Influence of age and 17beta-estradiol on kisspeptin, neurokinin B, and prodynorphin gene expression in the arcuate-median eminence of female rhesus macaques.
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.
Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon 97006, USA.
Dominique H
DH
Eghlidi
Gwendolen E
GE
Haley
Nigel C
NC
Noriega
Steven G
SG
Kohama
Henryk F
HF
Urbanski
D000367:Age Factors; D000375:Aging / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004745:Enkephalins / Q000235:genetics* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D016147:Genes, Tumor Suppressor / Q000187:drug effects; D008253:Macaca mulatta; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D015287:Neurokinin B / Q000235:genetics* / Q000378:metabolism; D010052:Ovariectomy; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D004745:Enkephalins; D011498:Protein Precursors; D043562:Receptors, G-Protein-Coupled; D004958:Estradiol; D015287:Neurokinin B; C033660:preproenkephalin