Inhibition of progesterone-induced development of giant mitochondria in uterine glandular epithelial cells by an antiestrogen in rat.

Effect of antiestrogen ormeloxifene on progesterone-induced development of giant mitochondria in uterine glandular epithelial cells in ovariectomized adult Sprague-Dawley rats was investigated. Antiestrogen tamoxifen and antiprogestin onapristone were used for comparison. Well-formed giant mitochondria were observed in uterine glandular epithelial cells in rats treated with progesterone (20 mg/kg, subcutaneous [SC] per se for three consecutive days. In rats primed with estradiol-17 beta (0.5 micrograms/day, s.c.) on days-2 and -1 before progesterone treatment, there was, in addition, a marked increase and distension of smooth endoplasmic reticulum (SER) and Golgi complex, in comparison to extensive rough endoplasmic reticulum (RER) and polyribosomes in progesterone per se treated rats. Cytological picture in rats receiving single (1.25 mg/kg, day 1, p.o.) or multiple (0.25 mg/kg, days 1-3, p.o.) anti-implantation 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 normal size and nuclei were heterochromatic. Inhibition in the case of tamoxifen (0.1 mg/kg, days 1-3, p.o.) appeared partial and rare giant mitochondria with degenerating cristae and outer membranes were apparent. Onapristone (10 mg/kg, day 1, s.c.), in addition to inhibiting development of giant mitochondria, caused extensive vacuolization and distension of intercellular membranes in glandular epithelial cells.