Hypothalamic Expression of KISS1 and Gonadotropin Inhibitory Hormone Genes During the Menstrual Cycle of a Non-Human Primate1

Smith, Jeremy Troy; Shahab, Muhammad; Pereira, Alda; Pau, K.-Y. Francis; Clarke, I. J.

doi:10.1095/biolreprod.110.085407

Cited by 120 publications

(126 citation statements)

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“…The greatest extent of RFRP-3/GnRH fiber colocalization was observed in the ME, where dense GnRH fiber networks were present in the external layer. Although heavy RFRP-ir was seen in the internal layer, projections to the external zone were scarce, suggesting limited hypophysiotrophism as in other mammalian species (14,16,27,(48)(49)(50)(51). Rather than acting on both the pituitary and GnRH neurons as its avian ortholog does (11,13,52,53), it is likely that RFRP-3 acts directly only on GnRH neurons to inhibit NMR reproductive function.…”

Section: Discussionmentioning

confidence: 94%

RFamide-related peptide-3 (RFRP-3) suppresses sexual maturation in a eusocial mammal

Peragine

Pokarowski

Mendoza-Viveros

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Neuroendocrine mechanisms underlying social inhibition of puberty are not well understood. Here, we use a model exhibiting the most profound case of pubertal suppression among mammals to explore a role for RFamide-related peptide-3 [RFRP-3; mammalian ortholog to gonadotropin-inhibitory hormone (GnIH)] in neuroendocrine control of reproductive development. Naked mole rats (NMRs) live in sizable colonies where breeding is monopolized by two to four dominant animals, and no other members exhibit signs of puberty throughout their lives unless they are removed from the colony. Because of its inhibitory action on the reproductive axis in other vertebrates, we investigated the role of RFRP-3 in social reproductive suppression in NMRs. We report that RFRP-3 immunofluorescence expression patterns and RFRP-3/GnRH cross-talk are largely conserved in the NMR brain, with the exception of the unique presence of RFRP-3 cell bodies in the arcuate nucleus (Arc). Immunofluorescence comparisons revealed that central expression of RFRP-3 is altered by reproductive status, with RFRP-3 immunoreactivity enhanced in the paraventricular nucleus, dorsomedial nucleus, and Arc of reproductively quiescent NMRs. We further observed that exogenous RFRP-3 suppresses gonadal steroidogenesis and mating behavior in NMRs given the opportunity to undergo puberty. Together, our findings establish a role for RFRP-3 in preserving reproductive immaturity, and challenge the view that stimulatory peptides are the ultimate gatekeepers of puberty.eusocial | GnIH | naked mole rat | puberty | RFRP-3

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Section: Discussionmentioning

confidence: 94%

RFamide-related peptide-3 (RFRP-3) suppresses sexual maturation in a eusocial mammal

Peragine

Pokarowski

Mendoza-Viveros

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Rometo et al (610) showed that the estrogenic feedback effect also occurs in women by demonstrating 1) that the increases in GnRH secretion that occurs in postmenopausal women and in ovariectomized cynomolgus macaques (Macaca fascicularis) were associated with increased kisspeptin expression in the arcuate nucleus, and 2) that in ovariectomized monkeys estradiol treatment reversed both effects. In another interesting study (682), kisspeptin mRNA expression in the preoptic area and caudal arcuate nucleus and GnIH mRNA expression in the dorsal medial and paraventricular nuclei were higher in the follicular than the luteal phases of rhesus macaques (Macaca mulatta).…”

Section: Physiological Sex Differences In Disordered Eating)mentioning

confidence: 92%

“…In one study, GnIH was found in the arcuate nucleus in women and female cynomolgus macaques (610); in another study, it was found in the intermediate periventricular (which is adjacent to the dorsomedial nucleus) and paraventricular nuclei in female rhesus macaques (746); and in a third study, it was found in the arcuate, dorsomedial and intermediate periventricular nuclei of female rhesus macaques (682). Interestingly, in the latter study, kisspeptin mRNA expression in the preoptic area and arcuate nucleus and GnIH mRNA expression in the dorsomedial and paraventricular nuclei were higher in the follicular phase than in the luteal phase (682). GnIH fibers project to similar areas as the GnRH neurons, as well as several other brain areas (127,407,745).…”

Section: Physiological Sex Differences In Disordered Eating)mentioning

confidence: 96%

“…Central administration of kisspeptin inhibited eating in male mice (692), and central administration of GnIH stimulated eating in male mice, rats, and cynomolgus monkeys (127,352,498,682). In addition, in female rats, knockdown of Arc kisspeptin neurons with saporin conjugated to the neurokinin-3 receptor, which the Arc kisspeptin neurons also express, reduced the effect of ovariectomy to increase body weight; unfortunately food intake was not measured (487).…”

Section: Physiological Sex Differences In Disordered Eating)mentioning

confidence: 99%

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Sex differences in the physiology of eating

Asarian

Geary²

2013

American Journal of Physiology-Regulatory, Integrative and Comp

408

363

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(HPG) axis function fundamentally affects the physiology of eating. We review sex differences in the physiological and pathophysiological controls of amounts eaten in rats, mice, monkeys, and humans. These controls result from interactions among genetic effects, organizational effects of reproductive hormones (i.e., permanent early developmental effects), and activational effects of these hormones (i.e., effects dependent on hormone levels). Male-female sex differences in the physiology of eating involve both organizational and activational effects of androgens and estrogens. An activational effect of estrogens decreases eating 1) during the periovulatory period of the ovarian cycle in rats, mice, monkeys, and women and 2) tonically between puberty and reproductive senescence or ovariectomy in rats and monkeys, sometimes in mice, and possibly in women. Estrogens acting on estrogen receptor-␣ (ER␣) in the caudal medial nucleus of the solitary tract appear to mediate these effects in rats. Androgens, prolactin, and other reproductive hormones also affect eating in rats. Sex differences in eating are mediated by alterations in orosensory capacity and hedonics, gastric mechanoreception, ghrelin, CCK, glucagon-like peptide-1 (GLP-1), glucagon, insulin, amylin, apolipoprotein A-IV, fatty-acid oxidation, and leptin. The control of eating by central neurochemical signaling via serotonin, MSH, neuropeptide Y, Agouti-related peptide (AgRP), melanin-concentrating hormone, and dopamine is modulated by HPG function. Finally, sex differences in the physiology of eating may contribute to human obesity, anorexia nervosa, and binge eating. The variety and physiological importance of what has been learned so far warrant intensifying basic, translational, and clinical research on sex differences in eating.neuroendocrinology; estrogens; testosterone; eating disorders; obesity SEX DIFFERENCES ARE PERVASIVE in physiology and medicine (51,64,73,109,110,466,797,826). The controls of eating and energy homeostasis are no exceptions. It was observed approximately 100 years ago that removal of the ovaries leads to marked accretion of adipose tissue in rats (697), that daily food intake expressed as kilocalories per gram body weight differs between male and female rats (778), and that food intake varies regularly through the ovarian cycle in intact female rats (674, 779). Sex differences in eating have been the subject of physiological research ever since. The clinical relevance of this work is increasingly evident. In the United States, women are approximately threefold more vulnerable than men to psychiatric eating disorders (346,351) and approximately twofold more vulnerable to severe and morbid obesity (BMI Ն 35 and 40 kg/m 2 , respectively, mass/height 2 ) (226). Women also appear to suffer more from these disorders in terms of physical and psychological functioning and quality of life (24,84,273,292,465,531,762). The increased obesity burden suffered by women is reflected in the fact that Ͼ80% of bariatric surgery patients in the U...

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“…Primates may have a surge-generating mechanism different from that in rodents. The mediobasal hypothalamus might play a crucial role in surge induction (13,14).…”

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confidence: 99%

Epigenetic regulation of Kiss1 gene expression mediating estrogen-positive feedback action in the mouse brain

Tomikawa¹,

Uenoyama²,

Ozawa³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

130

118

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This study aims to determine the epigenetic mechanism regulating Kiss1 gene expression in the anteroventral periventricular nucleus (AVPV) to understand the mechanism underlying estrogen-positive feedback action on gonadotropin-releasing hormone/gonadotropin surge. We investigated estrogen regulation of the epigenetic status of the mouse AVPV Kiss1 gene locus in comparison with the arcuate nucleus (ARC), in which Kiss1 expression is down-regulated by estrogen. Histone of AVPV Kiss1 promoter region was highly acetylated, and estrogen receptor α was highly recruited at the region by estrogen. In contrast, the histone of ARC Kiss1 promoter region was deacetylated by estrogen. Inhibition of histone deacetylation upregulated in vitro Kiss1 expression in a hypothalamic non-Kiss1-expressing cell line. Gene conformation analysis indicated that estrogen induced formation of a chromatin loop between Kiss1 promoter and the 3′ intergenic region, suggesting that the intergenic region serves to enhance estrogen-dependent Kiss1 expression in the AVPV. This notion was proved, because transgenic reporter mice with a complete Kiss1 locus sequence showed kisspeptin neuronspecific GFP expression in both the AVPV and ARC, but the deletion of the 3′ region resulted in greatly reduced GFP expression only in the AVPV. Taken together, these results demonstrate that estrogen induces recruitment of estrogen receptor α and histone acetylation in the Kiss1 promoter region of the AVPV and consequently enhances chromatin loop formation of Kiss1 promoter and Kiss1 gene enhancer, resulting in an increase in AVPV-specific Kiss1 gene expression. These results indicate that epigenetic regulation of the Kiss1 gene is involved in estrogen-positive feedback to generate the gonadotropin-releasing hormone/gonadotropin surge.

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Hypothalamic Expression of KISS1 and Gonadotropin Inhibitory Hormone Genes During the Menstrual Cycle of a Non-Human Primate1

Cited by 120 publications

References 72 publications

RFamide-related peptide-3 (RFRP-3) suppresses sexual maturation in a eusocial mammal

RFamide-related peptide-3 (RFRP-3) suppresses sexual maturation in a eusocial mammal

Sex differences in the physiology of eating

Epigenetic regulation of Kiss1 gene expression mediating estrogen-positive feedback action in the mouse brain

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