The quest

American doctors performed many other odd experiments. The book The Male Hormone tells the story of Professor Fred Koch and his student Lemuel McGee, both employed at the University of Chicago. They cheerfully mashed, extracted, fractionized and distilled thousands of kilograms of bulls’ testicles, in search of the pure male sex hormone. From 40 kg of testicles they obtained 20 mg of impure but active sub­stance. The effort was disproportionate: 40 kg for a few paltry milo — grams, and a narrowly failed attempt to win the Nobel Prize.

In 1929 it was the turn of human beings: a 26-year-old man with scarcely any pubic hair, no moustache or beard and with a high-pitched voice was treated with the substance for 53 days. And lo and behold, he was transformed into a real man! He also developed a normal sex­ual appetite with orgasm and ejaculation. The ultimate proof of the

importance of the male sex hormone! However, disillusion followed, since it would never be possible to obtain enough bulls’ testicles for commercial use. Apart from which the processing of the testicles cost a fortune.

The dynamic German chemist Adolf Butenlandt took a different tack: he worked for the Schering chemical group and collected thou­sands of litres of urine, produced by policemen — over 25,000 litres in all. He knew that this must contain the active substance. Eventually he obtained a few crystals consisting mainly of androsterone, a decom­position product of testosterone.

On 27 May 1935 the chemist Ernst Laqueur succeeded in deter­mining the exact structural formula of the sex hormone. He led an excellent research team at the Organon company, and was also a professor of pharmacology at Amsterdam University. He called the hormone testosterone, and the title of his famous article was ‘On crystalline male hormone from testicles’. Laqueur too had unfortunately

required kilograms of bulls’ testicles. At that point the miracle happened that so many scientists had been hoping for: it was found that cholesterol could be converted synthetically into testosterone. In no time there were several manufacturers. The discovery was the achieve­ment of the chemist Leopold Ruzicka, who worked for the Swiss firm of Ciba. Cod liver oil and sheep’s fat, both rich in cholesterol, became the main raw materials. Butenlandt and Ruzicka were awarded the Nobel Prize in 1939, but Laqueur’s work went unrecognized.

How is testosterone viewed today, and what do scientists know about it? Testosterone is a compound of testis and steroid. Its system­atic name is i7beta-hydroxy-4-androsten-3-on. The blood contains a large store of testosterone, a hundred times more than is found in those places where it should be active. This reserve in the blood is attached to transport proteins, which release it only when there is a demand.

A very large number of animal species produce testosterone, but in all females the amount of testosterone is considerably lower than in males. In the womb testosterone ensures that the embryo develops into a boy and during puberty it is responsible for the appearance of sec­ondary male sexual characteristics (including the breaking of the voice, and the growth of the penis, scrotum, pubic hair and skeletal muscles). After puberty testosterone also maintains the male reproductive appa­ratus, the male body shape and the production of sperm cells. Because it strengthens the muscular system, it is banned from sport. The prin­cipal male hormone also plays a part in men’s balding. In both men and women it ensures a healthy libido and also promotes the growth of female pubic hair. In men testosterone is produced in the adrenal glands and by the Leydig cells in the testicles, between 5 and 7 mg per day in all. In women the production is a tenth of that in men. In women testosterone is produced in the ovaries, in the adrenal glands and fatty tissue. The regulation of testosterone is very complex. It begins in the hypothalamus. From puberty onwards, besides its other functions, the hypothalamus transmits increasing numbers of special signals to the hypophysis. These signals (GnRH, gonadotrophine-stimulating hor­mone) prompt the hypophysis in turn to pass on special signals to the testes by means of fsh — follicle-stimulating hormone — and lh — luteinizing hormone. When the concentrations of fsh and lh are high enough, the testes produce more testosterone. The hypothalamus measures the concentrations of testosterone in the blood; when these exceed a certain level, the hypothalamus transmits a different signal to the hypophysis, so that the production of testosterone is inhibited. Testosterone is broken down in the liver. In both the Leydig and Sertoli cells small quantities of female hormone (oestrogens) are produced from testosterone.

A serious depletion of testosterone is caused, for example, by certain diseases of the hypothalamus and abnormalities in the testicles, for instance in men with Klinefelter’s syndrome, and certain kidney dis­eases. Obese men with diabetes also often have too low a testosterone level (see the following section). If the hormone level is completely nor­mal, there is no point in administering additional testosterone, which only creates additional risks of side-effects such as liver abnormalities and the activation of latent prostate cancer.