1900-1970
1903
Research on human reproduction intensified in the early twentieth century. Ludwig Fraenkel described the corpus luteum, the glandular mass that forms in women’s bodies during the normal menstrual cycle that we now know is supported by hCG during pregnancy. He identified some hormones that had a role in female reproduction, naming the hormone that promoted gestation, progesterone. Progesterone was isolated (an important step in the study of hormones) in 1934.
1920s
Independently, scientists in several laboratories across Europe described the presence of a substance that promotes ovary development and growth in rabbits and mice. In Germany, Selmar Aschheim and Bernhard Zondek noted that this substance specifically affected the formation of the corpus luteum.
Scientists recognized that there is a specific hormone (now known as human chorionic gonadotropin (hCG)) that is only found in pregnant women.
1927
Aschheim and Zondek described a test (known as the A-Z test) which identified the presence of hCG in urine. To test for pregnancy, a woman’s urine was injected into an immature rat or mouse. If the subject was not pregnant, there would be no reaction. In the case of pregnancy, the rat would show an estrous reaction (be in heat) despite its immaturity. This test implied that during pregnancy there was an increased production of the hormone. During early studies of the A-Z test, the scientists discovered that testicular tumors could produce hCG as well.
1930s
Hormone research blossomed in this period. Scientists in several different laboratories developed bioassays (special tests using animals or live tissue) to identify hCG by injecting samples to induce ovulation in rabbits, frogs, toads, and rats. These tests were expensive, required the sacrifice of several animals, and slow, often taking days to get results. The tests were also insensitive when measuring hormone levels to diagnose pregnancy because of the similarity between hCG and another substance, luteinizing hormone (LH). Most bioassays were in fact unable to distinguish between the two except at extraordinarily high rates of hCG.
Herbert Evans discovered that when injected with certain fluids from the female glands a female rat would grow an abnormally large corpus luteum. These fluids were hormones now known as gonadotropins.
In the next few decades laboratory scientists increased their level of interest in the study of human reproduction and on the role of ovaries and testes in human development.
1932
The First International Conference of Standardization of Sex Hormones was held in London, marking the culmination of a decade of increased interest in the chemical properties of sex hormones rather than the previously limited focus on biological function.
1930s-1940s
Popular childbirth books began to encourage women to visit a doctor’s office for confirmation of pregnancy rather than relying on “old wives’ tales” for the diagnosis.
1958
Gonadotropins were first extracted from human pituitary glands.
1960
A “hemagglutination inhibition test” for pregnancy was developed by L. Wide and C.A. Gemzell. Because it used cells in the testing process, this test was an immunoassay rather than a bioassay. The test used purified hCG, mixed with a urine sample and antibodies directed against hCG. In a positive pregnancy test, the red cells clumped, displaying a particular pattern. This test was much faster and cheaper than the old bioassay, but still relatively insensitive, especially for early diagnosis of pregnancy. The test also cross-reacted with various medications.
Mid-1960s
Important disease research in this period led to more knowledge about how hormones, steroids, and antibodies work in the human body. In the next decade, NICHD scientists would transfer these principles to their studies of reproductive hormones such as hCG.
1966
A. R. Midgley described the first radioimmunoassay for hCG, but the test still could not differentiate between hCG and luteinizing hormone. Several other laboratories reported improvements on this test, but did not solve this basic problem.
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