Dehydroepiandrosterone and Bone

In humans, dehydroepiandrosterone (DHEA), secreted mainly from the adrenal cortex, and its sulfate ester, DHEAS, are the most abundant circulating steroids. DHEA/DHEAS possess pleiotropic effects in human aging, bone, metabolic diseases, neurologic function/neurodegenerative diseases, cancer, immune system and disorders, cardiovascular diseases, diabetes, muscle function, sexual dysfunction, and other health conditions. The age-related reduced levels of DHEA and DHEAS are associated with bone mineral density measures of osteopenia and osteoporosis. Clinical, epidemiological, and experimental studies indicate that DHEA replacement therapy may be beneficial for bone health through its inhibition of skeletal catabolic IL-6 and stimulation of osteoanabolic IGF-I-mediated mechanisms. Studies with primary cultures of human bone marrow-derived mesenchymal stem cells (hMSCs) were used to show that DHEA stimulates osteoblastogenesis. The in vitro stimulation of both osteoblastogenesis and IGF-I gene expression by DHEA in hMSCs requires IGF-I receptor, PI3K, p38 MAPK, or p42/44 MAPK signaling pathways. The in vitro inhibition of IL-6 secretion in hMSCs by DHEA was more consistent and extensive than by estradiol or dihydrotestosterone. In summary, evidence from us and others indicates that DHEA may be useful for treating bone diseases through its inhibition of skeletal catabolic IL-6 and stimulation of anabolic IGF-I-mediated mechanisms.