5-Androstene-3β,7β,17β-triol (β-AET) Slows Thermal Injury Induced Osteopenia in Mice: Relation to Aging and Osteoporosis

Abstract

5-androstene-3β,7β,17β-triol (β-AET), an active metabolite of dehydroepiandrosterone (DHEA), reversed glucocorticoid (GC)-induced suppression of IL-6, IL-8 and osteoprotegerin production by human osteoblast-like MG-63 cells and promoted osteoblast differentiation of human mesenchymal stem cells (MSCs). In a murine thermal injury model that includes glucocorticoid-induced osteopenia, β-AET significantly (p<0.05) preserved bone mineral content, restored whole body bone mineral content and endochondral growth, suggesting reversal of GC-mediated decreases in chondrocyte proliferation, maturation and osteogenesis in the growth plate. In men and women, levels of β-AET decline with age, consistent with a role for β-AET relevant to diseases associated with aging. β-AET, related compounds or synthetic derivatives may be part of effective therapeutic strategies to accelerate tissue regeneration and prevent or treat diseases associated with aging such as osteoporosis.

The effect of pulsed electromagnetic fields and dehydroepiandrosterone on viability and osteo-induction of human mesenchymal stem cells

“…The results suggest that DHEA significantly decreased viability and increased osteo‐induction of MSCs. Previous research has also shown that androstenetriol, an active metabolite of DHEA, promoted osteoblast differentiation of MSCs (Malik et al ., ). The promoted osteogenesis was particularly clear with osteo‐induced MSCs.…”

Pharmacology and immune modulating properties of 5-androstene-3β,7β,17β-triol, a DHEA metabolite in the human metabolome

“…␤AET is one of several DHEA metabolites with anti-inflammatory activity [29,45], noting that some of these metabolites are also susceptible to metabolism, and therefore may be further transformed in vivo into the active entities. Recent studies suggest natural roles for ␤AET in preserving bone mineral content [46] and preventing the development of metabolic syndrome [35]. In a placebo controlled clinical trial it was shown to lower cholesterol in normal human subjects [47] consistent with DHEA activity in dogs reported by MacEwen and Kurzman [48].…”

“…Accordingly findings with this pharmaceutical may define the roles of ␤AET, a natural component of the human metabolome. In addition to a role in stem cell fate decisions [71], it is involved in metabolic processes, and possesses immune modulation properties that were previously shown to temper autoimmune disease in murine models and shown here to inhibit the acute inflammatory response and resolve immune senescence in aged mice. However, ␤AET's metabolic lability and limited bioavailability preclude its use as a practical treatment for acute inflammation, whereas the pharmacology of 17␣-alkynyl-␤AET is suitable for with this application.…”

The Origin of 7α-Hydroxy-Dehydroepiandrosterone and Its Physiological Role: a History of Discoveries

“…Another related steroid, 5-androstene-3β,7β,17βtriol, exhibits glucocorticoid-opposing and immunemodulating activity (Ahlem et al 2011), and because its plasma levels positively correlate with BMI in healthy men and women, the authors suggested its compensatory role in preventing the development of metabolic syndrome (Auci et al 2011). 5-androstene-3β,7β,17βtriol (β-AET), an active metabolite of dehydroepiandrosterone (DHEA), reversed the glucocorticoid induced suppression of IL-6, IL-8 and osteoprotegerin production (Malik et al 2010). This steroid also influences estrogen receptor beta signaling (Pettersson et al 2010).…”