Extragonadal Effects of Follicle-Stimulating Hormone on Osteoporosis and Cardiovascular Disease in Women during Menopausal Transition. (August 2018)

• Record Type: Journal Article
• Authors: Zhu, Dongxing; Li, Xiaosa; Macrae, Vicky E.; Simoncini, Tommaso; Fu, Xiaodong
• Is Part Of: Trends in endocrinology and metabolism. Volume 29:Number 8(2018)
• Page Start: 571
• Page End: 580
• Publication Date: 2018-08
• Subjects: Follicle-stimulating hormone -- postmenopause -- osteoporosis -- cardiovascular disease -- extragonadal effects; Endocrinology -- Periodicals; Metabolism -- Periodicals; Metabolism; 616.4
• DOI: 10.1016/j.tem.2018.06.001
• Languages: English
• ISSNs: 1043-2760

Abstract

Abstract : The risk of osteoporosis and cardiovascular disease increases significantly in postmenopausal women. Until recently, the underlying mechanisms have been primarily attributed to estrogen decline following menopause. However, follicle-stimulating hormone (FSH) levels rise sharply during menopausal transition and are maintained at elevated levels for many years. FSH receptor has been detected in various extragonadal sites, including osteoclasts and endothelial cells. Recent advances suggest FSH may contribute to postmenopausal osteoporosis and cardiovascular disease. Here, we review the key actions through which FSH contributes to the risk of osteoporosis and cardiovascular disease in women as they transition through menopause. Advancing our understanding of the precise mechanisms through which FSH promotes osteoporosis and cardiovascular disease may provide new opportunities for improving health-span for postmenopausal women. Highlights: Epidemiological studies have demonstrated that FSH levels are positively associated with postmenopausal osteoporosis and cardiovascular disease. Besides gonadal tissues, FSHR is found to be expressed by a range of extragonadal sites, including osteoclasts and endothelial cells. FSH treatment stimulates the formation, function, and survival of osteoclast cells, the cells that are responsible for bone resorption. In addition, FSH administration significantly promotes atherosclerosis in ovariectomized ApoE –/– mice by upregulating VCAM-1 expression in human umbilical vein endothelial cells and subsequently increasing human monocyte adhesion. Blockade of FSH with a specific antibody targeting its β subunit enhances bone mass and reduces body fat and atherosclerosis in mouse models. FSH represents a potential novel therapeutic target for the treatment of postmenopausal osteoporosis and cardiovascular disease.