Metabolism of androgens in human benign prostatic hyperplasia: Aromatase and its inhibition

Bartsch, W.; Klein, H.; Stürenburg, Hans-Jörg; Voigt, K. D.

doi:10.1016/0022-4731(87)90354-2

Cited by 18 publications

(5 citation statements)

References 26 publications

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“…Based on the characterized tissue distribution of the isoenzymes, included in this group might be compounds that are able to work on: 1 The placenta: danazol; ethinylestradiol (Blomquist et al, 1984); unsaturated fatty acids, such as oleic, arachidonic, linoleic, and linolenic acid (Blomquist, 1985); periodate-oxidized NADP þ (Mendoza-Hernandez et al, 1987); 14,15-secoestra-1,3,5(10)-trien-15-ynes (Auchus, 1989); spiro-gp-lactones containing the C-18 nucleus (Sam et al, 1995); and chalcones, such as naringenin chalcone and 4 -hydroxychalcone (Le Bail et al, 2001). 2 Human benign prostatic hyperplasia tissue: testolactone (Bartsch et al, 1987). 3 Liver microsomal enzymes: nonsteroidal anti-in£ammatory agents and nonsteroidal estrogens, such as hexestrol, dienstrol, diethylstilbestrol, and zearalenone (Hasebe et al, 1987); and retinoids (13 -cis retinoic acid 49-cis retinoic acid 4 all-trans retinoic acid) (Murray et al, 1994).…”

Section: Pharmacologic Development Of Steroidogenic Enzyme Inhibitorsmentioning

confidence: 99%

Cutaneous Androgen Metabolism: Basic Research and Clinical Perspectives

Chen

Thiboutot

Zouboulis

2002

Journal of Investigative Dermatology

247

176

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The skin, especially the pilosebaceous unit composed of sebaceous glands and hair follicles, can synthesize androgens de novo from cholesterol or by locally converting circulating weaker androgens to more potent ones. As in other classical steroidogenic organs, the same six major enzyme systems are involved in cutaneous androgen metabolism, namely steroid sulfatase, 3beta-hydroxy-steroid dehydrogenase, 17beta-hydroxysteroid dehydrogenase, steroid 5alpha-reductase, 3alpha-hydroxysteroid dehydrogenase, and aromatase. Steroid sulfatase, together with P450 side chain cleavage enzyme and P450 17-hydroxylase, was found to reside in the cytoplasm of sebocytes and keratinocytes. Strong steroid sulfatase immunoreactivity was observed in the lesional skin but not in unaffected skin of acne patients. 3beta-hydroxysteroid dehydrogenase has been mainly immunolocalized to sebaceous glands, with the type 1 being the key cutaneous isoenzyme. The type 2 17beta-hydroxysteroid dehydrogenase isoenzyme predominates in sebaceous glands and exhibits greater reductive activity in glands from facial areas compared with acne nonprone areas. In hair follicles, 17beta-hydroxysteroid dehydrogenase was identified mainly in outer root sheath cells. The type 1 5alpha-reductase mainly occurs in the sebaceous glands, whereby the type II isoenzyme seems to be localized in the hair follicles. 3alpha-hydroxysteroid dehydrogenase converts dihydrotestosterone to 3alpha-androstanediol, and the use of 3alpha-androstanediol glucuronide serum level to reflect the hyperandrogenic state in hirsute women may be a reliable parameter, especially for idiopathic hirsutism. In acne patients it is still controversial if 3alpha-androstanediol glucuronide or androsterone glucuronide could serve as suitable serum markers for measuring androgenicity. Aromatase, localized to sebaceous glands and to both outer as well as inner root sheath cells of anagen terminal hair follicles, may play a "detoxifying" role by removing excess androgens. Pharmacologic development of more potent specific isoenzyme antagonists may lead to better clinical treatment or even prevention of androgen-dependent dermatoses.

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Section: Pharmacologic Development Of Steroidogenic Enzyme Inhibitorsmentioning

confidence: 99%

Cutaneous Androgen Metabolism: Basic Research and Clinical Perspectives

Chen

Thiboutot

Zouboulis

2002

Journal of Investigative Dermatology

247

176

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“…Diese Verknü pfung hä ngt von der enzymatischen Aktivitä t der 17b -Hydroxysteroidoxidoreduktasen (17b -HSOR) ab. Darü ber hinaus bestehen ü ber die Aromatase auch Verknü pfungen zu den Estrogenen, wobei bezü glich der Existenz einer intraprostatischen Aromatase kontroverse Daten vorliegen [15,16].…”

Section: Androgenstoffwechsel In Der Menschlichen Prostatazelleunclassified

Die benigne Prostatahyperplasie - das Ergebnis einer altersbedingten Entgleisung der Androgen-Estrogen-Balance?

Weisser

Krieg

1997

Der Urologe A

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Although human benign prostatic hyperplasia (BPH) is the most common tumor in men, its etiology is still unclear. At present, it is only widely accepted that BPH is under the endocrine control of the testes and strongly associated with aging. Therefore, in the human prostate we describe the impact of aging on the activity of various androgen metabolizing enzymes as well as on the endogenous androgen and estrogen levels. Moreover, the inhibition of 5 alpha-reductase by finasteride (Proscar) will be reported. Among all androgen metabolizing enzymes, within the human prostate 5 alpha-reductase is the most powerful one. Most of the androgen metabolizing enzymes undergo a significant age-dependent alteration. For distinct enzymes, the correlation with age is either negative (e.g. 5 alpha-reductase), or positive. Despite a complex pattern of age-dependent alterations, the dominance of 5 alpha-reductase among all androgen metabolizing enzymes is always maintained. This is underlined by a strong accordance between the age-dependent 5 alpha-reductase activity and the corresponding age-dependent endogenous DHT level. In epithelium, both the 5 alpha-reductase activity and the DHT level decrease with age, whereas in stroma not only the 5 alpha-reductase activity is rather constant over the whole age range but the DHT level as well. In contrast to the relatively unaltered DHT content in the stroma of the human prostate, the estrogen content follows an age-dependent increase. On the other side, in epithelium such a positive correlation between the estrogen level and age is not found. Thus, the age-dependent decrease of the DHT accumulation in epithelium and the concomitant increase of the estrogen accumulation in stroma will lead to a tremendous increase with age of the estrogen/androgen ratio in the human prostate. This could be of pathogenetic importance for BPH development if in fact a balanced androgen/estrogen synergism is necessary for the integrity of the normal human prostate. Finally, it is remarkable that the inhibition of 5 alpha-reductase activity by finasteride (Proscar) is significantly stronger in epithelium than in stroma. Therefore, it is conceivable that the global size-reduction of BPH under finasteride treatment is primarily due to the regression of BPH epithelium.

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“…While several previous studies have demonstrated the presence of aromatase activity in rat prostate (22,23), there are conflicting reports concerning human tissue (24)(25)(26)(27). Thus, we have investigated the capacity of macaque prostatic microsomes to synthesize estrogens by using a highly sensitive assay that we have used extensively in brain (28).…”

mentioning

confidence: 96%

Estrogen and Progestin Receptors and Aromatase Activity in Rhesus Monkey Prostate*

West

Roselli²,

Resko

et al. 1988

Endocrinology

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We examined nuclear estrogen receptors (ER) and progestin receptors (PR) in the rhesus monkey prostate. Tissues were obtained from six intact males, five untreated castrates, six castrates treated with testosterone (T) for 6 weeks, and four castrates treated with estradiol (E2) for 6 weeks. Samples of the caudal lobe were either assayed biochemically for ER or stained immunocytochemically (ICC) with monoclonal antibodies against the ER or PR. Prostates from untreated castrates had significantly more ER than tissues from intact or T-treated castrates. In E2-treated castrates, ER number increased compared to that in intact and T-treated castrates. With ICC, ER was found only in the nuclei of the fibroblasts and smooth muscle cells of the stroma, not the glandular, ductal, or urethral epithelial cells. Intact and T-treated castrates had a very small number of positive cells, while untreated and E2-treated castrates had a significantly increased number of positive ER cells in the fibromuscular stroma. With ICC, PR was absent in intact or T-treated animals and barely evident in untreated castrates, but was significantly increased in the fibromuscular stroma of E2-treated castrates. The histological preparations indicated there was no stromal hypertrophy in the E2-treated castrates, but the E2 treatment did cause dilation of the glandular acini. Aromatase activity was measured in prostatic microsomes with a radiometric assay. Levels were low (3-30 fmol/h.mg protein) compared to those in brain and placenta, and no differences in activity were seen between castrates and T-treated castrates. Our data demonstrate that androgens can suppress the level of nuclear ER in the rhesus prostate, and that E2 treatment of castrates can induce PR in the same cells as those that contain ER. Thus, under appropriate conditions, estrogens could affect the rhesus prostate through a receptor-mediated pathway.

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Metabolism of androgens in human benign prostatic hyperplasia: Aromatase and its inhibition

Cited by 18 publications

References 26 publications

Cutaneous Androgen Metabolism: Basic Research and Clinical Perspectives

Cutaneous Androgen Metabolism: Basic Research and Clinical Perspectives

Die benigne Prostatahyperplasie - das Ergebnis einer altersbedingten Entgleisung der Androgen-Estrogen-Balance?

Estrogen and Progestin Receptors and Aromatase Activity in Rhesus Monkey Prostate*

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