May 12th, 2005

This is your brain. This is your brain fried in curiosity.

When last I posted about chemistry, I was expressing curiosity about prostaglandins. I had run across that word several too many times in the course of reading about pregnancy and childbirth. It made me suspicious. Especially when I tried to learn about it via google and got progressively more confused. Today, I went to a couple branches of University Books (including the Health Sciences one) and a library (the Health Sciences Library) and attempted to find the picture that R. and I want.

To revisit: we want a diagram that shows the prostaglandins, their precursors, analogs, synthetics, antagonists, etc. and how they interact. Ideally, throughout the body, because in addition to the whole female reproductive system stuff, we're finding out that prostaglandins are involved in cancer, bone resorption, inflammation, platelet activation, fever, smooth muscle (which is inside every organ except the heart), vascular stuff. . .

It's important to stay focused here. It turns out that I was wrong when I concluded this must be an endocrine thing, since, after all, prostaglandins are hormones. New words are showing up every time I do a new search. There's a paracrine system, which is signaling that doesn't go through the blood, but rather directly to neighboring cells (think inflammation and it sort of makes sense). There's an autocrine system, which is a cell talking to itself (think cancer). Prostaglandins are eicosanoids (along with thromboxanes and leukotrienes) that do that kind of stuff. Eicosanoids come from arachidonic acid (which F. pointed out), which in turn are fatty acids. So we've now dragged in all that polyunsaturated stuff like omega-3s and omega-6s. Full-blown conspiracy theory is now appropriate.

Because of the widespread use of these suckers, and because they don't travel far as individuals before breaking down (we're talking cell diameters here, not how many times does it cycle around before you pee it out), the diagram R. and I would like to have is probably years, if not decades, in the future, and won't likely fit on a single page. Honestly, we'll be lucky to see it in decades, because right now research in this area is being funded and driven with a view to new drugs. The best drugs are those that can be taken orally, and get to where they are going via the blood. Which is not a paracrine thing to do. Further, any drug that interacts with these systems effectively risks (ha! never mind risks. Look at all the COX-2 drugs that just got pulled from the market) affecting systems all over the body in very unexpected ways. Further, some of these systems are only active part of the time (when a woman is pregnant, say, or when someone has cancer, or a particular disease or inflammation process is in progress), so if you tested healthy males you'd never, ever, ever see a reaction that might be quite common in another population.

So while I still don't understand what's going on, I'm developing a much better basis for understanding why the drugs coming out of this research are unexpectedly dangerous. We'll see what tomorrow brings. Today's relevant revelation was that mifepristone is a progestogen antagonist -- a really effective one. Grabs all the receptors and does not trigger them at all. Not necessarily a big thing, unless the body currently is trying to use progestogens to moderate, say, uterine contractions. Which mifepristone can turn right off (not the contractions -- the moderation of the contractions). Dump a little misoprostol in with it (which there is an ACOG protocol for use in inducing labor), and you now have the equivalent of a car that has an accelerator and no functioning brakes. Point it downhill and voila, uterine rupture. This is so -incredibly- irresponsible. If the descriptions in the texts presented this as interlocking feedback control systems (which they are), people would be cautious about them. But they don't. The mifepristone is described as "sensitizing" the uterus and the misoprostol as "inducing" labor. Doesn't really suggest interlocking, feedback driven control system, does it?

Despite the fact that they've already run up against these weirdly localized systemic problems (abortifacients with cardiovascular complications) in using structural PG analogues, there still seems to be endless excitement about the potential for new drugs in this area targeting the female reproductive system.