ESTROGEN REPLACEMENT THERAPY WITH ITS PHYSIOLOGICAL DOSE DOES NOT ELIMINATE THE AGGRAVATING EFFECT OF OVARIECTOMY ON GLOMERULAR INJURY IN HYPERCHOLESTEROLEMIC FEMALE IMAI RATS

Hypercholesterolemic Imai rats spontaneously develop proteinuria and g lomerulosclerosis, especially in males. Estrogen administration attenu ated glomerular injury in male Imai rats, and the aggravating effect o f ovariectomy in female rats is found. To clarify whether this aggrava ting effect of ovariectomy is due to a lack of estrogen, we administer ed estrogen to ovariectomized female Imai rats. At 6 weeks of age, gro up 1 (control) was sham-operated and group 2 was ovariectomized. Group s 3 and 4 were ovariectomized and received estrogen replacement therap y (0.1 mg in group 3 and 0.2 mg in group 4 once a month subcutaneously ). Body weight, urinary protein and serum constituents were investigat ed every month from 3 to 6 months of age. At 6 months of age, rats wer e studied morphologically. Estrogen replacement therapy increased seru m estrogen to levels close to those of controls when 0.1 mg was used, or higher when 0.2 mg was used. Estrogen replacement therapy with 0.1 mg did not eliminate the aggravating effect of ovariectomy on glomerul ar injury and rather aggravated it, but conversely therapy with 0.2 mg attenuated glomerular injury and abolished the aggravating effect of ovariectomy. Estrogen replacement therapy markedly elevated serum GH l evels dose-dependently. These results suggested that other hormones as well as estrogen may play a protective role of the ovary for the deve lopment of glomerular injury, and that estrogen seems to exert a dual effect on glomerular injury.