Role of the pituitary-bone axis in skeletal pathophysiology

Abstract

Embedded within textbooks for decades is the hard fact that releasing hormones from the anterior pituitary, namely, follicle-stimulating hormone, thyroid-stimulating hormone and adrenocorticotropic hormone, stimulate master hormone secretion from target endocrine organs. We propose a paradigm shift in endocrine physiology, which is that these hormones act by design on bone directly, also now considered an endocrine organ. Complementary investigations using mouse genetic and cell biological approaches reveal that follicle-stimulating hormone and thyroid-stimulating hormone act on bone cells directly to regulate bone remodeling and bone mass. Thyroid-stimulating hormone inhibits bone remodeling, whereas follicle-stimulating hormone stimulates it. We also find that the posterior pituitary hormone oxytocin is anabolic to the skeleton. An ambitious extrapolation is that a plurality of pituitary hormones acts in concert as part of a 'pituitary-bone' axis to regulate skeletal integrity in health and disease. When dysregulated master hormone levels during hypogonadism and hyperthyroidism cause altered pituitary hormone secretion through hypothalamic feedback, the latter hormones contribute to the skeletal loss.