title: Klotho and the Growth Hormone/Insulin-Like Growth Factor 1 Axis: Novel Insights into Complex Interactions.
abstract: The growth hormone (GH)/insulin-like growth factor (IGF)-1 axis is pivotal for many metabolic functions, including proper development and growth of bones, skeletal muscles, and adipose tissue. Defects in the axis' activity during childhood result in growth abnormalities, while increased secretion of GH from the pituitary results in acromegaly. In order to keep narrow physiologic concentration, GH and IGF-1 secretion and activity are tightly regulated by hypothalamic, pituitary, endocrine, paracrine, and autocrine factors. Klotho was first discovered as an aging-suppressor gene. Mice that do not express klotho die prematurely with multiple symptoms of aging, several of them are also characteristic of decreased GH/IGF-1 axis activity. Klotho is highly expressed in the brain, the kidney, and parathyroid and pituitary glands, but can also serve as a circulating hormone by its shedding, forming soluble klotho that can be detected in blood, cerebrospinal fluid, and urine. Several lines of evidence suggest an association between klotho levels and activity of the GH/IGF-1 axis: the GH-secreting cells in the anterior pituitary of klotho-deficient mice are hypotrophic; klotho levels are altered in subjects with pathologies of the GH/IGF-1 axis; and accumulating data indicate that klotho is a direct regulator of GH secretion. Thus, klotho seems to be a new player in the intricate regulation of the GH/IGF-1 axis.
authors.affiliation: Institute of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. Electronic address: rubinekt@gmail.com.
authors.forename: T
authors.initials: T
authors.lastname: Rubinek
authors.affiliation: The Edmond and Lily Safra Children's Hospital, Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel; Tel Aviv University, Tel Aviv, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Modan-Moses
mesh_terms: D000172:Acromegaly; D000375:Aging; D000818:Animals; D005966:Glucuronidase / Q000097:blood / Q000502:physiology*; D013006:Growth Hormone / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006706:Homeostasis; D006728:Hormones / Q000502:physiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000172:deficiency / Q000502:physiology*; D000090265:Klotho Proteins; D010902:Pituitary Gland / Q000502:physiology
chemical_list: D006728:Hormones; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: Acromegaly; Anorexia; Growth hormone; Growth hormone deficiency; Insulin; Insulin-like growth factor 1; Klotho; Pituitary