Wednesday, February 11, 2009

Happy Valentine's Day: It's All About The Estrogen Baby!


A comment from "Lab Tips" asked 'what is estrogen inhibitor'. The obvious answer would be that it inhibits estrogen. To understand this and why I was so glad that my boss handled the estrogen inhibitor, you'd have to know what estrogen is.

I'm sure if you're a female, you've at least heard of estrogen (aka estradiol). It is most associated with the menstrual cycle and is one of the hormones in The Pill. Little known fact: both males and females have estrogen! Different functions of course.

The above cartoon represent the different stages of a woman's menstrual cycle. It shows 1) the changes in hormones (i.e. estrogen, progesterone, FSH, GnRH, LH), 2) the development of the egg (ovum), 3) the varying thickness of the uterine lining aka the endometrium (this is what is shed during "my period"). Changes in hormone levels cause a physiological change, like the development or release of the egg. Remember this: the changes in hormone levels and the correct timing of these changes are very important.

Overview of hormone cycle:
First, the pituitary gland sends out follicle-stimulating hormone (FSH). Just like the name implies, FSH stimulates follicles in the ovaries to grow. The follicles release estrogen, which sets off a chain reaction. Estrogen triggers the pituitary gland to secrete gonadotropin-releasing hormone (GnRH), which in turn triggers a rise in the secretion of luteinizing hormone (LH). Estrogen and LH continue to rise, which prompts the uterus to build up its endometrium, the thickened uterine lining, and causes changes in the vaginal mucus that make it a better environment for the sperm.

A rise in LH causes the largest follicle to mature into an ovum, or egg, while the immature follicles dissolve. The egg releases from the ovary (a process called ovulation) and enters a fallopian tube. If it goes unfertilized, the egg eventually dissolves. If sperm are present, the egg may be fertilized in the fallopian tube. Then it travels down into the uterus and implants in the endometrium. After the egg is released, a structure in the ovary known as the corpus luteum produces hormones such as progesterone and estrogen. These hormones help make the endometrium suited for the egg's implantation and cause changes in the uterus to support the egg's growth.

Why am I taking this Pill every day?
When you take the pill every day, you are releasing steady concentrations of estrogen and progestin (which mimics progesterone). This decreases the release of GnRH, and therefore the release of FSH and LH. This restricts the follicles from growing, and by extension, an egg from growing and releasing from the ovary. Essentially, these synthetic hormones trick the ovary into thinking that it's already released an egg. The endometrium still builds in the uterus and is released, but this is known as a "withdrawal" period. It's the body's reaction to the withdrawal of the normal hormonal cycle. This is why a period while on the pill is usually lighter and shorter; the corpus luteum can't grow unless the ovary has released an egg. The progestin may also make it harder for sperm to enter the fallopian tube by making the vaginal mucus thicker.

So, why would I be concerned about estrogen inhibitors?
It does get a bit confusing when you read the above paragraph and think, "well, I'm taking estrogen to prevent pregnancy, shouldn't it follow that blocking estrogen will get me pregnant?" NO! Remember how I stated that the timing of hormone release is vital to the menstrual cycle. Look again at the cartoon above. It is the sharp increase of estrogen and progesterone that precedes the thickening of the uterine lining and the release of the egg. The increase in estrogen is necessary for the egg to survive and be fertilized. When you have constant levels of estrogen in the body like when you are taking the pill, there is never this sharp increase in estrogen concentrations. It's just a trick on your body!

In sum, if my estrogen is inhibited, blocked, or damaged in an irreversible fashion, this means that the lining of my uterus will no longer thicken and it will be a hostile place for eggs to be fertilized. Not that I particularly care about this today, but if I ever want to have kids, I had better stay away from the estrogen inhibitors.

Why am I using an estrogen inhibitor in the lab?
This is a slightly more complicated topic and I'm probably going to save it for another post. Basically, I am making a genetically modified mouse using the cre-lox system. Skin and bones explanation: I am looking to delete a gene of interest in my mouse. Through a little magic, I am able to label gene of interest with a specially tagged estrogen receptor. When I want to delete said gene, I inject an estrogen inhibitor, namely tamoxifen, into the mouse. This blocks the production of my gene.

Some of you may already heard of tamoxifen. In other realms its is used in the treatment of breast cancer. The above description of estrogen deals solely with its function in the menstrual cycle in pre-menopausal women. Estrogen has diverse functions in other parts of the body and differs in pre versus post menopausal women.

For more information see:
http://en.wikipedia.org/wiki/Menstrual_cycle
http://en.wikipedia.org/wiki/Tamoxifen
http://en.wikipedia.org/wiki/Estrogen
http://en.wikipedia.org/wiki/Estradiol

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