The bleeding corpus luteum. Analysis of 40 confirmed cases.
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Recent studies from this laboratory have shown that the large luteal cell of the pregnant rat contains an abundant 32 kilodalton (32K) phosphoprotein which is up-regulated by estradiol. In order to assess the potential importance of this protein and to more fully understand its function, a specific polyclonal antibody was produced against the 32K and was used to examine its intraovarian localization, its tissue specificity, and its developmental regulation. Immunocytochemical localization of the 32K in the ovary of the pregnant rat found this protein to be selectively and abundantly expressed in the corpus luteum. Immunofluorescence study of small and large luteal cell populations clearly revealed an extensive localization of the 32K in the large luteal cells. Western blot analysis revealed that the 32K was absent from all steroidogenic and nonsteroidogenic tissues. Whereas this protein was absent from all other tissues examined in the rat, it was clearly expressed in corpora lutea of different animal species, including the mouse, hamster, cow, human, and pig. Although undetectable by immunohistochemistry, Western blot analysis showed this protein to be present in the follicle but at levels markedly lower than in the corpus luteum. Analysis of theca and granulosa cells revealed the presence of the 32K in both cell types. To further examine the developmental expression of this protein throughout gestation, Western blot analysis of microsomal fractions isolated from rat corpora lutea on days 3-21 of pregnancy was performed. The 32K was detected at low levels in early pregnancy, increased markedly on day 11, reached a peak on days 14-15, and remained elevated through day 21. Treatment with estradiol and PRL increased the content of the 32K in the corpus luteum. Human CG, known to cause follicular development to the preovulatory stage and to enhance luteal estradiol synthesis, also increased levels of the 32K in the corpus luteum, while it concomitantly decreased this protein in the follicle. In summary, the presence of a unique ovarian-specific 32 kilodalton protein has been established. This protein, which is present in low abundance in theca and granulosa cells, is localized to the large luteal cell and becomes abundantly expressed during midpregnancy, a time when there is a remarkable increase in luteal cell size and activity. Results of this study also demonstrate a multihormonal regulation of the 32K by tropic hormones. Thus, because of its apparent uniqueness and its timely and highly regionalized expression, the 32K may play a central role in the regulation of corpus luteum growth and function.
UNLABELLED: The antiprogesterone steroid RU 486 (17 beta-hydroxy-11 beta-4-dimethyl-aminophenyl)17 alpha(1-propynyl)estra-4,9-dien-3-one) was given orally to 32 normally cycling women for 4 days, starting on the fourth day of the luteal phase. Uterine bleeding occurred on the third day of RU 486 administration in all 14 women treated with 100 mg/day, in 7 of the 8 women treated with 50 mg, and in 8 of 10 women receiving 25 mg/day. Premature luteal regression induced by RU 486 occurred in 8 women treated with 100 mg/day, in 3 treated with 50 mg, and in 2 receiving 25 mg/day. Plasma LH was measured every 15 min from 0800-1200 h for 5 days in 17 women. Mean LH levels decreased and pulsatile release disappeared in 7 of the 8 women treated with 100 mg, in 2 of 4 receiving 50 mg, and in 1 of 5 treated with 25 mg. RU 486 had no effect when given to 5 women with anovulatory cycles for 4 days starting on day 18 of the cycle. IN CONCLUSION: 1) RU 486, given to normally cycling women at midluteal phase, provokes uterine bleeding. 2) This effect occurs whether or not luteal regression is induced by the compound, indicating that RU 486 acts directly upon the endometrial tissue, very likely at the progesterone receptor level. 3) The drug may impair simultaneously or separately luteal function and gonadotropin secretion in a dose-dependent manner. 4) The lack of antiglucocorticosteroid activity, at the dosage of 100 mg/day, suggests that RU 486 may be useful for fertility control.
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