Koike Megumi, Sato Tetsuhiko, Shiozaki Yuji, Komiya Aoi, Miura Mizuki, Higashi Ayami, Ishikawa Akane, Takayanagi Kaori, Uga Minori, Miyamoto Ken-Ichi, Segawa Hiroko
Department of Applied Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
General Medicine, Nagoya Daini Red Cross Hospital, 2-9 Myoken-cho, Showa-ku, Nagoya 466-8650, Japan.
J Clin Biochem Nutr. 2024 May;74(3):221-229. doi: 10.3164/jcbn.23-127. Epub 2024 Jan 16.
Growth hormone (GH) exerts multiple effects on different organs directly or via its main mediator, insulin-like growth factor1 (IGF1). In this study, we focused on the novel relationship between GH action and the antiaging hormone α-klotho. Immunofluorescent staining of α-klotho was observed in the renal distal tubules and pituitary glands of somatostatin- and GH-positive cells in wild-type (WT) mice. Treatment of 4-week-old WT mice with GH increased IGF1 mRNA expression in the pituitary gland, liver, heart, kidney, and bone but increased α-klotho mRNA expression only in the pituitary gland, kidney, and bone. Increased α-klotho protein levels were observed in the kidney but not in the pituitary gland. No induction of α-klotho RNA expression by GH was observed in juvenile mice with kidney disease, indicating GH resistance. Furthermore, GH and α-klotho supplementation in HEK293 cells transfected with GHR increased Janus kinase 2 mRNA (a GH downstream signal) expression compared to supplementation with GH alone. In conclusion, we suggest that 1) the kidney is the main source of secreted α-klotho, which is detected in blood by the downstream action of GH, 2) α-klotho induction by GH is resistant in kidney disease, and 3) α-klotho might be an enhanced regulator of GH signaling.
生长激素（GH）直接或通过其主要介质胰岛素样生长因子1（IGF1）对不同器官发挥多种作用。在本研究中，我们重点关注了GH作用与抗衰老激素α-klotho之间的新关系。在野生型（WT）小鼠的肾远端小管以及生长抑素和GH阳性细胞的垂体中观察到α-klotho的免疫荧光染色。用GH处理4周龄的WT小鼠可增加垂体、肝脏、心脏、肾脏和骨骼中IGF1 mRNA的表达，但仅增加垂体、肾脏和骨骼中α-klotho mRNA的表达。在肾脏中观察到α-klotho蛋白水平升高，但在垂体中未观察到。在患有肾病的幼年小鼠中未观察到GH对α-klotho RNA表达的诱导作用，表明存在GH抵抗。此外，与单独补充GH相比，在转染了GHR的HEK293细胞中补充GH和α-klotho可增加Janus激酶2 mRNA（一种GH下游信号）的表达。总之，我们认为：1）肾脏是分泌的α-klotho的主要来源，通过GH的下游作用在血液中被检测到；2）GH对α-klotho的诱导在肾病中具有抗性；3）α-klotho可能是GH信号的增强调节剂。
