Effects of sex steroids on bones and muscles: Similarities, parallels, and putative interactions in health and disease

Abstract

Estrogens and androgens influence the growth and maintenance of bones and muscles and are responsible for their sexual dimorphism. A decline in their circulating levels leads to loss of mass and functional integrity in both tissues. In the article, we highlight the similarities of the molecular and cellular mechanisms of action of sex steroids in the two tissues; the commonality of a critical role of mechanical forces on tissue mass and function; emerging evidence for an interplay between mechanical forces and hormonal and growth factor signals in both bones and muscles; as well as the current state of evidence for or against a cross-talk between muscles and bone. In addition, we review evidence for the parallels in the development of osteoporosis and sarcopenia with advancing age and the potential common mechanisms responsible for the age-dependent involution of these two tissues. Lastly, we discuss the striking difference in the availability of several drug therapies for the prevention and treatment of osteoporosis, as compared to none for sarcopenia. This article is part of a Special Issue entitled "Muscle Bone Interactions".

Keywords: Androgens; Bone cells; Estrogens; Muscle fibers; Osteoporosis; Sarcopenia.

Figure 1

Molecular mechanisms of action of ERα. a) Classic genomic signalling, in which ligand-activated ERα dimers attach to EREs on DNA and activate or repress transcription. b) ERE-independent genomic signalling, in which ligandactivated ERα binds to other transcription factors (such as the p50 and p65 subunits of NF-κB), which prevent them from binding to their response elements. c,d) Nongenotropic mode of action, in which ligand-activated ERα (in the plasma membrane) activates cytoplasmic kinases which, in turn, induce the phosphorylation of substrate proteins and transcription factors (such as Elk-1 and AP-1) that (c) positively or (d) negatively regulate transcription. Abbreviations: AP-1, transcription factor AP-1; CoA, coenzyme A; Elk-1, ETS domain-containing protein Elk-1; ERα, estrogen receptor α; ERE, estrogen response element; Shc, Shc-transforming protein; SRE, serum response element. Reproduced from: Stavros C. Manolagas, Charles A. O'Brien, and Maria Almeida. Nature Reviews Endocrinology. 2013, 9: 699–712.

Figure 2. Similarities of the effects of sex steroids in bones and muscles