Testosterone and DHEA actions in the bone-vascular axis

ADRIÁN CAMPELO; MARÍA MAGDALENA MONTT; SABRINA CEPEDA; GRACIELA SANTILLÁN; TOMMASO SIMONCINI; VIRGINIA MASSHEIMER

Buenos Aires

Congreso; XXXI Annual Meeting of the Argentine Association of Osteology and Mineral Metabolism.; 2014

Asociación Argentina de Osteología y Metabolismo Mineral

Replacement therapy with androgens is proposed for treatment of testosterone (T) deficiency in men and women. We studied the effects of T and DHEA on events mediating bone vascularization such as VEGF, PAI-1 production and endothelial cells (EC) proliferation and migration, and the androgen action on bone cells was also evaluated. Employing wound healing assays we demonstrated that in human umbilical vein EC (HUVEC), both androgens have a stimulatory effect of migration (2 ± 2, 16 ± 4, 90 ± 15 Cont, 1 nM T, 20 nM DHEA EC/field p < 0.01). This effect was confirmed by actin immunocytochemistry (Texas Red Phalloidin) showing both androgens a stimulatory effect on actin cytoskeleton rearrangement. 24 h of treatment with both steroids stimulated cell proliferation (MTT assay) (32 and 12%/Cont 1 nM T and 20 nM DHEA p < 0.05). PAI-1 expression (Western blot) was enhanced by T (0.1, 1 and 10 nM) at all times of treatment (12, 24, 36 and 48 h), with a stimulus of 70 ± 10%/Cont (p < 0.05). No significant effect on PAI-1 was observed when EC were treated with DHEA. VEGF mRNA expression (RTPCR) was enhanced by T at 4 h of treatment (120%/C) and returned to basal levels after 24 h of treatment. T also stimulated the release of VEGF into the medium (19.6 ± 2.2 vs. 22.2 ± 2 Cont vs. T pg/mg prot). DHEA treatment produced no significant change compared with the control. In the mouse osteoblastic cell line MC3T3-E1, treatment with T (1 nM) stimulated FAL activity (33%/Cont p < 0.05), while DHEA significantly inhibited FAL activity and also decreased extracellular Ca2 + content. These results suggest that, concerning the vascular and skeletal actions assayed, T and DHEA effects are not equivalent, T being the androgen that exhibits more favorable effects.