8. The Discovery of Sex Hormones

From: The 7 Sexes

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8 The Discovery of Sex Hormones In 1902, William Bayliss (1860–1924) and Ernest Starling (1866–1927) introducedtheterm“hormone.”1Hormonesaresubstancesproducedby one organ, an endocrine gland, that acts at a distance on another organ. The field of science that studies this is called endocrinology. The names of hormones were all coined in the twentieth century, but the idea that there was something like hormones has existed since antiquity. For example , Chinese medicine frequently made use of extracts from human urine that were used to treat disease. Sincehumanhistorybeganandmedicaltreatmentswereattempted, physical changes associated with endocrine glands have been known. Castratedmales,sinceantiquityknownaseunuchs,losetheircapacityto growabeard,maydevelopenlargedbreasts,andbecomeeffeminate.Eunuchs have had a long history serving as guards of harems in the Middle East, where plural marriages were common and reflective of wealth and power, and they served as political advisors in the Forbidden City in Beijing during the rule of Chinese emperors. Eunuchs were usually castrated as young men, but a special category of eunuchs were castrated as preadolescent boys. These were called castrati. During the Renaissance and until the eighteenth century, boys in choirs who were aged six to ten and who had a talent for singing and reading music were castrated and groomed to become prized singers because of their “celestial” sopranolikeuppervoicerange .Theydifferedfromtypicaleunuchs,wholosttheir testes as adults, tending to be taller than average and appearing “etiolated ,” with unusually wide hips in an otherwise slender frame.2 Castration was also applied to slaves in Greece about 400 bce because they were considered to be more docile. In Jewish tradition, eunuchs were The Discovery of Sex Hormones 51 excluded from religious ceremonies. Early Christian monks sometimes practiced castration to remove the temptation of sexual attraction.3 There were other indications of necessary body secretions and their effects on human health. Some people developed goiters, which on autopsy revealed the presence of an enlarged thyroid gland. When this occurred in infants it led to a dwarfism and mental retardation called cretinism. Cretins were associated with regions of a country having inadequate iodine in the food and water. Diabetes was recognized as a disease that led to gangrene, coma, and death. People who suffered from diabetes had sugary urine that attracted flies. The hormonal basis of the disease was not known until the twentieth century. Amajorinsightintosexhormonesoccurredin1849,whenArnoldA. Berthold(1803–1861),aGermanphysician,beganaseriesofexperiments on chickens.4 He removed the testes from two of them and they became capons(thechickenequivalentsofeunuchs).Whenhetookanothertwo chickens, removed the testes, and then reimplanted them at a different site in the abdomens of their bodies, they became roosters with a comb on their heads. The control male chickens went on to become typical roosters like those whose testes were reimplanted. From this, Berthold concluded that the testes produced some secretion that was essential for the masculinization of the male chicken as it matured into an adult. The first recognition of a hormone by Bayliss and Starling involved a pancreatic response to a substance secreted by the duodenum. When they introduced the juices of the duodenum into the jugular vein, the pancreas began to secrete. Bayliss and Starling revived the experimental approach to endocrinology that Berthold initiated. It would be another two to three decades before the sex hormones were identified and related to their functions, because an exquisitely small amount of active hormoneisreleasedbyanendocrineorgan,andbecausescientistslacked analyticalchemicaltoolstopurifyorobtainthoseactivesubstances.That changed dramatically with the independent achievements of Adolph Butenandt (1903–1995) and Leopold Ruzicka (1887–1976) working with and synthesizing steroid hormones. In 1929, Edward Doisy (1893–1986) in the United States and Butenandt in Germany first identified a steroid hormone.5 It was an estrogen called estrone. Butenandt identified it as a steroid: a polycyclic molecule with four rings. Ruzicka was studying bilesaltsand relatingtheirpolycyclic compoundstosimilarring-shaped molecules found in coal tars.6 Butenandt and Ruzicka realized that the progenitor of the steroid hormones, which were rapidly being found in the 1930s, could all be derived from a common chemical, cholesterol (Figure 8.1). Thesexhormonesincludedestriol,foundbyGuyFrederickMarrian (1904–1981) in 1930; progesterone, found by George Washington Corner (1889–1981)andWillardMyronAllen(1904–1993)in1933anddesignated bythemas“thehormoneofpregnancy”;andtestosterone,firstisolatedby HO H H 1 2 3 5 4 6 7 8 10 19 9 11 12 13 14 15 16 17 18 21 20 22 23 24 25 26 27 Figure8.1.Thecholesterolmoleculecontainsfourrings,threeofthemsix-carbonringsand one of them a five-carbon ring. The carbons are numbered 1-17. There are ten additional carbon locations (18-27). The various steroid hormones contain different attached side groups. The more numerous the modifications are to the cholesterol base...