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Progesterone Willard Allen George Corner Russel E. Marker William Allen and George Corner (both from University of Rochester) are credited with isolating and purifying Progesterone in 1933 from human placenta (although there were other scientists that heavily contributed to these efforts). Shortly after its isolation pharamecetical companies generated estrogen extracts to help woman prone to miscarriages keep their pregnancy. However, this process of extraction proved to be expensive and inefficient. In 1943, Russel Marker (Parke-Davis pharmaceutical company) determined a way to synthesize Progesterone from the plant sterol diosgenin which can be efficiently isolated from the Mexican yam. A total synthesis was later elucidated by William S. Johnson (Stanford) in 1971.
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Progesterone – The Pregnancy Hormone
A pregnant raccoon Produced in the ovaries, adrenal glands and placenta (during pregnancy). Produced in small quantities in men ( pg/mL) and changes in women with the stages in menstrual cycle (changes from 2-5 ng/mL more than 20x more in women than men). When a woman is pregnant, progesterone levels sky rocket to ng/mL! Works by binding to progesterone receptors (and sperm cells) through a non-genomic mechanism. It’s effects are more pronounced in the presence of Estrogens.
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Effects of Progesterone
Controls the ability of a woman to get pregnant. Decreases the maternal immune response to allow for the acceptance of the pregnancy. Progesterone decreases contractility of the uterine smooth muscle. Inhibits lactation during pregnancy. The fall in progesterone levels, following delivery, triggers milk production. A drop in progesterone levels is possibly one step that facilitates the onset of labor. It raises epidermal growth factor-1 levels used to sustain cultures, of stem cells. It increases core temperature. It normalizes blood clotting and vascular tone, zinc and copper levels, cell oxygen levels, and use of fat stores for energy. Live shot of baby in womb
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Russel Marker’s Synthesis from Diosgenin
Using this synthesis, Marker was able to make large amounts of progesterone from “dirt cheap” Mexican yam diosgenin! This was a huge breakthrough in medicine at the time. Mexican Yam
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Birth Control Carl Djerassi Birth control pills are made up of molecules that mimic progesterone and fool a woman’s body into thinking she is pregnant. Ultimately, it prevent ovulation from occurring therefore there is no egg to be fertilized. Levels of progesterone mimics vary in birth control and after about a month, it depletes to 0 causing menstruation.
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Legends of Steroidal Chemistry: Adolf Butenandt
Adolf Butenandt (German citizen 1903 – 1995) was undoubtly one of the greatest scientist-pioneers in steriodal chemistry realm. He isolated oestrone, testosterone, estradiol, progesterone, cortisone, and androsterone and in addition to finding synthesis to generate many on these hormone. In 1936, Butenandt was in favor of joining the Nazi party and in doing so financially benefited tremendously from the 3rd reich regime. Those it is not believed that he himself preformed any cruel experiments, he certainly protected scientist who had. Being a German citizen, in 1939 when Butenandt was awarded the Nobel prize, he was forced to reject it. Later after WWII he reclaimed the award.
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Legends of Steroidal Chemistry: William S. Johnson
Bill Johnson ( , University of Wisconsin – Madison and Stanford University) developed a powerful novel cationic approach to construct the four cyclic ring structure of steroids. Using this method, he and his group were able to construct numerous steriods from inexpensive starting materials. Some common examples are: cholesterol, aldosterone, progesterone, oesterone, testosterone, and corticoid. Although Johnson never received a Nobel prize, his contributions led his to some of the most prestegious award in chemistry including: Roger Adams and the Arthur C. Cope awards; the Award for Creative Research in Organic Chemistry; the Tetrahedron Prize for Creativity in Organic Chemistry; and the Nichols Medal.
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Johnson’s Synthesis of Progesterone
Key reaction: polyene cyclization
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Greek physician depicted on pottery
Bile Salts Jöns Jacob Berzelius Human Bile Greek physician depicted on pottery Human bile has likely been studied since the ancient Egyptian times. Its name stems from ancient Greek medicine who erroneously believed in four different types of bodily fluids: red bile (blood), yellow bile (common bile), black bile (not really a recognized fluid), and phlegm (mucus). The ancient Greeks believed in humorism or that an imbalance of these fluids lead to different emotional characteristics. In 1841, Jöns Jacob Berzelius in credited with first isolating bile salts from serpent bile and their role in the body was largely deduced from the turn of the 19th century to the 1930’s.
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Bile Salts (or Bile Acids) - Function
Taurocholic acid Glycocholic acid Cholic acid Chenodeoxycholic acid Main component of bile (liquid stored in gallbladder and secreted in duodenum) Used for emulsifying fats and fat soluble vitamins to be more readily absorbed through the intestines (they act like soap). About half the cholesterol produced in the liver is converted to bile salts (liver) and they are recycled in the body. Bile also contains cholesterol, bilirubin and biliverdin (all of which are very insoluble in water) and when the ratio of bile decreases, they crystallize to create gall stones (very painful).
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Biosynthesis
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Health and Other Uses Bile Salts are recycled in the body being transported back to the liver after digestion. However, it is believed that foods high in soluble fiber (egg plants, oats, lentils, fruits, nuts, and certain vegetables) actually sequester bile salts ridding them from the body. As a result, foods with water soluble fiber tend to lower cholesterol levels (as cholesterol is used up to make new bile salts). Interestingly , cow bile is now isolated and combined with soap to make effective stain removers.
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