Diurnal regulation of hypothalamic kisspeptin is disrupted during mouse pregnancy

Yap, Cassandra; Wharfe, Michaela D; Mark, Peter J.; Waddell, Brendan J.; Smith, Jeremy Troy

doi:10.1530/joe-16-0086

Cited by 6 publications

(4 citation statements)

References 45 publications

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“…In particular, the mechanisms underlying the altered energy balance in the absence of kisspeptin signalling remains to be elucidated. There are clear links between circadian rhythms and kisspeptin signalling (Yap et al 2016), and these may prove important in impairments in energy expenditure, which are more pronounced during the dark phase in Kiss1rKO mice (Tolson et al 2014). Importantly, to our knowledge, there are no current reports of human obesity associated with KISS1 or KISS1R mutations.…”

Section: Discussionmentioning

confidence: 94%

The role of kisspeptin neurons in reproduction and metabolism

Harter

Kavanagh

Smith

2018

Journal of Endocrinology

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122

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Kisspeptin is a neuropeptide with a critical role in the function of the hypothalamic-pituitary-gonadal (HPG) axis. Kisspeptin is produced by two major populations of neurons located in the hypothalamus, the rostral periventricular region of the third ventricle (RP3V) and arcuate nucleus (ARC). These neurons project to and activate gonadotrophin-releasing hormone (GnRH) neurons (acting via the kisspeptin receptor, Kiss1r) in the hypothalamus and stimulate the secretion of GnRH. Gonadal sex steroids stimulate kisspeptin neurons in the RP3V, but inhibit kisspeptin neurons in the ARC, which is the underlying mechanism for positive- and negative feedback respectively, and it is now commonly accepted that the ARC kisspeptin neurons act as the GnRH pulse generator. Due to kisspeptin's profound effect on the HPG axis, a focus of recent research has been on afferent inputs to kisspeptin neurons and one specific area of interest has been energy balance, which is thought to facilitate effects such as suppressing fertility in those with under- or severe over-nutrition. Alternatively, evidence is building for a direct role for kisspeptin in regulating energy balance and metabolism. Kiss1r-knockout (KO) mice exhibit increased adiposity and reduced energy expenditure. Although the mechanisms underlying these observations are currently unknown, Kiss1r is expressed in adipose tissue and potentially brown adipose tissue (BAT) and Kiss1rKO mice exhibit reduced energy expenditure. Recent studies are now looking at the effects of kisspeptin signalling on behaviour, with clinical evidence emerging of kisspeptin affecting sexual behaviour, further investigation of potential neuronal pathways are warranted.

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Section: Discussionmentioning

confidence: 94%

The role of kisspeptin neurons in reproduction and metabolism

Harter

Kavanagh

Smith

2018

Journal of Endocrinology

Self Cite

122

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“…These may be caused by inappropriate feedback mechanisms and result in the diminished GnRH/LH surge observed. Figure adapted from Yap et al [51]. …”

Section: Discussionmentioning

confidence: 99%

The Role of Central Androgen Receptor Actions in Regulating the Hypothalamic-Pituitary-Ovarian Axis

et al. 2018

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The androgen receptor (AR) is expressed throughout the hypothalamic-pituitary-gonadal (HPG) axis, and findings from female global AR knockout mice confirm that AR-mediated androgen actions play important roles in regulating female reproductive function. We generated neuron-specific AR knockout mice (NeurARKO) to investigate the functional role of neuronal AR-mediated androgen action in regulating the female HPG axis and fertility. Relative to control females, NeurARKO females exhibited elevated luteinizing hormone (LH) levels at diestrus (p < 0.05) and a compromised serum LH response to ovariectomy and E2 priming (p < 0.01). Furthermore, NeurARKO females displayed reduced Kiss1 mRNA expression in the anteroventral periventricular nucleus at diestrus (p < 0.05) and proestrus (p < 0.05), but elevated Kiss1 (p < 0.05) and neurokinin B (Tac2, p < 0.05) mRNA expression in the arcuate nucleus at proestrus compared to WT controls. Ovarian follicle dynamics were also altered in NeurARKO ovaries at 3 months of age, with a significant reduction in large antral follicle numbers at the proestrus stage compared to control WT ovaries (p < 0.05). Increased follicular atresia was evident in NeurARKO ovaries with a 4-fold increase in unhealthy large preantral follicles (p < 0.01). Despite the findings of aberrant neuroendocrine and ovarian characteristics in the NeurARKO females, estrous cyclicity and overall fertility were comparable between NeurARKO and WT females. In conclusion, our findings revealed that selective loss of neuronal AR actions impacts the kisspeptin/GnRH/LH cascade leading to compromised ovarian follicle dynamics.

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“…Changes in the pattern of gonadotropin secretion provide powerful information about physiological control mechanisms, such as the underlying characteristics of pulsatile GnRH secretion (11). Furthermore, GnRH neurons reside mainly in POA and ARC, where neurons are sensitive to kisspeptin, steroids, and circadian regulation of AVP (12)(13)(14). Over the last decade, a significant body of evidence has accumulated on the interconnections between circadian clocks and aging (15).…”

Section: Introductionmentioning

confidence: 99%

Vasopressinergic Activity of the Suprachiasmatic Nucleus and mRNA Expression of Clock Genes in the Hypothalamus-Pituitary-Gonadal Axis in Female Aging

et al. 2021

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The important involvement of the suprachiasmatic nucleus (SCN) and the activity of vasopressinergic neurons in maintaining the rhythmicity of the female reproductive system depends on the mRNA transcription-translation feedback loops. Therefore, circadian clock function, like most physiological processes, is involved in the events that determine reproductive aging. This study describes the change of mRNA expression of clock genes, Per2, Bmal1, and Rev-erbα, in the hypothalamus-pituitary-gonadal axis (HPG) of female rats with regular cycle (RC) and irregular cycle (IC), and the vasopressinergic neurons activity in the SCN and kisspeptin neurons in the arcuate nucleus (ARC) of these animals. Results for gonadotropins and the cFos/AVP-ir neurons in the SCN of IC were higher, but kisspeptin-ir was minor. Change in the temporal synchrony of the clock system in the HPG axis, during the period prior to the cessation of ovulatory cycles, was identified. The analysis of mRNA for Per2, Bmal1, and Rev-erbα in the reproductive axis of adult female rodents shows that the regularity of the estrous cycle is guaranteed by alternation in the amount of expression of Bmal1 and Per2, and Rev-erbα and Bmal1 between light and dark phases, which ceases to occur and contributes to determining reproductive senescence. These results showed that the desynchronization between the central and peripheral circadian clocks contributes to the irregularity of reproductive events. We suggest that the feedback loops of clock genes on the HPG axis modulate the spontaneous transition from regular to irregular cycle and to acyclicity in female rodents.

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Diurnal regulation of hypothalamic kisspeptin is disrupted during mouse pregnancy

Cited by 6 publications

References 45 publications

The role of kisspeptin neurons in reproduction and metabolism

The role of kisspeptin neurons in reproduction and metabolism

The Role of Central Androgen Receptor Actions in Regulating the Hypothalamic-Pituitary-Ovarian Axis

Vasopressinergic Activity of the Suprachiasmatic Nucleus and mRNA Expression of Clock Genes in the Hypothalamus-Pituitary-Gonadal Axis in Female Aging

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