ERa and ERb specific effects on movement drive, body weight, and bone density in ovariectomized female rats

Reduced estrogen levels occurring during menopause in women, are accompanied by a variety of disorders, e.g. hot flushes, depressions, osteoporosis, increase in body weight and reduced movement drive. To study ER subtype specific effects on such disorders in an animal model, ovariectomized (OVX) female Wistar rats were either treated with 17-b Estradiol (4µg/KG b.wt/d), the ERa specific agonist (ERA) 16a-LE2.2 (10µg/KG b.wt/d) or the ERb specific agonist (ERB) 8b-VE2 (100µg/KG b.wt/d) for 3 weeks. Vehicle treated OVX animals served as controls. Movement activity, changes of body weight and of trabecular bone mineral density (BMD) in the tibia (determined by quantitative computer tomography) were analyzed and correlated to uterine wet weights. Uterine wet weights were stimulated significantly by E2 substitution, and treatment with ERA but only marginally in ERB treated animals. E2 and ERA treatment, but not ERB, significantly increased the movement activity of OVX rats. During 3 weeks, the increase of body weight observed in animals substituted with ERA was comparable to the effect after treatment with E2, whitch reduced the increase rate. An eminently higher rate was observed in OVX and ERB treated animals. ERA, but not ERB, lowers the increase of body weight intensely compared to OVX animals, which demonstrates the involvement of metabolic changes controlled by activated ERa. The strongest decrease of BMD was detected in OVX and ERB treated rats. Substitution with E2 and ERA resulted in an increased BMD. These observations correlate positively to the measured expression of BMP-2 protein in the tibia. Highest BMP-2 expression was detected in ERA and E2 treated individuals.

In conclusion, our data demonstrate that ERa is one meditor of E2 effects on body weight, movement drive, and bone formation, whereas activation of ERb has obviously no influence on these parameters. In further investigations effects of ERa/ERb heterodimers on these parameters should be observed.