| Diabetes mellitus increases the risk for CVD in women. While there
is considerable evidence suggesting beneficial effects of estrogen
on decreasing lipid peroxidation, atherosclerotic processes, and cardiovascular
diseases, diabetes negates most estrogen protective effects as well
as the skeletal protective effects of estrogens, which are not discernable
in diabetic women. In the present study, we examined the in vivo effects
of ESTRADIOL-17beta
(E(2)), on creatine kinase (CK)-specific activity, in estrogen-responsive
organs from healthy and diabetic rats. Healthy or diabetic (streptozotocin-induced)
female rats were injected with either E(2) (10-50 microg/rat) or RALOXIFENE (Ral;
500-1,000 microg/rat). Twenty-four hours following the injection, animals
were sacrificed; their organs removed and assayed for CK-specific activity.
CK-specific activity in different organs [Left ventricle of heart (Lv),
uterus (Ut), aorta (Ao), para uterine adipose tissue (Ad), epiphyseal
cartilage (Ep), and diaphyseal bone (Di)] from healthy animals, was
stimulated with increased doses of E(2), with maximum at 20 microg/rat.
Age-matched diabetic female rats exhibited a remarkable decreased response
to E(2) in all organs except Ut. In contrast, the response to Ral was
not altered in diabetic rats. Similar results were observed in organs
from ovariectomized female rats (Ovx), healthy or diabetic. These results
support our previous in vitro findings, demonstrating that hyperglycemia
decreases CK response to E(2) but not to Ral in cultured human vascular
and bone cells. In summary, diabetes mellitus decreases CK response
to E(2) but not that of Ral in skeletal and vascular tissues. The decreased
response to E(2) detected in organs derived from diabetic rats might
be due to changes in nuclear and/or membrane estrogen receptors and/or
other genomic and non-genomic pathways, as was shown in in vitro cellular
models. |
