involvement of kisspeptins in the above phenomena has been experimentally documented in recent years, precise information on the signaling events underlying these functions has remained scarce. Similarly, the nature and mechanisms of action of most of the regulatory signals of KISS1 expression in the brain are largely unknown. In this review, we will comprehensively summarize some of the recent developments in these areas of kisspeptin physiology, with the ultimate aim to delineate unresolved questions and future pathways for the progression of this active field of Neuroendocrinology.

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“…This anatomically-linked functional dimorphism of KP neurons is not evident in sheep and monkeys as both types of neurons appear to be localized in the ARC 91,97,98 .…”

Section: Introductionmentioning

confidence: 87%

“…Importantly, KP neurons express steroid hormone receptors [91][92][93][94] , and gonadectomy in rodents increases detectable KP cell numbers and mRNA expression levels in the arcuate nucleus (ARC), while steroid replacement reverses this. While KP neurons in the ARC mediate this steroid negative feedback control on GnRH neurons, another population in rodents in the anteriorventral paraventricular nucleus (AVPV)…”

Section: Introductionmentioning

confidence: 99%

Current and future applications of GnRH, kisspeptin and neurokinin B analogues

Millar

Newton

2013

Nat Rev Endocrinol

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Reproductive hormones impact on all stages of life from gamete production, fertilisation, fetal development and parturition, neonatal development and puberty through to adulthood and senescence.The reproductive hormone cascade has therefore been the target for the development of numerous drugs which modulate its activity at many levels. As the central regulator of the cascade, gonadotropinreleasing hormone (GnRH) agonists and antagonists have found extensive applications in treating a wide range of hormone-dependent deseases such as precocious puberty, prostate cancer, benign prostatic hyperplasia, endometriosis and uterine fibroids, as well as being an essential component of in vitro fertilisation (IVF) protocols. Recently-discovered neuroendocrine peptides, kisspeptin (KP) and neurokinin B (NKB), have also been identified as therapeutic targets and novel agonists and antagonists are being developed as modulators of the cascade upstream of GnRH. Here we review the development and applications of analogues of the major neuroendocrine peptide regulators of the reproductive hormone cascade, GnRH, KP and NKB.

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Elevated KiSS‐1 Expression in the Arcuate Nucleus Prior to the Cyclic Preovulatory Gonadotrophin‐Releasing Hormone/Lutenising Hormone Surge in the Ewe Suggests a Stimulatory Role for Kisspeptin in Oestrogen‐Positive Feedback

Cited by 180 publications

References 30 publications

Kisspeptin and energy balance in reproduction

Kisspeptin and energy balance in reproduction

Kisspeptin signaling in the brain: Recent developments and future challenges

Current and future applications of GnRH, kisspeptin and neurokinin B analogues

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