Transformation of Male Sex Hormones Into a Substance With the Action of a Female Hormone

Steinach, E.; Kun, Han

doi:10.1016/s0140-6736(00)88745-0

Cited by 66 publications

(21 citation statements)

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“…They injected men with testosterone propionate, 50 mg/injection three times per week with a total of 20 injections, and bioassayed urinary oestrogen before and after. Oestrogen levels were between 0 and 36 rat units before the injections, and after, the maximum measured was 1200 rat units (Steinach & Kun 1937). They concluded that 'male hormone, when injected, must therefore be transformed in the body into this physiological substance, i.e., urinary oestrogen'.…”

Section: Journal Of Molecular Endocrinologymentioning

confidence: 99%

“…The suggestion that C19 androgens might be directly converted to C18 phenolic oestrogens (Zondek 1934, Steinach & Kun 1936, 1937 1962, Townsley & Brodie 1968, Brodie et al 1969 suggesting that aromatase acted on the b-face of the substrate. Three moles each of oxygen and reduced NADPH were consumed per mole of androgens converted to oestrogens by the human placental aromatase (Thompson & Siiteri 1974, 1979.…”

Section: Biosynthesis Of Oestrogens: Aromatase and Its Mechanismmentioning

confidence: 99%

“…The suggestion that C19 androgens might be directly converted to C18 phenolic oestrogens (Zondek 1934, Steinach & Kun 1936, 1937 led to the coining of the term aromatase for this reaction (notably, the authors, after exhaustive searching, have not been able to determine who coined the term aromatase). Because of the interest in the development of oral contraceptives, the Worcester Foundation for Experimental Biology in Shrewsbury, Massachusetts, became a major focus for this work.…”

Section: Biosynthesis Of Oestrogens: Aromatase and Its Mechanismmentioning

confidence: 99%

“…Steinach & Kun then tested the hypothesis that testosterone was a precursor of oestradiol (Steinach & Kun 1936, 1937. They originally demonstrated this conversion in male rats (Steinach & Kun 1936) and then a year later in five men (Steinach & Kun 1937). They injected men with testosterone propionate, 50 mg/injection three times per week with a total of 20 injections, and bioassayed urinary oestrogen before and after.…”

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Celebrating 75 years of oestradiol

Simpson

Santen

2015

Journal of Molecular Endocrinology

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Oestrogens exert important effects on the reproductive as well as many other organ systems in both men and women. The history of the discovery of oestrogens, the mechanisms of their synthesis, and their therapeutic applications are very important components of the fabric of endocrinology. These aspects provide the rationale for highlighting several key components of this story. Two investigators, Edward Doisy and Alfred Butenandt, purified and crystalized oestrone nearly simultaneously in 1929, and Doisy later discovered oestriol and oestradiol. Butenandt won the Nobel Prize for this work and Doisy's had to await his purification of vitamin K. Early investigators quickly recognized that oestrogens must be synthesized from androgens and later investigators called this process aromatization. The aromatase enzyme was then characterized, its mechanism determined, and its structure identified after successful crystallization. With the development of knock-out methodology, the precise effects of oestrogen in males and females were defined and clinical syndromes of deficiency and excess described. Their discovery ultimately led to the development of oral contraceptives, treatment of menopausal symptoms, therapies for breast cancer, and induction of fertility, among others. The history of the use of oestrogens for postmenopausal women to relieve symptoms has been characterized by cyclic periods of enthusiasm and concern. The individuals involved in these studies, the innovative thinking required, and the detailed understanding made possible by evolving biologic and molecular techniques provide many lessons for current endocrinologists. Discovery of oestrogenThe concept that substances secreted by one organ could then be transported internally to another via the blood stream is the underpinning of the field of endocrinology. The 'father of physiology', Claude Bernard, articulated the concept of internal secretion by describing how the liver produces glucose, which then travels to and is utilized by other tissues in the body. This concept underlies studies on the ovaries, which became a focus of investigation later in the century. In 1896, Emil Knauer, a 29-year-old Austrian, excised the ovaries of adult rabbits and then re-implanted pieces into different locations in the same animals (Watkins 2007 Doisy then enlisted a nurse in the obstetrics clinic to supply each pregnant patient with a 1 gal jug and ask for her urine. This provided the needed material but was fraught with difficulties. Suspected to be a bootlegger because of the large jugs of yellow material in his car, one of Doisy's drivers was nearly arrested until he suggested using the sniff test with the response 'My god, it is urine'. Doisy, then being recruited to St Louis University, continued his efforts to purify the active substance. Each extract was tested with a bioassay and its effect on uterine stimulation. Urine, the material of choice for study, was initially extracted with a very large countercurrent apparatus (Fig. 1). Costing the exorbitan...

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Section: Journal Of Molecular Endocrinologymentioning

confidence: 99%

Section: Biosynthesis Of Oestrogens: Aromatase and Its Mechanismmentioning

confidence: 99%

Section: Biosynthesis Of Oestrogens: Aromatase and Its Mechanismmentioning

confidence: 99%

mentioning

confidence: 99%

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Celebrating 75 years of oestradiol

Simpson

Santen

2015

Journal of Molecular Endocrinology

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“…The second tumour was a very much smaller lesion, similar in its histological structure to the cortical lesions reported by Horning and Whittick (1954) (1936) found that the administration of androsterone to rats was followed by an increased excretion of oestrogen in the urine. Steinach and Kun (1937) reported similar results in man following treatment with either androsterone or testosterone propionate. Observations of a similar nature were reported by Callow and Callow (1938) and Foss (1939).…”

Section: Observationsmentioning

confidence: 64%

Carcinogenic Action of Androgens

Horning¹

1958

Br J Cancer

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WHEN Lacassagne (1939) first reported the induction of tumours in mice following repeated injections of testosterone, controversy arose as to the cause of these malignant lesions. Burrows (1945) was among the first to suggest the possibility that androgens might be converted into oestrogen within the body. The biochemical studies of Baggett, Engels, Savard and Dorfman (1956) have demonstrated that under certain conditions this conversion does occur and several workers (Kirkman, 1956; Rudali, Desormeaux and Juliard, 1956;Homburger, Borges and Tregier, 1957) have reported the induction of neoplasia in rodents treated with testosterone.The purpose of this communication is to report the induction of tumours in the albino rat and the golden hamster following prolonged administration of the male sex hormone, and also to discuss and correlate these findings with the object of helping to elucidate this problem. MATERIAL AND METHODSYoung albino rats of undeterminate ancestry bred in this Institute were used exclusively in these experiments. Twenty female rats at the age of 3 days received a weekly subcutaneous injection of 0-5 mg. of testosterone propionate in arachis oil. At 21 days the dose was gradually increased to 1 mg. and after 6 months all the survivors were receiving a weekly dose of 2-5 mg. of the male sex hormone. The injections were continued for 21 months.In another experiment 10 male golden hamsters when 2 weeks old received a similar weekly subcutaneous dose of testosterone propionate. After 16 months all the surviving hamsters were sacrificed and tissues for histological examination were fixed either in aqueous or alcoholic Bouin prior to staining with haematoxylin and eosm. OBSERVATIONSNine rats out of the 20 receiving weekly inoculations of testosterone propionate died within the first 6 months' period of treatment. One likewise died during the eighth month. Between 6 to 8 months after treatment with the male sex hormone all the surviving rats began to develop an hypertrophy of the clitoris which by the end of 12 months had become very pronounced (Fig. 1).Out of the 10 rats which survived a period of 16 months' continuous treatment, one developed a large palpable abdominal lesion. Two months later this animal was killed and at autopsy it was found to possess a large unilateral ovarian tumour. There was no evidence of any secondary growths. The remaining

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The biosynthesis of estrogens

Engel

1957

Cancer

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Transformation of Male Sex Hormones Into a Substance With the Action of a Female Hormone

Cited by 66 publications

References 3 publications

Celebrating 75 years of oestradiol

Celebrating 75 years of oestradiol

Carcinogenic Action of Androgens

The biosynthesis of estrogens

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