Kisspeptin Induces Dynamic Chromatin Modifications to Control GnRH Gene Expression

Novaira, Horacio J.; Sonko, Momodou L.; Radovick, Sally

doi:10.1007/s12035-015-9269-0

Cited by 14 publications

(6 citation statements)

References 63 publications

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“…In addition, GT1-7 cells treated with kisspeptin significantly increased total histone 3 acetylation (H3Ac). It demonstrated an histonedependent transcription activation and chromatin conformation mediated by kisspeptin [19].…”

Section: Cellular Physiology and Biochemistry Cellular Physiology Andmentioning

confidence: 98%

Kisspeptin/GPR54 System: What Do We Know About Its Role in Human Reproduction?

Trevisan

Montagna

Oliveira

et al. 2018

Cell Physiol Biochem

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Kisspeptin is involved in the control of human reproduction bridging the gap between the sex steroid levels and feedback mechanisms that control the gonadotropin releasing hormone (GnRH) secretion; however, studies considering this peptide and infertility are limited. We conducted a review and critical assessment of available evidence considering kisspeptin structure, physiology, function in puberty and reproduction, its role in assisted reproduction treatments, kisspeptin dosage and the impact on KISS1 and GPR54 genes. Literature searches were conducted in PubMed using keywords related to: (i) kisspeptin or receptors, kisspeptin-1 (ii) reproduction or infertility or fertility (iii) gene and (iv) dosage or measurement or quantification or serum level, in human. Kisspeptin is a product of KISS1 gene that binds to a G-protein-coupled receptor (GPR54/KISS1R) stimulating the release of GnRH by hypothalamic neurons, leading to secretion of pituitary gonadotropins (LH and FSH) and sexual steroids, which in turn will act in the gonads to produce the gametes. Kisspeptin is being recognized as a crucial regulator of the onset of puberty, the regulation of sex hormone mediated secretion of gonadotropins, and the control of fertility. Inactivating and activating mutations in both KISS1 or GPR54 genes were associated with hypogonadotropic hypogonadism and precocious puberty. Despite this, studies considering kisspeptin and infertility are scarce. The understanding of the role of kisspeptin may lead to its use as a biomarker in infertility treatments and use in controlled ovarian hyperstimulation.

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Section: Cellular Physiology and Biochemistry Cellular Physiology Andmentioning

confidence: 98%

Kisspeptin/GPR54 System: What Do We Know About Its Role in Human Reproduction?

Trevisan

Montagna

Oliveira

et al. 2018

Cell Physiol Biochem

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show abstract

“…Numerous studies have described the presence and pivotal role of Kp and GPR54 in the hypothalamus (28)(29)(30)(31). Furthermore, in several species, including humans, peripheral administration of Kp is known to stimulate GnRH release in the hypothalamus (1,29,(32)(33)(34)(35)(36)(37)(38). All of these studies demonstrate that the Kp-GPR54 system plays an important role in pubertal maturation, reproduction and GnRH release.…”

Section: Discussionmentioning

confidence: 98%

Aging reduces kisspeptin receptor (GPR54) expression levels in the hypothalamus and extra‑hypothalamic brain regions

et al. 2021

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Aging leads to the diminished pulsatile secretion of hypothalamic gonadotropin-releasing hormone (GnRH). Kisspeptin (Kp), the upstream regulator of the hypothalamic-pituitary-gonadal (HPG) axis, regulates GnRH synthesis and release through its cognate receptor, G-protein coupled receptor 54 (GPR54). In turn, GnRH regulates GPR54 expression. GnRH administration into the third ventricle has been shown to induce neurogenesis in different brain regions in old age. However, aging-associated changes in hypothalamic and extra-hypothalamic GPR54 expression were unclear. Therefore, the expression levels of GPR54 were evaluated in various brain regions of adult (age, 3-4 months) and old (age, 20-24 months) male Wistar rats in the present study. In the hypothalamus, mRNA and protein levels of Kp and GPR54 were identified to be significantly decreased in old age. Furthermore, GnRH1 expression in the hypothalamus was analyzed to observe the functional consequence of a reduced Kp-GPR54 system in the hypothalamus. It was found that hypothalamic GnRH1 levels were significantly decreased in old age. As GnRH regulates GPR54 levels, GPR54 was examined in extra-hypothalamic regions. GPR54 levels were found to be significantly decreased in the hippocampus and medulla and pons in old-age rats when compared to adult rats. Notably, GPR54 expression was observed in the frontal lobe, cortex, midbrain and cerebellum of adult and old-age rats; however, the difference between the two groups was not statistically significant. To the best of our knowledge, this is the first study that provides the quantitative distribution of GPR54 in different brain regions during aging. Thus, the reduced levels of Kp and its receptor, GPR54 in the hypothalamus could be cumulatively responsible for reduced levels of GnRH observed in old age.

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“…EHMT1 methylates H3K9 in euchromatin, resulting in epigenetic transcriptional repression [ 4 ]. EHMT1 regulates transcription through methylation; furthermore, kisspeptin, a neuropeptide that plays a key role in gonadal development [ 12 ], also regulates GnRH neuron expression through histone acetylation/methylation [ 13 , 14 ]. Thus, a mutation in EHMT1 could repress transcription of the GnRH gene through histone methylation defect and epigenetic dysregulation.…”

Section: Discussionmentioning

confidence: 99%

A Korean male with Kleefstra syndrome presented with micropenis

Lee,

Moon

2023

Ann Pediatr Endocrinol Metab

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Kleefstra syndrome is caused by chromosome 9q34.3 deletion or heterozygous mutations in the euchromatin histone methyl transferase 1 (EHMT1) gene. It can be accompanied by intellectual disability, distinctive facial features, microcephaly, psychiatric disorders, hypotonia in childhood, hearing loss, heart defects, renal defects, epilepsy, speech anomalies, and obesity. Furthermore, genital anomalies are present in 30%–40% of male patients with Kleefstra syndrome, but their mechanisms have not been elucidated. Herein, we report a patient with Kleefstra syndrome presenting with micropenis. The patient was transferred to Kyungpook National University Children's Hospital for management of imperforate anus on the day of birth. Physical examination revealed micropenis with stretched penile length of 0.9 cm and facial dysmorphisms, including hypertelorism and anteverted nares. Chromosomal microarray revealed 424-kb heterozygous deletion at chromosome 9q34.3 (arr[hg19] 9q34.3 (140,234,315-140,659,055)x1). Among the involved main OMIM genes, phenotypically relevant genes were EHMT1 and NSMF. Endocrinological investigation showed low basal gonadotropin and testosterone levels. Anterior pituitary hormones and steroid hormone levels were in the normal range. Testicular function was normal based on human chorionic gonadotropin stimulation test. The patient experienced improvement in penile length growth with intramuscular testosterone enanthate injection initiated at 4 months of age. The purpose of this study is to describe the etiology, endocrine laboratory tests, and treatment of micropenis in Kleefstra syndrome.

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Kisspeptin Induces Dynamic Chromatin Modifications to Control GnRH Gene Expression

Cited by 14 publications

References 63 publications

Kisspeptin/GPR54 System: What Do We Know About Its Role in Human Reproduction?

Kisspeptin/GPR54 System: What Do We Know About Its Role in Human Reproduction?

Aging reduces kisspeptin receptor (GPR54) expression levels in the hypothalamus and extra‑hypothalamic brain regions

A Korean male with Kleefstra syndrome presented with micropenis

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