Article

Influence of Age and 17β-Estradiol on Kisspeptin, Neurokinin B, and Prodynorphin Gene Expression in the Arcuate-Median Eminence of Female Rhesus Macaques

Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon 97006, USA.
Endocrinology (Impact Factor: 4.5). 08/2010; 151(8):3783-94. DOI: 10.1210/en.2010-0198
Source: PubMed

ABSTRACT

The neuropeptides kisspeptin, neurokinin B, and dynorphin A (collectively abbreviated as KNDy) are, respectively, encoded by KiSS-1, NKB, and PDYN and are coexpressed by neurons of the hypothalamic arcuate nucleus (ARC). Here, using quantitative real-time PCR, we examined age-related changes in the expression of genes encoding KNDy and associated receptors G protein-coupled receptor 54 (encoded by GPR54), neurokinin 3 receptor (encoded by NK3), and kappa-opioid receptor (encoded by KOR), in the female rhesus macaque ARC-median eminence (ARC-ME). Expression of KiSS-1 and NKB was highly elevated in old perimenopausal compared with young or middle-aged premenopausal animals. To test whether these age-related changes could be attributed to perimenopausal loss of sex steroids, we then examined KNDy, GPR54, NK3, and KOR expression changes in response to ovariectomy (OVX) and exposure to 17beta-estradiol (E(2)). Short-term (7 months) OVX (with or without 1 month of estrogen replacement) failed to modulate the expression of any of the KNDy-related genes. In contrast, long-term ( approximately 4 yr) OVX significantly increased KiSS-1 and NKB expression, and this was reversed by E(2) administration. Finally, we examined the expression of KNDy-related genes in young adult females during the early follicular, late follicular, or midluteal phases of their menstrual cycle but found no difference. Together, the results suggest that short-term alterations in circulating E(2) levels, such as those occurring during the menstrual cycle, may have little effect on the ARC-ME expression of KNDy and associated receptors. Nevertheless, they clearly demonstrate that loss of ovarian steroid negative feedback that occurs during perimenopause plays a major role in modulating the activity of KNDy circuits of the aging primate ARC-ME.

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Available from: Dominique Eghlidi
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    • "Notably, no changes in the POA have yet been reported across monkey physiology. With aging, Kiss1 and GPR54 mRNA levels increase in the mediobasal hypothalamus but remain unchanged in the POA (Kim et al., 2009; Eghlidi et al., 2010). By analogy, LH pulsatile secretion increases in aging monkeys but these are still able to generate GnRH/LH surges (Gore et al., 2004). "
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    ABSTRACT: The prominent role of the G protein coupled receptor GPR54 and its peptide ligand kisspeptin in the progression of puberty has been extensively documented in many mammalian species including humans. Kisspeptins are very potent gonadotropin-releasing hormone secretagogues produced by two main populations of neurons located in two ventral forebrain regions, the preoptic area and the arcuate nucleus. Within the last 2 years a substantial amount of data has accumulated concerning the development of these neuronal populations and their timely regulation by central and peripheral factors during fetal, neonatal, and peripubertal stages of development. This review focuses on the development of the kisspeptin-GPR54 system in the brain of female mice, rats, sheep, monkeys, and humans. We will also discuss the notion that this system represents a major target through which signals from the environment early in life can reprogram reproductive function.
    Full-text · Article · Mar 2013 · Frontiers in Endocrinology
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    • "Notably, no changes in the POA have yet been reported across monkey physiology. With aging, Kiss1 and GPR54 mRNA levels increase in the mediobasal hypothalamus but remain unchanged in the POA (Kim et al., 2009; Eghlidi et al., 2010). By analogy, LH pulsatile secretion increases in aging monkeys but these are still able to generate GnRH/LH surges (Gore et al., 2004). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The prominent role of the G protein coupled receptor GPR54 and its peptide ligand kisspeptin in the progression of puberty has been extensively documented in many mam-malian species including humans. Kisspeptins are very potent gonadotropin-releasing hormone secretagogues produced by two main populations of neurons located in two ventral forebrain regions, the preoptic area and the arcuate nucleus. Within the last 2 years a substantial amount of data has accumulated concerning the development of these neu-ronal populations and their timely regulation by central and peripheral factors during fetal, neonatal, and peripubertal stages of development.This review focuses on the development of the kisspeptin–GPR54 system in the brain of female mice, rats, sheep, monkeys, and humans. We will also discuss the notion that this system represents a major target through which signals from the environment early in life can reprogram reproductive function.
    Full-text · Dataset · Mar 2013
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    • "nkey studies have been performed in males , and whether Kiss1 or kisspeptin neurons in the POA region of monkeys are more readily detectable in females remains to be addressed . As in rodents and sheep , sex steroids can regulate the neuronal expression of kisspeptin in monkeys , with E2 and T suppressing Kiss1 levels in the infundibular nucleus ( Eghlidi et al . , 2010 ; Rome - to et al . , 2007 ; Shibata et al . , 2007 ) . An additional similarity be - tween monkeys and other mammals is that the infundibular population of kisspeptin neurons co - expresses NKB and dynorphin ( Ramaswamy et al . , 2010 ) . To date , kisspeptin or Kiss1 expression has yet to be reported in the MeA of sheep or monkeys . 4"
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    ABSTRACT: Kisspeptin, encoded by the Kiss1 gene, is a neuropeptide required for puberty and adult reproductive function. Understanding the regulation and development of the kisspeptin system provides valuable knowledge about the physiology of puberty and adult fertility, and may provide insights into human pubertal or reproductive disorders. Recent studies, particularly in rodent models, have assessed how kisspeptin neurons develop and how hormonal and non-hormonal factors regulate this developmental process. Exposure to sex steroids (testosterone and estradiol) during critical periods of development can induce organizational (permanent) effects on kisspeptin neuron development, with respect to both sexually dimorphic and non-sexually dimorphic aspects of kisspeptin biology. In addition, sex steroids can also impart activational (temporary) effects on kisspeptin neurons and Kiss1 gene expression at various times during neonatal and peripubertal development, as they do in adulthood. Here, we discuss the current knowledge-and in some cases, lack thereof-of the influence of hormones and other factors on kisspeptin neuronal development.
    Full-text · Article · Jun 2012 · Frontiers in Neuroendocrinology
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