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| Unit 8: Demos |
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Insulin
structure (9b) Thyroid hormones (12b) Other hormones involved in regulation of blood sugar (15b) Adrenal cortex negative feedback (16e) Estrogen receptor (optional) External versus internal fertilization |
RU 486 AND ITS ACTION What has come to be known as the “French abortion pill,” RU 486, is a steroid that has a high affinity for the progesterone receptor. It is the first available “antiprogesterone” and has been used successfully as a medical alternative for voluntary early pregnancy interruption. It is also effective in treating endometriosis, uterine fibroids, beat cancer, and other hormone related conditions. Recent research has provided some insight into the cellular and molecular mechanism of action of both RU 486 and progesterone. Progesterone is essential for maintenance of the uterine lining during implantation and pregnancy. RU 486, like progesterone and other steroids (Fig. 1), is lipid soluble and thus able to penetrate the plasma membrane and enter the cytoplasm of the target cell. Once inside the cell, both progesterone and RU 486 interact with specific progesterone-receptor proteins in the nucleus. The complex consists of two parts, one protein which has a binding site for progesterone, and a second protein, called heat shock protein (hsp) (Fig. 2). Both RU 486 and progesterone compete for the same binding site on the progesterone-receptor, but RU 486 actually has a higher affinity for the receptor than progesterone. When progesterone is bound to the receptor, the progesterone-receptor complex is able to recognize and find to a specific site on DNA in the nucleus, thereby initiating transcription of specific genes (Fig. 2A) that code for proteins necessary for the pregnancy to continue. When RU 486 is bound instead of progesterone, the receptor-RU 486 complex does not trigger the normal response. It is thought that hsp may not separate so the RU 486-receptor complex cannot interact properly with the DNA (Fig. 2C) or, if it does, the complex may be altered in some way as to interfere with the transcription process (Fig. 2B). RU 486 is an antiprogesterone, since it occupies the binding site of the receptor without triggering a cellular response.
RU 486 INTERRUPTS PREGNANCY It was hypothesized that a short interruption in the supply of progesterone to the pregnant human uterus would cause irreversible damage to the lining, leading to a sloughing off of the uterine lining and termination of the pregnancy. Clinical trials and experience for several years in different countries have confirmed this hypothesis. In addition, the administration of RU 486 has been found to produce an increase in the secretion of prostaglandins, hormone-like substances that are produced by a variety of animal tissues, including the uterine lining. Prostaglandins in the uterus promote dilation and softening of the cervix. The “abortion pill” is a medication that ends an early pregnancy (up to 63 days). It is now called mifepristone (it was called RU-486 when it was being developed). The FDA approved the use of this medication in the U.S. in 2000. The original treatment was RU-486 followed by an injection of prostaglandins, but the new “pill only treatment” consists of mifepristone followed by a second pill, misoprostol, a synthetic prostaglandin analog. The combination is 97 percent effective in ending pregnancy. Most women can have a medication abortion safely, but, as with any medical procedure, there are risks. The risks are rare but may include incomplete abortion, infection, and heavy bleeding. Many women choose a medication abortion because it can be done very early, and is private – the abortion will occur at home, and for most is similar to having a miscarriage.
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