Deciphering RU-486

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Biology 202
2001 Third Web Report
On Serendip

Deciphering RU-486

Caroline Ridgway

When told there is a drug available that may prove useful in the treatment of everything from cancer to HIV to Alzheimer's Disease (1), the tendency would be to ask why its use isn't more pervasive. Conversely, when told there is a drug that functions to terminate unwanted pregnancies as well as preventing them from occurring at all (1), it would be more likely to call into question the ethics of such a design. However, when considering a drug that does all these things, the need to see everything as black and white suddenly becomes less easily met. The drug RU-486, simultaneously vilified by anti-abortion advocates and praised by many research scientists, is just such a drug, and it presents a decidedly modern moral dilemma. Its inhibitory effects on the hormone progesterone are fairly effective in ending a pregnancy in its early stages (1), with this aspect of the drug being successfully marketed in Europe (6) prior to its more recent entrance into this country (13). Its other uses have been less widely publicized, largely because to an extent they are just being developed. RU-486 appears to also have an inhibitory effect on the class of stress hormones known as glucocorticoids, which have been recognized as being extremely harmful to the body in a whole host of ways given a high enough concentration. With the high-stress lifestyles we lead today and little evolutionary back-up to deal with that, it is imperative that we come up with a method of treating stress-related illness. It is worth considering at what point the more controversial use of RU-486 should be put aside to allow its beneficial features to achieve their fullest potential.

 

The clinical efficacy of RU-486 comes in its ability to bind to receptors in various locations throughout the body (2), often with better specificity than the molecule actually meant to bind to that particular site. The cause of its contraceptive effect is the drug's proclivity for binding with progesterone receptors, thereby interrupting the chain of DNA transcription that allows for the hormonal cascade necessary for pregnancy to proceed. If implantation of the fertilized egg in the uterus has occurred and the resulting surge of progesterone is not stemmed, pregnancy will generally continue unabated. Introducing a progesterone antagonist such as RU-486 interrupts the development of the uterine lining and, as a result, the pregnancy cannot occur or progress any further and menstruation will follow, returning to a normal cycle. RU-486 has also shown a great affinity for glucocorticoid receptors. Of particular interest are the varying concentrations of glucocorticoid receptors throughout the brain, especially in areas such as the hippocampus that have an exceptionally high metabolic demand and appear to be first to feel any negative impact. The deleterious effects of glucocorticoids are manifested when they become overwhelming in concentration, to the degree that down regulation occurs within the sets of glucocorticoid receptors (3). RU-486, a glucocorticoid antagonist, binds to these receptors and prevents, or at least slows, damage to cell function.

 

However the debate is not so much in how RU-486 works, but in whether it should be allowed to work. Depending on the perspective taken, the drug can be seen as a potential medical panacea or as a means of propagating a social evil ‹ two views that are hard to reconcile. Given that it was introduced into this country as the so-called "abortion drug" it is understandable that the anti-abortion factions would have perceived it as a direct threat. The National Right to Life Committee (NRLC) published an official statement following the FDA's approval of RU-486 (4). This document highlights the dangers of the drug and their fundamental opposition to abortion by any means. Though it is clear in its disapproving message, it maintains a mostly professional tone throughout the text. However, it is a professionalism that is clearly, though not surprisingly, biased. The NRLC¹s resistance to RU-486 is entirely a function of a more basic objection to abortion, and much of their argument against the drug deals with the semantic details that have always been a point of contention when discussing abortion. Other forums are considerably more militant in their objections. More conservative groups try to depict the approval of RU-486 as a product of government conspiracy, with ties to Communism and Nazism (7). Other arguments have evoked shades of the Eugenics movement, or have suggested the drug to be a means of infanticide (7). Part of the liability implicit in any mass-consumption propaganda, no matter what the intended message, is that the general audience is largely uninformed. Given the organization of our media and information networks it is rarely the case that all sides of the story are equally represented; there is such a proliferation of information, it can be difficult to know where to start (8).

 

That being said, for every conservative organization bent on uncovering the evils of RU-486 and abortion, there is a group hoping to win support for the same cause. An interesting feature of the debate surrounding abortion, and likely any similarly politically and emotionally loaded issue, is that both sides, by and large, present the same information: the difference is in the spin. But depending on which side you believe, the other is invariably perceived as being unfairly propagandizing. Whereas one group might lament the risks involved with RU-486, another might point out that these risks are present in any drug or any medical procedure, regardless of the means or the end. Furthermore, in weighing the advantages and disadvantages of a situation, RU-486 may ultimately provide a safer and more reliable option. One source indicates that the one death that occurred following the administration of Mifepristone, the generic name for RU-486, could be attributed to the patient's using the drug despite qualifying for all contraindications (5). This, while tragic, is clearly not a function of the drug, per se. Particularly striking is the statistic indicating that 1 in 3000 women who undergo an illegal abortion will die from the procedure. This is compelling evidence that a controlled means of abortion is significantly less dangerous than an uncontrolled one, in the face of arguments that RU-486 poses too much of a threat to the life of the mother to warrant any generalized use (4). In addition to considering the contraceptive and abortive functions of RU-486, some of the more politically and socially liberal organizations also provide information about the other uses for the drug (1, 6).

 

Considering the efficacy of RU-486, there is evidence that the drug may be valuable in the treatment of breast or ovarian cancer or for use in fighting other tumors (1, 6). This decidedly female slant can be attributed to these illnesses' association with estrogen and progesterone, hormones that can be found in much greater concentrations in women. Similarly, RU-486 is thought to be useful in the treatment of Endometriosis (1, 6), and may provide a viable alternative to risky and only moderately successful surgery. RU-486, by virtue of its role as a glucocorticoid antagonist, holds potential as a treatment for more universally damaging diseases. Of particular and current interest is the inclusion of RU-486 in the treatment of HIV. Through its affinity for the glucocorticoid pathways, RU-486 functions to inhibit viral replication by blocking the protein implicated in facilitating this process (6, 9). Researchers caution that this mechanism is in its earliest stages of development, and may yet prove to have other deleterious effects stemming from its relationship to fundamental hormonal pathways in the body (9). However, preliminary evidence is compelling. An additional link between RU-486 and AIDS comes in the suppression of the Kaposi's Sarcoma that affects a large of AIDS-sufferers. Having shown Kaposi's Sarcoma to be glucocorticoid-mediated through a direct administration of Dexamethasone, researchers then observed RU-486 to be quite effective in stemming the propagation of Kaposi¹s cells (10).

 

One disorder that epitomizes the human stress-response gone wrong is Cushing's Syndrome. It is caused by the hypersecretion of the glucocorticoid cortisol, which plays many vital roles in the upkeep of the body, mostly aimed at general regulatory and homeostatic maintenance (11). Cortisol levels in a normally functioning individual increase during stress as a means of returning to status quo after the threat has passed. When the concentration of cortisol in the body is significantly altered, often due to varying types of tumors in the case of Cushing's Syndrome specifically, the result is a prolonged and unchecked stress response (11). The implications of this are clear, given the risk involved in several of the more debilitating symptoms, such as high blood pressure, muscle and bone weakness, and hyperglycemia (11). Furthermore, the potential benefits that a glucocorticoid antagonist such as RU-486 might provide cannot be ignored (1, 2, 6, 12), offering relief from symptoms by a means alternative to surgery. However, this like many other new applications of the drug is still in the investigative stages (12), and more research is needed to work out the details.

 

Regardless of what is uncovered about RU-486's capabilities scientifically, it isn't likely that it will be quietly assimilated into the medical establishment given the ways in which it has already proven itself to be effective. Even noting its potentially wide application, it cannot be universally advantageous. Imagine, for example, a woman who has come to rely on the drug for treatment of Cushing's Syndrome but who would also like to have children. And there will always be groups who absolutely oppose the use of RU-486 as an abortifacient. It is also not yet clear due its relatively recent development what any prolonged effects of the drug might turn out to be. Even as a means of terminating pregnancy, it is not completely effective and potentially comes with side effects ranging from unpleasant to dangerous (4, 5). But for some women it may provide a better alternative emotionally than turning first to surgical options. Furthermore, its impact on glucocorticoids, while promising and intriguing, should still be approached with some caution. These hormones are part of an evolutionarily fundamental system that has been compromised somewhat by a rapid modernization of lifestyle, but we can't necessarily predict how our innovative new treatments will interact with more basic regulatory mechanisms.

 

The danger inherent in undertaking a close scrutiny of RU-486 and its various uses is its association with such emotionally charged issues. Few people do not have an opinion about abortion, and it is difficult to even approximate true impartiality. To an extent, this is a self-perpetuating problem with little room for dialogue or education; people tend to gravitate to those with similar opinions and shun that which contradicts their often deep-seeded beliefs about a very personal matter. Even the best efforts at impartiality can be thwarted by creeping convictions. This extends even to a consideration of its relatively speaking more mundane therapeutic applications. However if current research being done with RU-486 proves to be at all fruitful it could be of great use to medicine and its patients. Many of the health problems it has the potential to treat are only now presenting themselves; our modern stressors are proving to tax our existing systems in ways and time frames not accounted for in the original evolutionary design. With time and information, hopefully a compromise can be reached allowing RU-486 to evolve into a useful drug.

WWW Sources

1) Endometriosis Research Center: RU-486 Explained

2) RU 486 Research Forges on, Despite Political Hurdles

3) Mechanism of Glucocorticoid Action

4) National Right to Life Committee Statement on RU-486

5) Religious Tolerance: RU-486

6) Feminist Majority Foundation Reports on Mifepristone

7) Unleashing the Killer Pill: RU-486 Dangers, Lies, and Nazi/Communist Roots Exposed

8) The RU-486 Files

9) Penn Scientists Identify New Pathway in HIV Cycle

10) AIDS-related Kaposi¹s Sarcoma: evidence for direct stimulatory effect of glucocorticoid on cell proliferation

11) Cushing¹s Syndrome

12) Treatment of Cushing¹s Syndrome

13) Time Magazine: The Pill Arrives

 

 

Comments made prior to 2007

I know some might not agree with what I have to say here but...

In regards to abortion issues, I think it should be a decision that should be voted on by women and only by women. I mean, how long have men been telling women what they can and cannot do with their own bodies, along with legislating laws to enforce those rules?

Also, in regard to the abortion pill RU-486. I would love to know who named that pill for that person should be commended. I don't know if it was out of an act of some guilt or remorse in having to be part of such a research and development project, to know that by your work there will be many deaths, but that they should give the woman taking it one last chance to take pause and reflect on the situation before going into it blindly.

The term "RU-486" is poignant in that it asks an ethical question of, "Are You For Murder?" To "86" someone is a prison slang term for murder and here the person is asked this question before taking this pill which will then start a process of eliminating a developing life from continuing.

I am not arguing or debating that a fetus or whatever stage this pill is effective at IS in fact a human being or has a soul or in anyway living. What I am merely stating here is that this clever play on letters and numbers is a very deep question indeed, conveinently snuck in yet clear to understand when someone like myself points it out. I actually took a step back and said, "Whoa?!" when I read it and I only figured it out because I love doing those word puzzles in the Sunday paper as well as playing the "license plate" game when on road trips. It's where you see a license plate and tell the other person you are thinking of phrase or theme based on it... (ex. 4U2LUV, 2FAST4U, etc.).

Anyway, I just wanted to share and tell you women, "PLEASE, elect one of your own for President in this country next term. Men have really messed things up these past few thousand years!!!" ... John Macedo, Jr., 28 April 2006

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In April 1980, as part of a

In April 1980, as part of a formal research project at Roussel-Uclaf for the development of glucocorticoid receptor antagonists, chemist Georges Teutsch synthesized mifepristone (RU-38486, the 38,486th compound synthesized by Roussel-Uclaf from 1949 to 1980; shortened to RU-486)
It's too bad you do not put as much time into research as you do making up stories about the name.

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