Bones and Hormones: Interaction between Hormones of the Hypothalamus, Pituitary, Adipose Tissue and Bone

Abstract

The bony skeleton, as a structural foundation for the human body, is essential in providing mechanical function and movement. The human skeleton is a highly specialized and dynamic organ that undergoes continuous remodeling as it adapts to the demands of its environment. Advances in research over the last decade have shone light on the various hormones that influence this process, modulating the metabolism and structural integrity of bone. More recently, novel and non-traditional functions of hypothalamic, pituitary, and adipose hormones and their effects on bone homeostasis have been proposed. This review highlights recent work on physiological bone remodeling and discusses our knowledge, as it currently stands, on the systemic interplay of factors regulating this interaction. In this review, we provide a summary of the literature on the relationship between bone physiology and hormones including kisspeptin, neuropeptide Y, follicle-stimulating hormone (FSH), prolactin (PRL), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), growth hormone (GH), leptin, and adiponectin. The discovery and understanding of this new functionality unveils an entirely new layer of physiologic circuitry.

Keywords: bone; fat tissue; hypothalamus; pituitary; pituitary–bone axis.

Figure 1

The multidirectional effect of leptin on bone metabolism. Lepr—leptin receptor; Htr2c—5-hydroxytryptamine receptor 2c; CART—cocaine- and amphetamine-regulated transcript; IGF1—insulin-like growth factor 1. Leptin has a direct anabolic effect on bone metabolism, however, it also modulates bone physiology indirectly by acting on the hypothalamus, acting on the sympathetic nervous system and by affecting the endocrine system. The direct action of leptin on the bone consists of osteoblast differentiation, and the enhanced synthesis of type I collagen and osteoprotegerin, thus increasing bone mineralization and inhibiting osteoclast activity and bone resorption. The effect of hormones on bone tissue is also relatively well known. It is known that leptin, by acting in the brainstem, regulates the function of the endocrine glands by affecting the pituitary gland and hormones produced by the ovary, parathyroid gland or adrenal cortex, which regulate bone metabolism. Still the most controversial is the role of leptin in the hypothalamus and the process of bone formation. The balance of the central and peripheral effects of leptin on bone metabolism remains unspecified, although recent studies have demonstrated that leptin’s direct effects on bone cells may override its actions via the central nervous system.