Abstract
Androgens are not only essential for bone development but for the maintenance of bone mass. Therefore, conditions with androgen deficiency, such as male hypogonadism, androgen-insensitive syndromes, and prostate cancer with androgen deprivation therapy are strongly associated with bone loss and increased fracture risk. Here we summarize the skeletal effects of androgens—androgen receptors (AR) actions based on in vitro and in vivo studies from animals and humans, and discuss bone loss due to androgens/AR deficiency to clarify the molecular basis for the anabolic action of androgens and AR in bone homeostasis and unravel the functions of androgen/AR signaling in healthy and disease states. Moreover, we provide evidence for the skeletal benefits of androgen therapy and elucidate why androgens are more beneficial than male sexual hormones, highlighting their therapeutic potential as osteoanabolic steroids in improving bone fracture repair. Finally, the application of selective androgen receptor modulators may provide new approaches for the treatment of osteoporosis and fractures as well as building stronger bones in diseases dependent on androgens/AR status.
Highlights
The discovery of androgen actions initiated in the 19th century with the idea of self-injection with testicular extracts from pigs or dogs to restore vitality by Dr Charles Brown–Séquard [1].It was known that the development and maintenance of male characteristics are modulated through androgen receptors (AR) [2], designated as NR3C4
There has been a lot of progress in our understanding of estrogen effects on bone, which already led to improved osteoporosis treatment
Additional questions are raised through recent discoveries in the field of bone biology and physiology
Summary
The discovery of androgen actions initiated in the 19th century with the idea of self-injection with testicular extracts from pigs or dogs to restore vitality by Dr Charles Brown–Séquard [1]. Cells 2019, 8, 1318 through signal transduction via (a) binding to AR, and (b) conversion to 17-beta estradiol (E2) via the enzyme aromatase (from cytochrome P450 family) which binds to estrogen receptors (ERs) [3,4]. Both circulating and peripheral effects of testosterone on the body depend on its conversion to DHT by the local enzyme 5α-reductase (SRD5A; type I and II) in target tissues. The activation of AR and ERα, but not ERβ, is associated with maintenance of the trabecular bone. (IGF-1) in serum [5]
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