Estrogenic activity of RU 486 (mifepristone) in rat uterus and cultured uterine myocytes

Article Abstract:

The antiprogestin Ru 486 (mifepristone) may act like an estrogen in uterine myocytes (muscle cells) of the rat. Among other therapeutic applications, RU 486 can terminate pregnancies and is used for treating breast cancer. Researchers analysed the effect of RU 486 on oxytocin receptor concentration, a marker of estrogenic activity. Rats who had their ovaries removed received either a control solution, mifepristone, estrogen, another anti-estrogen or a combination of mifespristone and the other antiestrogen for three days. Analysis of the dissected rat uteri yielded higher oxytocin receptor concentrations following estrogen and Ru 486 therapy only, indicating the presence of higher estrogen levels. Direct manipulation of a hamster muscle cell line and a reporter gene showed estrogen-like activity is dependent on such estrogen-responsive genes.

Author: Sadovsky, Yoel, Dibbs, Khaled I., Li, Xue-Jun, Koide, Samuel S., Adler, Stuart, Fuchs, Anne-Riitta
Muscle cells, Estrogen, Estrogens, Mifepristone

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Expression of beta-adrenergic receptor kinase subtypes in the pregnant rat myometrium

Article Abstract:

Decreased sensitivity to drugs given to prevent preterm labor may be mediated by beta-adrenergic receptor kinase (beta-ARK). Researchers obtained uteri from pregnant and nonpregnant rats and analyzed messenger ribonucleic acid from them. The muscle layer of the late pregnant uterus contained the highest levels of beta-adrenergic receptor-inactivating protein kinase type 2, as compared to earlier pregnant and nonpregnant uteri. Beta-ARK2 may cause uterine muscle to change in late pregnancy to promote labor contractions. Increases of beta-ARK2 may override labor-inducing drugs, suggesting that different dosages of these drugs should be considered.

Author: Ruzycky, Andre L., DeLoia, Julie A.
Drug resistance, Beta adrenoceptors, Adrenergic beta receptors

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Rat uterine myometrium contains the gap junction protein connexin45, which has a differing temporal expression pattern from connexin43

Article Abstract:

Changes in gap junction proteins may play a role in initiating labor. Gap junctions are special connections between uterine muscle cells that allow the uterus to contract in coordinated fashion. Analysis of cultured hamster and human uterine muscle cells and uterine muscle from pregnant rats revealed RNA for making two varieties of gap junction protein, connexin45 and connexin43, as well as the proteins themselves. However, the amount of connexin43 RNA rose markedly at the end of pregnancy in rats whereas connexin45 RNA fell at the end of pregnancy and more than doubled after birth.

Author: Sadovsky, Yoel, Albrecht, Jan L., Atal, Namita S., Tadros, Peter N., Orsino, Angela, Lye, Steven J., Beyer, Eric C.
Cell junctions

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Subjects list: Physiological aspects, Myometrium
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