Who Invented Testosterone?
by Benjamin Bunting BA(Hons) PGCert
Written by Ben Bunting: BA, PGCert. (Sport & Exercise Nutrition) // British Army Physical Training Instructor // S&C Coach.
The body's hormone system uses a "lock-and-key" mechanism, whereby the hormone flows through the blood and targets cells that have receptor sites for it.
Testosterone is a male androgen that's produced primarily by the testicles in adult men. It helps to promote sperm production and sex drive, regulates bone mass and muscle growth and increases strength.
Butenandt, Laquer & Hanisch
Testosterone is a powerful androgen hormone which mainly is secreted by the testicles of males but also small amounts are secreted by the ovaries of females. It is one of the most important steroid hormones and has major impact on physiology, psychology, and reproduction.
The hormone testosterone (androstan-3a-ol-17-one) is one of the most important steroid substances. It determines a man’s phenotype, physiology and psychology. It is also the driving force for reproduction and has a major impact on society, culture and politics.
The testes are one of the earliest endocrine glands and therefore their effects became known quite early in history. This is due to their exposed position and the fact that they are very vulnerable, easily accessible to external manipulation including forceful removal. Castration – leading to loss of virility and fertility – was used over centuries for the punishment of criminal acts and high treason, creation of slaves and servants and preservation of soprano voices for musical entertainment.
Moreover, testis transplantation was widely used to treat hypogonadism and prostate cancer. However, it was not without its risks and side-effects.
A great breakthrough in steroid biochemistry occurred at the National Institute of Medical Research in London and at the Bavarian Academy of Sciences in Munich in 1932 when a consensus was reached on steroid structure: steroids had four rings and the fourth ring contained five C-atoms. This was the first step toward a more precise description of steroid biochemistry and towards a better understanding of the hormone’s properties.
In 1935, the scientists Ernst Laqueur and his group at the University of Amsterdam and Organon isolated and synthesised 10 mg of a new steroid 17b-hydroxy-4-androstene-3one which they baptised 'testosterone'. This sex steroid was then added to the array of sex steroids discovered in the past by Butenandt and Hanisch as well as by Ruzicka and Wettstein.
Although testosterone has an unknown origin, it was first identified in 1935 by Butenandt and Hanisch, although there were others were involved in the constant research and quest for synthesis during this era. They described the synthesis of testosterone in an August 1935 research paper and published a patent for it in that year.
This discovery was a turning point in endocrinology and opened the door to experimental and applied research. Extirpation and transplantation of endocrine glands, including the testes, was well-known since antiquity, but it took some time until these techniques could be used for clinical endocrinology (Cussons & Cusson 2002).
The earliest attempts to use extracts from endocrine glands in medicine were made by Charles-Edouard Brown-Sequard who attempted to inject testicular juice extracts on himself without success, probably at least partially due to a placebo effect. Other experiments involving testes were carried out by Lydston and Lespinase and Voronoff earlier on in the 1920s.
These early experiments led on from the emergence of organotherapy as a popular medical fad in the late 1800s. Testis extracts were injected into the abdomen or other parts of the body for treatment of various ailments.
Research, Synthesis and Isolation of Testosterone
Testosterone is the most important endocrine hormone in the human body and plays a significant role in many different aspects of physiology, morphology and psychology. It is also one of the main driving forces for reproductive success and a key factor in social and cultural development.
The discovery of testosterone was not an easy task and took a long time. It was only at the beginning of the 20th century that research on testosterone and its production became a focus for academic research and industrial enterprise.
Early researchers, especially those studying the sex glands, started to recognize that the testes were the source of testosterone and that this hormone had a large influence on the development of males. This knowledge was put to use in the practice of medicine and, in particular, in the treatment of hypogonadism.
In order to study the testicular glands in detail, it was necessary to isolate testosterone-producing cells called Leydig cells from cultured rats. These cells exist in the interstitium of the testis near the seminiferous tubules and are responsible for testosterone synthesis. They can be isolated from the testes of young and old rats.
Leydig cells are characterized by polygonal cell shape with a large round nucleus, eosinophilic cytoplasm, and abundant lipid content. They have features of steroid-secreting cells, including smooth endoplasmic reticulum and a high number of mitochondria with tubulovesicular cristae. In addition, they have a high number of cyclic nucleotide phosphodiesterases (CNPDS), a family of enzymes that convert steroid precursors to steroids.
Charles-Edouard Brown-Sequard and Testosterone
The bicentenary of Charles-Edouard Brown-Sequard’s birth in Mauritius is a time to reflect on his unique, quixotic and eccentric life. He is best known as the first neurophysiologist to describe hemisection of the spinal cord in sugarcane harvesters’ injuries, but he was a world-class explorer, scientist and entrepreneur who lived in five countries on three continents and crossed the Atlantic 60 times.
His enigmatic oeuvre of scientific discovery is so vast that it would require several lifetimes to fully appreciate his contribution. The most important discovery was of course the symptom of spinal hemisection that is still used as a diagnostic tool.
Yet his contributions to medicine and neuroscience were far more extensive than this. He contributed more than 500 papers, was a member of the French Academy, and had a most coveted post at Paris’s College de France.
He was also a pioneer of endocrinology. Nevertheless, his reputation was marred by a sensational experiment that he carried out late in his career.
He regularly self-administered testicular extracts from dogs and guinea-pigs, which he claimed rejuvenated him and increased his vitality. Despite the fact that this treatment was never replicated, it led to the widespread use of testicular extracts in Europe and North America for several decades. It is now widely believed that the ageing process in men is a partial androgen deficiency (or “andropause”), and testosterone therapy is claimed to improve well-being in middle-aged and elderly men.
Hypogondal Therapy Development
The male hormone testosterone has an important impact on the physiology of the human body. It is the driving force for sexual reproduction, carries signals to the brain and plays an important role in the maintenance of bone mass and tissue integrity. Testosterone is also the primary hormone in blood vessels and is a powerful anabolic.
Although the importance of the testes in regulating homeostasis had been recognized for millennia, scientific exploration of their endocrine function only started in about a century.
In the beginning of the twentieth century, however, testicular implantation became a promising form of therapy for hypogonadal and ageing males. Proponents claimed that it increased longevity, slowed senility, reduced arteriosclerosis, cured chronic skin conditions, boosted individual efficiency, and tackled malnutrition.
American urologist G. Frank Lydston (1858-1942) from Chicago became a leading proponent of this method in the early 1900s and was involved in many of the first clinical trials. He published numerous case reports on testicular implantation in journals such as the Journal of the American Medical Association and wrote extensively about venereal diseases and the American eugenics movement.
Testosterone is the most important and influential hormone in a man’s life. It is responsible for the physiology and psychology of a man, it drives his reproduction and it has an impact on society, culture and politics.
The effects of testosterone are very different in men and women. They affect the phenotype, physiology and psychology of both genders as well as their sexual behaviour. It is also very important for physical development and the functioning of the endocrine system in general.
Until the 20th century, it was not possible to isolate and use testosterone for clinical purposes. It was not until 1935 that the synthesis of this hormone was achieved and only then it became available as a powerful medication for hypogonadism.
In 1939, Butenandt and Ruzicka received the Nobel Prize in Chemistry for a joint contribution to chemistry. They were awarded the prize for their work on sex hormones, oestrogen, progesterone and androsterone.
Butenandt had discovered and isolated the steroid androsterone in 1931 from urine samples given by young policemen in Berlin. He also identified and baptised a new androgenic steroid, 17b-hydroxy-4-androstene-3one, which he extracted from 100 kg of bull testes in 1935.
Butenandt was also able to extract and isolate this hormone from the pancreas of pigs by collaborating with Ernst Laqueur, who had specialised in removing hormones from animal glands at the University of Amsterdam and Organon located next to slaughterhouses in Oss (The Netherlands). This led to the production of pig insulin for the treatment of diabetes.
The chemical discovery of testosterone was a major milestone in the history of medicine. It is the primary hormone that controls male sexuality and growth. It also has many other important effects on the body, including strengthening your heart.
Until about a half-century ago, the idea that a gland might act as a signal transduced by blood circulation was hardly a reality. The concept of hormones emerged in 1902 from physiologists William Bayliss and Ernest Starling, who discovered secretin as a substance that stimulated the flow of digestive juices after it had been released by the pancreas in response to food.
However, in 1927, Fred C. Koch, professor of physiology at the University of Chicago, made use of bovine testicles to study substances the testes released into the bloodstream that produced effects elsewhere in the body. He showed that these substances re-masculinized castrated roosters and pigs and that he could produce a sterile extract of them by placing the testicles in boiling water for a day.
As a result of the success of these experiments, Koch was awarded a Nobel Prize in 1935 for his research on hormones that he had identified by studying testicles of sexless animals. His team's research also led to the synthesis of testosterone, a compound that would soon be widely used as a pharmaceutical.
It was only a few years after the Nobel Prize that testosterone became widely recognized as a sex steroid. This was due in part to the efforts of a Harvard medical professor named Charles-Edouard Brown-Sequard, who had been intrigued by Berthold's observations that he could rejuvenate his own physical and mental abilities by injecting himself with testicular extracts. He and other scientists developed a range of organotherapy techniques that included vaso-ligation, tissue grafts and cellular injections.