| Abstract | 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 (E2), 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 E2 (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 E2, with maximum at 20 microg/rat. Age-matched diabetic female rats exhibited a remarkable decreased response to E2 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 E2 but not to Ral in cultured human vascular and bone cells. In summary, diabetes mellitus decreases CK response to E2 but not that of Ral in skeletal and vascular tissues. The decreased response to E2 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. |
| Authors | Dalia Somjen, Michal Shen, Naftali Stern, Nitsa Mirsky
(Affiliation: Institute of Endocrinology, Metabolism and Hypertension, Tel-Aviv Sourasky Medical Center and The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 64239, Israel. dalias at tasmc.health.gov.il)
|
| Journal | Journal of cellular biochemistry
(J Cell Biochem)
Vol. 99
Issue 1
Pg. 133-9
(Sep 1 2006)
ISSN: 0730-2312 United States |
| PMID | 16598752
(Publication Type: Journal Article)
|
| Chemical References |
- Selective Estrogen Receptor Modulators
- Estradiol
- Raloxifene
- Creatine Kinase
|
| Topics |
- Animals
- Bone and Bones
(drug effects, enzymology)
- Cardiovascular System
(drug effects, enzymology)
- Creatine Kinase
(drug effects, metabolism)
- Diabetes Mellitus, Experimental
(drug therapy, enzymology)
- Dose-Response Relationship, Drug
- Estradiol
(pharmacology)
- Female
- Ovariectomy
- Raloxifene
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Selective Estrogen Receptor Modulators
(pharmacology)
- Uterus
(drug effects, enzymology)
|
