KNDy Hypothesis for Generation of GnRH Pulses: Evidence from Sheep and Goats

Goodman, Robert L.; Okhura, Satoshi; Okamura, Hiroaki; Coolen, Lique M.; Lehman, Michael N.

doi:10.1002/9781119233275.ch12

Cited by 19 publications

(21 citation statements)

References 78 publications

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“…Additionally, our previous studies in goats suggest that ARC kisspeptin neurons provably serve as a part of the GnRH pulse generating mechanism, because periodic bursts of multiple unit activity, corresponding to LH pulses, were successfully recorded from electrodes placed near the cluster of ARC kisspeptin neurons in goats [20, 55]. The current understanding of the molecular mechanism of GnRH pulse generation has been recently reviewed elsewhere [56, 57].…”

Section: Molecular Mechanism By Which Estrogen Regulates Kiss1 Expresmentioning

confidence: 99%

The roles of kisspeptin in the mechanism underlying reproductive functions in mammals

Uenoyama

Inoue

Maeda

et al. 2018

Journal of Reproduction and Development

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Kisspeptin, identified as a natural ligand of GPR54 in 2001, is now considered as a master regulator of puberty and subsequent reproductive functions in mammals. Our previous studies using Kiss1 knockout (KO) rats clearly demonstrated the indispensable role of kisspeptin in gonadotropin-releasing hormone (GnRH)/gonadotropin secretion. In addition, behavioral analyses of Kiss1 KO rats revealed an organizational effect of kisspeptin on neural circuits controlling sexual behaviors. Our studies using transgenic mice carrying a region-specific Kiss1 enhancer-driven reporter gene provided a clue as to the mechanism by which estrogen regulates Kiss1 expression in hypothalamic kisspeptin neurons. Analyses of Kiss1 expression and gonadotropin secretion during the pubertal transition shed light on the mechanism triggering GnRH/gonadotropin secretion at the onset of puberty in rats. Here, we summarize data obtained from the aforementioned studies and revisit the physiological roles of kisspeptin in the mechanism underlying reproductive functions in mammals.

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Section: Molecular Mechanism By Which Estrogen Regulates Kiss1 Expresmentioning

confidence: 99%

The roles of kisspeptin in the mechanism underlying reproductive functions in mammals

Uenoyama

Inoue

Maeda

et al. 2018

Journal of Reproduction and Development

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“…Circumstantial evidence suggests that the hypothalamic kisspeptin neurons, located in two nuclei, such as the anteroventral periventricular nucleus-periventricular nucleus (AVPV-PeN) continuum (also known as the rostral periventricular region of the third ventricle, or RP3V) and the hypothalamic arcuate nucleus (ARC), are functionally distinct: AVPV-PeN kisspeptin neurons are indicated to be responsible for GnRH/luteinizing hormone (LH) surge generation in rodents [ 10 , 11 , 12 , 13 , 14 , 15 ], whereas the ARC ones are suggested to be involved in GnRH/LH pulse generation in rodents and ruminants [ 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Indeed, AVPV-PeN Kiss1 ablation by neonatal sex steroid exposure resulted in a deficiency of the LH surge in female rats [ 14 , 15 ].…”

mentioning

confidence: 99%

Conditional kisspeptin neuron-specific Kiss1 knockout with newly generated Kiss1-floxed and Kiss1-Cre mice replicates a hypogonadal phenotype of global Kiss1 knockout mice

et al. 2020

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The present study aimed to evaluate whether novel conditional kisspeptin neuron-specific Kiss1 knockout (KO) mice utilizing the Cre-loxP system could recapitulate the infertility of global Kiss1 KO models, thereby providing further evidence for the fundamental role of hypothalamic kisspeptin neurons in regulating mammalian reproduction. We generated Kiss1-floxed mice and hypothalamic kisspeptin neuron-specific Cre-expressing transgenic mice and then crossed these two lines. The conditional Kiss1 KO mice showed pubertal failure along with a suppression of gonadotropin secretion and ovarian atrophy. These results indicate that newly-created hypothalamic Kiss1 KO mice obtained by the Cre-loxP system recapitulated the infertility of global Kiss1 KO models, suggesting that hypothalamic kisspeptin, but not peripheral kisspeptin, is critical for reproduction. Importantly, these Kiss1-floxed mice are now available and will be a valuable tool for detailed analyses of roles of each population of kisspeptin neurons in the brain and peripheral kisspeptin-producing cells by the spatiotemporal-specific manipulation of Cre expression.

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“…The recent acceptance that the MUA recorded in the vicinity of the arcuate nucleus is generated by KNDy neurons 40 , thereby confirming the view long held by some that MUA is indeed an electrophysiological property of the GnRH pulse generator, adds considerable importance to earlier goat studies that had monitored this activity while pharmacologically probing signaling by KNDy peptides within the arcuate network of KNDy neurons. Specifically, ICV injection of dynorphin to ovariectomized animals interrupted spontaneous volleys of MUA whereas administration of a KOR antagonist (nor-binaltorphimine, or nor-BNI) resulted in a marked acceleration in this electrophysiological parameter and an increase in the duration of the volley 81 , 82 VI . On the other hand, neurokinin B evoked an immediate MUA volley or train of such volleys.…”

Section: Mechanism Timing Pulsatile Arcuate Kisspeptin Release In Thementioning

confidence: 98%

The neurobiological mechanism underlying hypothalamic GnRH pulse generation: the role of kisspeptin neurons in the arcuate nucleus

Plant

2020

F1000Res

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This review recounts the origins and development of the concept of the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator. It starts in the late 1960s when striking rhythmic episodes of luteinizing hormone secretion, as reflected by circulating concentrations of this gonadotropin, were first observed in monkeys and ends in the present day. It is currently an exciting time witnessing the application, primarily to the mouse, of contemporary neurobiological approaches to delineate the mechanisms whereby Kiss1/NKB/Dyn (KNDy) neurons in the arcuate nucleus of the hypothalamus generate and time the pulsatile output of kisspeptin from their terminals in the median eminence that in turn dictates intermittent GnRH release and entry of this decapeptide into the primary plexus of the hypophysial portal circulation. The review concludes with an examination of questions that remain to be addressed.

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KNDy Hypothesis for Generation of GnRH Pulses: Evidence from Sheep and Goats

Cited by 19 publications

References 78 publications

The roles of kisspeptin in the mechanism underlying reproductive functions in mammals

The roles of kisspeptin in the mechanism underlying reproductive functions in mammals

Conditional kisspeptin neuron-specific <i>Kiss1</i> knockout with newly generated <i>Kiss1</i>-floxed and <i>Kiss1</i>-Cre mice replicates a hypogonadal phenotype of global <i>Kiss1</i> knockout mice

The neurobiological mechanism underlying hypothalamic GnRH pulse generation: the role of kisspeptin neurons in the arcuate nucleus

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