Rapid modulation of hypothalamic Kiss1 levels by the suckling stimulus in the lactating rat

Higo, Shimpei; Aikawa, Satoko; Iijima, Norio; Ozawa, Hitoshi

doi:10.1530/joe-15-0143

Cited by 20 publications

(18 citation statements)

References 44 publications

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“…In each ISH experiment, we used DIG‐ or fluorescein‐labelled sense probes for negative controls and confirmed the absence of nonspecific signals in the ARN. Primary antibodies for POMC, TH and kisspeptin used in the present study have been well characterised elsewhere . All of the immunofluorescent images from these antibodies were in good agreement with previous studies and no nonspecific signals were observed in primary antibody‐omitted controls.…”

Section: Methodssupporting

confidence: 88%

“…Previous studies have shown that kisspeptin expression dynamically changes in various reproductive conditions (e.g. across the oestrous cycle, lactation and pregnancy) . Considering that the expression of POMC and NPY also changes in response to various nutritional conditions , the co‐expression rate of Kiss1r in the ARN neuronal populations could vary depending on steroid milieus, reproductive conditions and nutritional conditions.…”

Section: Discussionmentioning

confidence: 99%

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Characterisation of Kiss1r (Gpr54)‐Expressing Neurones in the Arcuate Nucleus of the Female Rat Hypothalamus

Higo

Iijima

Ozawa

2017

J Neuroendocrinology

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Kisspeptin is essential in reproduction and acts by stimulating neurones expressing gonadotrophin-releasing hormone (GnRH). Recent studies suggest that kisspeptin has multiple roles in the modulation of neuronal circuits in systems outside the hypothalamic-pituitary-gonadal axis. Our recent research using in situ hybridisation (ISH) clarified the histological distribution of Kiss1r (Gpr54)-expressing neurones in the rat brain that were presumed to be putative targets of kisspeptin. The arcuate nucleus (ARN) of the hypothalamus is one of the brain regions in which Kiss1r expression in non-GnRH neurones is prominent. However, the characteristics of Kiss1r-expressing neurones in the ARN remain unclear. The present study aimed to determine the neurochemical characteristics of Kiss1r-expressing neurones in the ARN using ISH and immunofluorescence. We revealed that the majority (approximately 63%) of Kiss1r-expressing neurones in the ARN were pro-opiomelanocortin (POMC) neurones, which have an anorexic effect in mammals. Additionally, a few Kiss1r-expressing neurones in the dorsal ARN are tuberoinfundibular dopamine (TIDA) neurones, which control milk production by inhibiting prolactin secretion from the anterior pituitary. TIDA neurones showed a relatively weak Kiss1r ISH signal compared to POMC neurones, as well as low co-expression of Kiss1r (approximately 15%). We also examined the expression of Kiss1r in neuropeptide Y and kisspeptin neurones, which are reported to arise from POMC-expressing progenitor cells during development. However, the vast majority of neuropeptide Y and kisspeptin neurones in the ARN did not express Kiss1r. These results suggest that kisspeptin may directly regulate energy homeostasis and milk production by modulating the activity of POMC and TIDA neurones, respectively. Our results provide an insight into the wide variety of roles that kisspeptin plays in homeostatic and neuroendocrine functions.

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Section: Methodssupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Characterisation of Kiss1r (Gpr54)‐Expressing Neurones in the Arcuate Nucleus of the Female Rat Hypothalamus

Higo

Iijima

Ozawa

2017

J Neuroendocrinology

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“…In OVX rats, the administration of PRL decreases the ARC- and AVPV-kisspeptin expression, and level of plasma LH (Araujo-Lopes et al, 2014 ). Acute administration of PRL for 1 h can also reduce the level of AVPV- kiss1 mRNA (Higo et al, 2015 ). In TCS mice, the reduced ARC- or AVPV-kisspeptin expression was recovered by L-T4 or quinpirole that corrected the increase of PRL.…”

Section: Discussionmentioning

confidence: 99%

Impact of Triclosan on Female Reproduction through Reducing Thyroid Hormones to Suppress Hypothalamic Kisspeptin Neurons in Mice

Cao

Xiong

et al. 2018

Front. Mol. Neurosci.

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Triclosan (TCS), a broad-spectrum antimicrobial agent, is widely used in clinical settings and various personal care products. The aim of this study was to evaluate the influence of TCS on reproductive endocrine and function. Here, we show that the exposure of adult female mice to 10 or 100 mg/kg/day TCS caused prolongation of diestrus, and decreases in antral follicles and corpora lutea within 2 weeks. TCS mice showed decreases in the levels of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and progesterone, and gonadotrophin-releasing hormone (GnRH) mRNA with the lack of LH surge and elevation of prolactin (PRL). TCS mice had lower kisspeptin immunoreactivity and kiss1 mRNA in anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC). Moreover, the estrogen (E2)-enhanced AVPV-kisspeptin expression was reduced in TCS mice. In addition, the serum thyroid hormones (triiodothyronine (T3) and thyroxine (T4)) in TCS mice were reduced with increases in levels of thyroid stimulating hormone (TSH) and thyroid releasing hormone (TRH). In TCS mice, the treatment with Levothyroxine (L-T4) corrected the increases in PRL, TSH and TRH; the administration of L-T4 or type-2 dopamine receptors agonist quinpirole inhibiting PRL release could rescue the decline of kisspeptin expression in AVPV and ARC; the treatment with L-T4, quinpirole or the GPR45 agonist kisspeptin-10 recovered the levels of serum LH and FSH and progesterone, and GnRH mRNA. Furthermore, TCS mice treated with L-T4 or quinpirole resumed regular estrous cycling, follicular development and ovulation. Together, these results indicate that exposing adult female mice to TCS (≥10 mg/kg) reduces thyroid hormones causing hyperprolactinemia that then suppresses hypothalamic kisspeptin expression, leading to deficits in reproductive endocrine and function.

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“…48 The RP3V kisspeptin population is apparently harder to study in rats 59,64 providing conflicting findings, such as reports of Kiss1 mRNA remaining unchanged during lactation, 59 kisspeptin protein increasing while Kiss1 mRNA labeling decreased during lactation, 60 or even suckling-induced decrease of Kiss1 mRNA. 65 More importantly, we have also shown that the reduction in kisspeptin expression results in complete loss of capacity for these neurons to activate GnRH neurons, even if they are stimulated exogenously. 66 Given the similarity between the effect of suckling and the effect of prolactin, and the knowledge that suckling stimulates prolactin secretion, it seems likely that elevated prolactin during pregnancy and lactation contributes to the infertility of lactation, but this remains to be proven, and the relative roles of prolactin and/or suckling may change in different species.…”

Section: Role Of Prolactin In Lactational Infertilitymentioning

confidence: 75%

Kisspeptin and Prolactin

Grattan

Szawka

2019

Semin Reprod Med

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The relationship between elevated prolactin and infertility has been known for a long time, but the specific mechanism by which prolactin inhibited reproduction had been uncertain. The discovery of kisspeptin has provided novel insights into how prolactin might cause infertility, with extensive evidence that elevated prolactin inhibits secretion of kisspeptin, resulting in hypogonadotropic hypogonadism, and infertility. More recent data suggest that a converse relationship might also exist, with evidence that kisspeptin influences prolactin secretion. This brief review will examine the relationship between kisspeptin and prolactin from each of these two perspectives: the well-characterized inhibitory effect of prolactin on kisspeptin neurons and the more recent concept that kisspeptin neurons are involved in the control of prolactin secretion.

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Rapid modulation of hypothalamic Kiss1 levels by the suckling stimulus in the lactating rat

Cited by 20 publications

References 44 publications

Characterisation of Kiss1r (Gpr54)‐Expressing Neurones in the Arcuate Nucleus of the Female Rat Hypothalamus

Characterisation of Kiss1r (Gpr54)‐Expressing Neurones in the Arcuate Nucleus of the Female Rat Hypothalamus

Impact of Triclosan on Female Reproduction through Reducing Thyroid Hormones to Suppress Hypothalamic Kisspeptin Neurons in Mice

Kisspeptin and Prolactin

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