title: Age-related alterations in hypothalamic kisspeptin, neurokinin B, and dynorphin neurons and in pulsatile LH release in female and male rats.
abstract: Pulsatile secretion of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) decreases during aging. Kisspeptin (encoded by Kiss1) neurons in the arcuate nucleus coexpress neurokinin B (Tac3) and dynorphin (Pdyn) and are critical for regulating the GnRH/LH pulse. We therefore examined kisspeptin neurons by histochemistry and pulsatile LH release in rats aged 2-3 (Young), 12-13 (Young-Middle), 19-22 (Late-Middle), and 24-26 (Old) months. Total LH concentrations, sampled for 3 hours, decreased in both sexes with aging. In females, numbers of Tac3 and Pdyn neurons were significantly reduced in all aging rats, and numbers of Kiss1 neurons were significantly reduced in Late-Middle and Old rats. In males, numbers of all 3 neuron-types were significantly decreased in all aging rats. GnRH agonist induced LH release in all animals; however, the increased LH concentration in all aging rats was less than that in Young rats. These results suggest that expression of each gene in kisspeptin neurons may be controlled individually during aging, and that reduction of their expression or change in pituitary responsiveness may cause attenuated pulsatile LH secretion.
authors.affiliation: Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Yuyu
authors.initials: Y
authors.lastname: Kunimura
authors.affiliation: Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Kinuyo
authors.initials: K
authors.lastname: Iwata
authors.affiliation: Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Ishigami
authors.affiliation: Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. Electronic address: hozawa@nms.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ozawa
mesh_terms: D000375:Aging / Q000473:pathology* / Q000502:physiology*; D000818:Animals; D004399:Dynorphins / Q000378:metabolism* / Q000502:physiology; D005260:Female; D006651:Histocytochemistry; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D059648:Kisspeptins / Q000378:metabolism* / Q000502:physiology; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D008593:Menopause / Q000378:metabolism / Q000502:physiology; D015287:Neurokinin B / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology* / Q000502:physiology; D011673:Pulsatile Flow; D017208:Rats, Wistar
chemical_list: D059648:Kisspeptins; D004399:Dynorphins; D015287:Neurokinin B; D007986:Luteinizing Hormone
keywords: Aging; KNDy neuron; Menopause; Pulse generator; Reproduction