15.6.1.8: Progesterone

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Progesterone is one of the steroid hormones. It is secreted by the corpus luteum and by the placenta and is responsible for preparing the body for pregnancy and, if pregnancy occurs, maintaining it until birth.

Corpus luteum: Progesterone secretion by the corpus luteum occurs after ovulation and continues the preparation of the endometrium for a possible pregnancy. It also inhibits contraction of the uterus and inhibits development of a new follicle. If pregnancy does not occur, secretion wanes toward the end of the menstrual cycle, and menstruation begins.
Placenta: If pregnancy does occur, the placenta begins to secrete progesterone which supplements that of the corpus luteum. In fact, by the fifth month of pregnancy, the placenta secretes sufficient progesterone by itself that the corpus luteum is no longer essential to maintain pregnancy.

Progesterone, like all steroids, is a small hydrophobic molecule. Thus it diffuses freely through the plasma membrane of all cells. However, in target cells, like those of the endometrium it becomes tightly bound to a cytoplasmic protein the progesterone receptor. The complex of receptor and its hormone moves into the nucleus. There it binds to a progesterone response element, which is a specific sequence of DNA in the promoters of certain genes that is needed to turn those genes on (or off). Thus the complex of progesterone with its receptor forms a transcription factor.

Progestins

Progestins are synthetic modifications of the progesterone molecule. Several different ones are prescribed

for birth control pills
for hormone replacement therapy (HRT) to reduce the unpleasant symptoms of the menopause
to treat young women who cease to menstruate normally
to prevent premature birth

Some examples:

norgestrel (Trade name = Orvette®) - used as an oral contraceptive
levonorgestrel
- the ingredient in "Plan B", an oral contraceptive taken after unprotected intercourse.
- released from Mirena®, an intrauterine device (IUD).
norethindrone (Trade name = Aygestin®; used in HRT (hormone replacement therapy)

Norethisterone.svg.png — Figure 1: Norethisterone is one of the most widely used progestins. (Public Domain; Fvasconcellos).

RU-486

RU-486 (also known as mifepristone) is a synthetic steroid related to progesterone. Unlike the progestins discussed above, that mimic the action of progesterone, RU-486 blocks the action of progesterone. Synthetic molecules that mimic the action of a natural molecule are called agonists; those that oppose it are antagonists. RU-486 is a progesterone antagonist. It binds to the progesterone receptor, and in so doing prevents progesterone itself from occupying its receptor. Thus the gene transcription normally turned on by progesterone is blocked, and the proteins necessary to begin and maintain pregnancy are not synthesized. If RU-486 is taken shortly after intercourse, it prevents pregnancy. If taken early in pregnancy, it causes the embryo to be aborted. This result has caused RU-486 to be widely used in Europe to terminate early pregnancy. It has not found widespread acceptance in the U.S.