INHIBITION OF PROGESTERONE-INDUCED DEVELOPMENT OF GIANT MITOCHONDRIA IN UTERINE GLANDULAR EPITHELIAL-CELLS BY AN ANTIESTROGEN IN RAT

Effect of the antiestrogen ormeloxifene on progesterone-induced develo pment of giant mitochondria in uterine glandular epithelial cells in o variectomized adult Sprague-Dawley rats was investigated. Antiestrogen tamoxifen and antiprogestin onapristone were used for comparison. Wel l-formed giant mitochondria were observed in uterine glandular epithel ial cells in rats treated with progesterone (20 mg/kg, subcutaneous [S C]) per se for three consecutive days. In rats primed with estradiol-1 7 beta (0.5 mu g/day, sc) on days -2 and -1 before progesterone treatm ent, there was, in addition, a marked increase and distension of smoot h endoplasmic reticulum (SER) and Golgi complex, in comparison to exte nsive rough endoplasmic reticulum (RER) and polyribosomes in progester one per se treated rats. Cytological picture in rats receiving single (1.25 mg/kg, day 1, po) or multiple (0.25 mg/kg, days 1-3, po) anti-im plantation doses of ormeloxifene showed marked reduction in glandular epithelial cell height, luminal surface microvilli, RER, polyribosomes and cytoplasm:nucleus ratio, straightening of intercellular membranes , and interdigitation of basement membrane. Mitochondria were of norma l size and nuclei were heterochromatic. Inhibition in the case of tamo xifen (0.1 mg/kg, days 1-3, po) appeared partial and rare giant mitoch ondria with degenerating cristae and outer membranes were apparent. On apristone (10 mg/kg, day 1, sc), in addition to inhibiting development of giant mitochondria, caused extensive vacuolization and distension of intercellular membranes in glandular epithelial cells. (C) 1996 Els evier Science Inc.