Zaidi Mone, Iqbal Jameel, Blair Harry C, Zallone Alberta, Davies Terry, Sun Li
Mount Sinai Bone Program, Mount Sinai School of Medicine, New York, NY, USA.
Mt Sinai J Med. 2009 Oct;76(5):474-83. doi: 10.1002/msj.20136.
Bone loss is an inevitable result of getting older in both sexes. This loss is accelerated in women in the early years following menopause and in both sexes with drugs and diseases, prominently hyperthyroidism. Postmenopausal osteoporosis and hyperthyroid osteoporosis, both of which are widely recognized clinical entities, have been thought to arise from low estrogen levels and high thyroid hormone levels, respectively. However, when estrogen declines, follicle-stimulating hormone, an anterior pituitary hormone, rises. Likewise, when thyroid hormone levels rise in hyperthyroidism, thyroid-stimulating hormone levels fall. We have used a complement of mouse genetic, pharmacological, and cell biological approaches to unravel a direct action of follicle-stimulating hormone and thyroid-stimulating hormone on bone remodeling and bone mass. Apart from establishing a novel pituitary-bone axis of physiological significance, our studies challenge the existing 1-hormone, 1-disease paradigm in endocrinology and suggest that a plurality of hormonal disturbances involving pituitary hormones cause postmenopausal and hyperthyroid osteoporoses. New therapeutic targets thus emerge from these studies. Mt Sinai J Med 76:474-483, 2009. (c) 2009 Mount Sinai School of Medicine.
骨质流失是男女衰老过程中不可避免的结果。在绝经后的最初几年，女性的骨质流失会加速，而在男女两性中，药物和疾病（尤其是甲状腺功能亢进）也会加速骨质流失。绝经后骨质疏松症和甲状腺功能亢进性骨质疏松症都是广为人知的临床病症，人们认为它们分别是由雌激素水平低和甲状腺激素水平高引起的。然而，雌激素下降时，垂体前叶激素促卵泡激素会上升。同样，甲状腺功能亢进时甲状腺激素水平升高，促甲状腺激素水平则会下降。我们运用了一系列小鼠遗传学、药理学和细胞生物学方法，来揭示促卵泡激素和促甲状腺激素对骨重塑和骨量的直接作用。除了确立一条具有生理意义的新型垂体 - 骨轴之外，我们的研究还对内分泌学中现有的“一种激素，一种疾病”范式提出了挑战，并表明涉及垂体激素的多种激素紊乱会导致绝经后骨质疏松症和甲状腺功能亢进性骨质疏松症。这些研究因此产生了新的治疗靶点。《西奈山医学杂志》76:474 - 483，2009年。(c) 2009年西奈山医学院。
