Conversion of 19-hydroxy-Δ4-androstene-3,17-dione to estrone by endocrine tissue

Meyer, A. S.

doi:10.1016/0006-3002(55)90395-4

Cited by 200 publications

(29 citation statements)

References 14 publications

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“…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. In 1955, Meyer made the crucial discovery that androstenedione was hydroxylated by the bovine adrenal to yield 19-hydroxyandrostenedione (19-OH-A) (Meyer 1955. Studies on the aromatase reaction were greatly improved by the development by Ryan and Engel of human placental microsomes as a source of high aromatase activity.…”

Section: Biosynthesis Of Oestrogens: Aromatase and Its Mechanismmentioning

confidence: 99%

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: Biosynthesis Of Oestrogens: Aromatase and Its Mechanismmentioning

confidence: 99%

Celebrating 75 years of oestradiol

Simpson

Santen

2015

Journal of Molecular Endocrinology

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“…With the isolation of estrone from adrenal cortical tissue by Beall (17) and the demonstration by Meyer (18) that 19-hydroxy-A4 androstene-3, 17-dione can be converted to estrone by adrenal tissue, it would appear that adrenal cortical tissue has the necessary enzyme systems for synthesizing estrogens and that secretion of estrogens by the adrenal gland is a real possibility. On the other hand, it has been demonstrated that certain C19 neutral steroids of the androgenic series, some of which are produced by the adrenal cortex, are converted to estrogens both in vivo and in vitro by a variety of tissues (18)(19)(20)(21). Under the conditions of the present experiments the adrenal cortex could have secreted these C1, neutral steroids or other unknown precursors which were metabolized in part to estrogens elsewhere in the body and excreted in the urine.…”

Section: Discussionmentioning

confidence: 51%

Adrenal Estrogens in Patients With Metastatic Breast Cancer1

West¹,

Damast²,

Pearson³

1958

J. Clin. Invest.

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“…In premenopausal women it is found mainly in the ovaries and during gestation in the placenta (Meyer 1955, Richards 1994. In men and postmenopausal women, estrogens are produced mainly in fibroblasts from adipose tissue (Simpson et al 1994).…”

Section: Introductionmentioning

confidence: 99%

Progesterone inhibits glucocorticoid-dependent aromatase induction in human adipose fibroblasts

Schmidt

Renner²,

Löffler³

1998

Journal of Endocrinology

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In fibroblasts derived from human adipose tissue, aromatase induction is observed after exposure to 1 µM cortisol in the presence of serum or platelet-derived growth factor (PDGF). Progesterone suppresses this induction in a dose-dependent manner, 10 µM resulting in complete inhibition. A reduced cortisol concentration (0·1 µM) concomitantly reduces the progesterone concentration required for effective inhibition (10-100 nM). This effect of progesterone is specific, as neither the release of cellular enzymes nor aromatase induction by dibutyrylcAMP, which acts independently from cortisol, are affected. However, the inhibitory effect of progesterone requires its presence throughout the induction period. Kinetic studies in intact cells reveal a reduced number of aromatase active sites upon progesterone treatment, whereas progesterone at near-physiological concentration (100 nM) does not inhibit aromatase activity in isolated microsomes. Semi-quantitative reverse transcriptase PCR analysis shows reduced amounts of aromatase mRNA in progesterone-treated cells, indicating specific inhibition of the glucocorticoid-dependent pathway of aromatase induction. The inhibitory effect of progesterone is not blocked by the anti-progestin ZK114043, excluding action via progesterone receptors and indicating competition for the glucocorticoid receptor. Progesterone must be considered a potential physiological inhibitor of glucocorticoiddependent aromatase induction in adipose tissue. It is proposed that it is a suppressor of aromatase induction in adipose tissue in premenopausal women.

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Conversion of 19-hydroxy-Δ4-androstene-3,17-dione to estrone by endocrine tissue

Cited by 200 publications

References 14 publications

Celebrating 75 years of oestradiol

Celebrating 75 years of oestradiol

Adrenal Estrogens in Patients With Metastatic Breast Cancer1

Progesterone inhibits glucocorticoid-dependent aromatase induction in human adipose fibroblasts

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