The role of estrogen and androgen receptors in bone health and disease

Abstract

Mouse models with cell-specific deletion of the estrogen receptor (ER) α, the androgen receptor (AR) or the receptor activator of nuclear factor κB ligand (RANKL), as well as cascade-selective estrogenic compounds have provided novel insights into the function and signalling of ERα and AR. The studies reveal that the effects of estrogens on trabecular versus cortical bone mass are mediated by direct effects on osteoclasts and osteoblasts, respectively. The protection of cortical bone mass by estrogens is mediated via ERα, using a non-nucleus-initiated mechanism. By contrast, the AR of mature osteoblasts is indispensable for the maintenance of trabecular bone mass in male mammals, but not required for the anabolic effects of androgens on cortical bone. Most unexpectedly, and independently of estrogens, ERα in osteoblast progenitors stimulates Wnt signalling and periosteal bone accrual in response to mechanical strain. RANKL expression in B lymphocytes, but not T lymphocytes, contributes to the loss of trabecular bone caused by estrogen deficiency. In this Review, we summarize this evidence and discuss its implications for understanding the regulation of trabecular and cortical bone mass; the integration of hormonal and mechanical signals; the relative importance of estrogens versus androgens in the male skeleton; and, finally, the pathogenesis and treatment of osteoporosis.

Bu-Shen-Ning-Xin decoction suppresses osteoclastogenesis <i>via </i>increasing dehydroepiandrosterone to prevent postmenopausal osteoporosis

“…Although no specific intra-nuclear receptors of DHEA have been identified to date (14), studies have found that both ERs (15) and androgen receptors (ARs) (15) are involved in mediating the Figure 1. Administration of BSNXD increased serum levels of DHEA and DHEAS but not E2.…”

Variants in RBP4 and AR genes modulate age at onset in familial amyloid polyneuropathy (FAP ATTRV30M)

“…14 The AR gene is located in the X chromosome and its nuclear transcription factor is activated to mediate binding of the androgenic hormones testosterone and 5α-dihydrotestosterone, whereas the HSD17B1 gene may play an important role in regulating the local cellular levels of estradiol. 15 Therefore, the aim of this study was to investigate whether variants of these candidate genes have a modifier effect in AO within FAP ATTRV30M families, what was not taken into account in previous studies.…”

RANKL (Receptor Activator of NFκB Ligand) Produced by Osteocytes Is Required for the Increase in B Cells and Bone Loss Caused by Estrogen Deficiency in Mice

“…Estrogen deficiency in mice increases osteoclast number on cancellous and cortical bone and causes bone loss in both compartments (9). Estrogen deficiency also causes a striking increase in B lymphocyte number in the bone marrow (10,11).…”