DIFFERENT EFFECT OF ESTROGEN ADMINISTRATION FROM CASTRATION ON GLOMERULAR INJURY IN UNILATERALLY NEPHRECTOMIZED MALE SPRAGUE-DAWLEY RATS

We have already reported an equally attenuating effect of castration o r estrogen administration on the development of focal segmental glomer ulosclerosis (FSGS) in the animal models of a short-term experimental period ended at 24 weeks. In the present study, to clarify the importa nce of the experimental period in studying the pathogenesis of the dev elopment of FSGS, we investigated a long-term effect of castration or estrogen administration on FSGS using an experimental model of unineph rectomized Sprague-Dawley (SD) rats ended at 54 weeks. Thirty male SD rats received unilaterally right nephrectomy at 6 weeks of age. They w ere divided into three groups: group 1 was control, group 2 was castra ted at 6 weeks, and group 3 was administered 0.2 mg estrogen subcutane ously once a month from 6 weeks of age. Body weight, urinary protein, serum albumin and other serum constituents were investigated every 12 weeks from 18 to 54 weeks of age. Each group was studied morphological ly at the end of the experiment. Castration attenuated glomerular inju ry to the same extent as seen in the study of a short-term experimenta l period, while estrogen administration failed to attenuate glomerular injury, although each treatment equally suppressed an urinary excreti on of a sex-related low-molecular-weight (LMW) protein. Castration red uced significantly kidney weight (KW), glomerular volume (GV) and seru m growth hormone (GH) levels, but estrogen treatment failed to reduce KW and GV, and conversely elevated GH levels. These results suggest th at a sex-related LMW protein influenced by castration or estrogen trea tment may not play an important role in the development of FSGS and th at an increase in plasma GH levels may contribute to the failure of an attenuating effect of estrogen on glomerular injury.