INVESTIGADORES
PELLEGRINI Gretel Gisela
congresos y reuniones científicas
Título:
Distinct mechanisms regulate the response of female and male skeletons to sex steroid deficiency and to the bone protective effects of berry-enriched diets.
Autor/es:
SATO AY; PELLEGRINI GG; CREGOR, M; MCANDREWS K; ATKINSON E; RODRIGUEZ MM; CHOI R; PLOTKIN L; MCCABE LD; MCCABE GP; WEAVER C; BURR D; BELLIDO T
Reunión:
Congreso; American Society for Bone and Mineral Research Annual Meeting; 2018
Institución organizadora:
ASBMR
Resumen:
There is an unmet need for interventions that prevent bone loss induced by sex steroid deficiency with better compliance, lower side effects, and tailored to patients of either sex. Sex steroid deficiency is accompanied by accumulation of reactive oxygen species (ROS) in bone. ROS, in turn, activates the transcription factor Nrf2 and increases the endogenous antioxidant response (EAR), in an attempt to mitigate the damaging oxidative effects. We investigated herein the ability of diets containing blueberries enriched in anti-oxidant metabolites to prevent sex steroid deficiency in 4 month-old WT and Nrf2 KO littermate mice (N=19-26). In mice fed a control diet, ovariectomy (OVX) or orchidectomy (ORX) induced the expected bone loss after 6 or 4 weeks, respectively. Similar bone loss in female or male mice was exhibited by WT and KO mice, as quantified by % change BMD/month or final BMD. From 3 different diets containg 10% dry berries, only the diet with Montgomery berries decreased the rate of bone loss, either fully in female or partially in male mice. However, whereas the berry diet prevented bone loss in both WT and KO female mice, it only prevented bone loss in WT male mice. OVX decreased the expression of the estrogen response element (RE)-containing gene C3 and ORX decreased the expression of the androgen RE-containing gene Rhox5 in bone, in both WT and KO mice fed control diet. The expression of C3 with OVX or Rhox5 with ORX remained low in mice fed the berry diet, demonstrating that bone protection is not due to estrogenic or androgenic actions of the diet. Further, OVX increased the EAR in bone, but ORX did not. Moreover, the berry diet prevented the increase in EAR induced by estrogen deficiency but it did not alter EAR in androgen deficiency. And, prevention of OVX-induced EAR by the berry diet was dependent on Nrf2 as was observed in WT but not in KO mice. In summary, (1) bone loss induced by either estrogen or androgen deficiency is not altered by Nrf2 expression; (2) berry diet-induced skeletal protection depends on sex and is exerted by a mechanism independent of canonical ERE or ARE signaling; and (3) the EAR in bone with sex steroid deficiency or in response to the berry diet also depends on sex. Therefore, distinct mechanisms underly the response of female and male skeletons to sex steroid deficiency and to the bone protective effects of berry diets, suggesting that optimal results might be reached with sex-tailored interventions.