Action of neurotensin, corticotropin-releasing hormone, and RFamide-related peptide-3 in E2-induced negative feedback control: studies using a mouse arcuate nucleus hypothalamic cell model†

Tumurbaatar, Tuvshintugs; Kanasaki, Haruhiko; Oride, Aki; Hara, Toshiko; Okada, Hiroe; Tsutsui, Kazuyoshi; Kyo, Satoru

doi:10.1093/biolre/ioy145

Cited by 14 publications

(5 citation statements)

References 52 publications

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“…Other experimental paradigms indirectly suggest a possible influence of E2 on RFRP-3 neurons. For example, E2 treatment increases RFRP-3 synthesis in the hypothalamic mHypoA-55 rat cell line (111). In Syrian hamsters, food-restriction increases the percentage of RFRP-3 cells expressing c-Fos , with increased ovarian steroids at the time of estrus abolishing the impact of food restriction on RFRP-3 cellular activation (112).…”

Section: Rfrp-3 Contributes To the Daily Rhythm Of Reproduction In Fementioning

confidence: 99%

Functional Implications of RFRP-3 in the Central Control of Daily and Seasonal Rhythms in Reproduction

et al. 2019

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Adaptation of reproductive activity to environmental changes is essential for breeding success and offspring survival. In mammals, the reproductive system displays regular cycles of activation and inactivation which are synchronized with seasonal and/or daily rhythms in environmental factors, notably light intensity and duration. Thus, most species adapt their breeding activity along the year to ensure that birth and weaning of the offspring occur at a time when resources are optimal. Additionally, female reproductive activity is highest at the beginning of the active phase during the period of full oocyte maturation, in order to improve breeding success. In reproductive physiology, it is therefore fundamental to delineate how geophysical signals are integrated in the hypothalamo-pituitary-gonadal axis, notably by the neurons expressing gonadotropin releasing hormone (GnRH). Several neurochemicals have been reported to regulate GnRH neuronal activity, but recently two hypothalamic neuropeptides belonging to the superfamily of (Arg)(Phe)-amide peptides, RFRP-3 and kisspeptin, have emerged as critical for the integration of environmental cues within the reproductive axis. The goal of this review is to survey the current understanding of the role played by RFRP-3 in the temporal regulation of reproduction, and consider how its effect might combine with that of kisspeptin to improve the synchronization of reproduction to environmental challenges.

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Section: Rfrp-3 Contributes To the Daily Rhythm Of Reproduction In Fementioning

confidence: 99%

Functional Implications of RFRP-3 in the Central Control of Daily and Seasonal Rhythms in Reproduction

et al. 2019

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“…mHypoA-55 cells originated from mouse hypothalamic Kiss-1 neurons located in the ARC. These cells were defined as KNDy neurons because they express NKB (Tac3), DynA, and Kiss-1, and show a similar response to E2 stimulation on Kiss-1 gene expression [ 23 , 24 ]. Testosterone stimulation induced Kiss-1 gene and kisspeptin protein expression with a concomitant increase in Tac3 gene expression and NKB protein levels.…”

Section: Discussionmentioning

confidence: 99%

“…Kiss-1-expressing mHypoA-55 cells are a model of KNDy neurons that were isolated from the ARC of an adult female mouse. These cells co-express NKB, DynA, and Kiss-1, and Kiss-1 gene expression can be repressed in these cells by E2 under certain experimental conditions [ 23 , 24 ]. Using these cells, we investigated how androgens directly affect KNDy neurons in the hypothalamus.…”

Section: Introductionmentioning

confidence: 99%

Hyperandrogenism induces proportional changes in the expression of Kiss-1, Tac2, and DynA in hypothalamic KNDy neurons

Okada

Kanasaki

Tumurbaatar

et al. 2022

Reprod Biol Endocrinol

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Background Kisspeptin released from Kiss-1 neurons in the hypothalamus plays an essential role in the control of the hypothalamic–pituitary–gonadal axis by regulating the release of gonadotropin-releasing hormone (GnRH). In this study, we examined how androgen supplementation affects the characteristics of Kiss-1 neurons. Methods We used a Kiss-1-expressing mHypoA-55 cell model that originated from the arcuate nucleus (ARC) of the mouse hypothalamus. These cells are KNDy neurons that co-express neurokinin B (NKB) and dynorphin A (DynA). We stimulated these cells with androgens and examined them. We also examined the ARC region of the hypothalamus in ovary-intact female rats after supplementation with androgens. Results Stimulation of mHypoA-55 cells with 100 nM testosterone significantly increased Kiss-1 gene expression by 3.20 ± 0.44-fold; testosterone also increased kisspeptin protein expression. The expression of Tac3, the gene encoding NKB, was also increased by 2.69 ± 0.64-fold following stimulation of mHypoA-55 cells with 100 nM testosterone. DynA gene expression in these cells was unchanged by testosterone stimulation, but it was significantly reduced at the protein level. Dihydrotestosterone (DHT) had a similar effect to testosterone in mHypoA-55 cells; kisspeptin and NKB protein expression was significantly increased by DHT, whereas it significantly reduced DynA expression. In ovary-intact female rats, DTH administration significantly increased the gene expression of Kiss-1 and Tac3, but not DynA, in the arcuate nucleus. Exogenous NKB and DynA stimulation failed to modulate Kiss-1 gene expression in mHypoA-55 cells. Unlike androgen stimulation, prolactin stimulation did not modulate kisspeptin, NKB, or DynA protein expression in these cells. Conclusions Our observations imply that hyperandrogenemia affects KNDy neurons and changes their neuronal characteristics by increasing kisspeptin and NKB levels and decreasing DynA levels. These changes might cause dysfunction of the hypothalamic–pituitary–gonadal axis.

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“…Findings of this study showed that under the influence of estradiol along with RFRP‐3 expression, both NT and CRH had inhibitory effects on Kiss‐1 gene expression in the ARC kisspeptin neurons. 34 Thus we can assume that during non‐breeding season greater RFRP‐3 expression might enhance the NT and CRH expression both of which may inhibit kiss‐1 gene function reducing kisspeptin to GnRH, resulting in reproductive axis suppression.…”

Section: Discussionmentioning

confidence: 99%

“…Our result of co-localization is consistent with a recent study, that found Furthermore, previous research showed that the hypothalamic ARC cell model (mHypoA-55) expressed kisspeptin, neurotensin (NT), corticotrophins-releasing hormone (CRH), and RFRP-3. 34 NT, a neuropeptide, notably express in AVPV and ARC area of mammals and has been shown to involved in feeding and reproductive functions. Similarly, CRH is largely synthesized in paraventricular nucleus and involved as a key processor for stress responses.…”

Section: Discussionmentioning

confidence: 99%

Expression and co‐localization of RFRP‐3 and kisspeptin during breeding and non‐breeding season in the hypothalamus of male rhesus monkey (Macaca mulatta)

Khan

Batool

Zubair

et al. 2022

Reprod Medicine & Biology

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Propose The mechanism that underpins how RFRP‐3 and kisspeptin interacts are not fully understood in higher primates. This study therefore set out to assess RFRP‐3 and kisspeptin expression and their morphological interactions in the breeding, and in the non‐breeding period in monkey hypothalamus. Methods Eight mature male macaques ( Macaca mulatta ) in the breeding season (February; n = 4) and non‐breeding season (June; n = 4) were used. To reveal the expression and co‐localization of RFRP‐3 and kisspeptin, double‐labeled immunohistochemistry was performed. Testicular volume, sperm count, and plasma testosterone level were also measured to validate the breeding and non‐breeding paradigms. Results Testicular volume, plasma testosterone level, and sperm count showed a significant reduction during non‐breeding season. The number of kisspeptin‐positive cells was significantly increased during the breeding season ( p < 0.05), whereas more RFRP‐3‐positive cell bodies were seen in the non‐breeding season ( p < 0.01). Close contacts of RFRP‐3 fibers with kisspeptin cells showed no significant difference ( p > 0.05) across seasons. However, co‐localization of RFRP‐3‐ir cell bodies onto kisspeptin IR cell bodies showed a statistical increase ( p < 0.01) in non‐breeding season. Conclusion In higher primates, RFRP‐3 decreases kisspeptin drives from the same cells to GnRH neurons in an autocrine manner causing suppression of the reproductive axis during the non‐breeding period.

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Action of neurotensin, corticotropin-releasing hormone, and RFamide-related peptide-3 in E2-induced negative feedback control: studies using a mouse arcuate nucleus hypothalamic cell model†

Cited by 14 publications

References 52 publications

Functional Implications of RFRP-3 in the Central Control of Daily and Seasonal Rhythms in Reproduction

Functional Implications of RFRP-3 in the Central Control of Daily and Seasonal Rhythms in Reproduction

Hyperandrogenism induces proportional changes in the expression of Kiss-1, Tac2, and DynA in hypothalamic KNDy neurons

Expression and co‐localization of RFRP‐3 and kisspeptin during breeding and non‐breeding season in the hypothalamus of male rhesus monkey (Macaca mulatta)

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