Direct Regulation of Gonadotrophin‐Releasing Hormone (GnRH) Transcription By RF‐Amide‐Related Peptide‐3 and Kisspeptin in A Novel GnRH‐Secreting Cell Line, mHypoA‐GnRH/GFP

Gojska, Nicole; Friedman, Zoey; Belsham, Denise D.

doi:10.1111/jne.12225

Cited by 23 publications

(8 citation statements)

References 55 publications

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“…This finding suggests that GnIH might be involved in central inhibition by restraining pulsatile secretion of GnRH during the prepubertal period. This hypothesis is supported by evidence that GPR147 is expressed on GnRH neurons [ 36 , 37 ]. Furthermore, administration of GnIH or its mammalian ortholog, RFRP3, has been reported to result in inhibition of GnRH secretion [ 9 , 38 – 40 ].…”

Section: Discussionmentioning

confidence: 77%

Dynamic Regulation of Hypothalamic DMXL2, KISS1, and RFRP Expression During Postnatal Development in Non-Human Primates

et al. 2016

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The neurobiological mechanism of puberty onset in primates is currently only partly understood. A recent study reported an important role of Dmx-like 2 (DMXL2), a gene encoding rabconnectin-3α vesicular protein, in human subjects with mental retardation and neuroendocrine impairment of reproduction. To further characterize the potential role of DMXL2 in the regulation of reproduction, we analyzed the expression of DMXL2 in hypothalami of newborn, infantile, juvenile, pubertal, and postpubertal female and male common marmoset monkeys. Additionally, as the relative hypothalamic levels of gonadotropin-inhibitory hormone (GnIH) transcript during postnatal development are unknown in primates, we also quantified messenger RNA (mRNA) levels of RFRP, a gene encoding GnIH. Moreover, the transcript levels of kisspeptin, a well-known regulator of the hypothalamic neurohormonal axis controlling reproduction, were also checked. Transcript and protein levels of DMXL2 and Kiss1 transcript levels increase from the newborn to the infantile and from the juvenile (prepubertal) to the pubertal and the postpubertal period. We also noted a clear upsurge in RFRP transcript levels in the prepubertal period. In conclusion, the hypothalamic expressions of Kiss1 and DMXL2 mRNA increase during infantile, pubertal, and adult stages compared to newborn and juvenile stages in common marmoset monkeys. In contrast, the expression of RFRP mRNA upsurges in juvenile monkeys. Further mechanistic studies are needed to characterize the potential inhibitory role of the GnIH-GPR147 signaling in the prepubertal period and the role of DMXL2 in the molecular cascade regulating the neuroendocrine reproductive axis in primates.Electronic supplementary materialThe online version of this article (doi:10.1007/s12035-016-0329-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 77%

Dynamic Regulation of Hypothalamic DMXL2, KISS1, and RFRP Expression During Postnatal Development in Non-Human Primates

et al. 2016

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“…GnIH (RFRP3) also suppresses the firing of kisspeptin‐activated vGluT2 (vesicular glutamate transporter 2)‐GnRH neurons as well as of kisspeptin‐insensitive GnRH neurons . Suppression of GnRH mRNA expression by GnIH (RFRP3) administration was also shown in a novel GnRH neuronal cell model, mHypoA‐GnRH/GFP . Accordingly, GnIH may inhibit the secretion of gonadotropins by decreasing the activity of GnRH neurons in addition to directly regulating pituitary gonadotropin secretion.…”

Section: Regulation Of Gonadotropin Synthesis and Releasementioning

confidence: 91%

Reproductive neuroendocrinology of mammalian gonadotropin‐inhibitory hormone

Ubuka

Tsutsui

2019

Reprod Medicine & Biology

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Background Gonadotropin‐inhibitory hormone (GnIH) was discovered in the Japanese quail brain in 2000 as a hypothalamic neuropeptide that suppresses luteinizing hormone release from cultured quail anterior pituitary. Methods The authors investigated the existence of mammalian orthologous peptides to GnIH and their physiological functions in the following 19 years of research. Main findings Mammals have orthologous peptide to GnIH, often described RFamide‐related peptide, expressed in the hypothalamus and gonads. Mammalian GnIH may also suppress gonadotropin synthesis and release by suppressing gonadotropin‐releasing hormone (GnRH) synthesis and release in addition to directly suppressing gonadotropin synthesis and release from the pituitary. Mammalian GnIH may also suppress kisspeptin, a stimulator of GnRH, release. Mammalian GnIH is also expressed in the testis and ovary and suppresses gametogenesis and sex steroid production acting in an autocrine/paracrine manner. Thus, mammalian GnIH may act at all levels of the hypothalamic‐pituitary‐gonadal axis to suppress reproduction. GnIH may be involved in the regulation of puberty, estrous or menstrual cycle, seasonal reproduction, and stress responses. Conclusion Studies suggest that mammalian GnIH is an important neuroendocrine suppressor of reproduction in mammals.

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“…A study using another GnRH neuronal cell model, mHypoA-GnRH/GFP, generated from adult-derived GnRH-GFP neurons, shows the interaction of GnIH and kisspeptin on GnRH transcriptional regulation (65). In mHypoA-GnRH/GFP cells, treatment of GnIH attenuates basal GnRH mRNA expression, whereas kisspeptin induces GnRH levels.…”

Section: Potential Signaling Pathways That Convey the Inhibitory Actimentioning

confidence: 99%

“…Co-treatment of GnIH and kisspeptin suppresses GnRH mRNA expression, suggesting the inhibitory effect of GnIH may override the stimulatory effect of kisspeptin on GnRH mRNA expression. By using transcriptional inhibitors (actinomycin D and DRB), Gojska et al further show that GnIH-mediated repression is involved in new RNA synthesis rather than affecting the stability of pre-existing GnRH mRNA in mHypoA-GnRH/GFP cells (65). Although they present a novel action mechanism of GnIH on GnRH transcriptional regulation, these results do not indicate the direct inhibitory effect of GnIH on kisspeptin-induced signaling pathway.…”

Section: Potential Signaling Pathways That Convey the Inhibitory Actimentioning

confidence: 99%

Molecular Mechanisms of Gonadotropin-Inhibitory Hormone (GnIH) Actions in Target Cells and Regulation of GnIH Expression

2019

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Since gonadotropin-inhibitory hormone (GnIH) was discovered in 2000 as the first hypothalamic neuropeptide that actively inhibits gonadotropin release, researches conducted for the last 18 years have demonstrated that GnIH acts as a pronounced negative regulator of reproduction. Inhibitory effect of GnIH on reproduction is mainly accomplished at hypothalamic-pituitary levels; gonadotropin-releasing hormone (GnRH) neurons and gonadotropes are major targets of GnIH action based on the morphological interaction with GnIH neuronal fibers and the distribution of GnIH receptor. Here, we review molecular studies mainly focusing on the signal transduction pathway of GnIH in target cells, GnRH neurons, and gonadotropes. The use of well-defined cellular model systems allows the mechanistic study of signaling pathway occurring in target cells by demonstrating the direct cause-and-effect relationship. The insights gained through studying molecular mechanism of GnIH action contribute to deeper understanding of the mechanism of how GnIH communicates with other neuronal signaling systems to control our reproductive function. Reproductive axis closely interacts with other endocrine systems, thus GnIH expression levels would be changed by adrenal and thyroid status. We also briefly review molecular studies investigating the regulatory mechanisms of GnIH expression to understand the role of GnIH as a mediator between adrenal, thyroid and gonadal axes.

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Direct Regulation of Gonadotrophin‐Releasing Hormone (GnRH) Transcription By RF‐Amide‐Related Peptide‐3 and Kisspeptin in A Novel GnRH‐Secreting Cell Line, mHypoA‐GnRH/GFP

Cited by 23 publications

References 55 publications

Dynamic Regulation of Hypothalamic DMXL2, KISS1, and RFRP Expression During Postnatal Development in Non-Human Primates

Dynamic Regulation of Hypothalamic DMXL2, KISS1, and RFRP Expression During Postnatal Development in Non-Human Primates

Reproductive neuroendocrinology of mammalian gonadotropin‐inhibitory hormone

Molecular Mechanisms of Gonadotropin-Inhibitory Hormone (GnIH) Actions in Target Cells and Regulation of GnIH Expression

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