Testosterone, dihydrotestosterone and oestradiol levels in postmenopausal breast cancer tissues

Recchione, C; Venturelli, Elisabetta; Manzari, Antonia; Cavalleri, A; Martinetti, Antonia; Secreto, Giorgio

doi:10.1016/0960-0760(95)00017-t

Cited by 94 publications

(75 citation statements)

References 42 publications

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“…The role of another class of steroids, androgens, has been extensively investigated in breast cancer in human and mouse (Labrie et al 1992, Pasqualini 1993, Sato et al 1993, Recchione et al 1995, Birrel et al 1998 and their specific stimulatory and/or inhibitory actions on growth have been described for several breast cancer cell lines (Poulin et al 1988, Tanaka et al 1992, Birrel et al 1995.…”

Section: Introductionmentioning

confidence: 99%

Role of androgens in proliferation and differentiation of mouse mammary epithelial cell line HC11

Baratta

Grolli²,

Poletti

et al. 2000

Journal of Endocrinology

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Androgens have been found in mammary epithelium and in milk throughout the cycle of the mammary gland in vivo. The aim of this study was to investigate the possible role of these substances in mammary epithelial growth and differentiation in the mouse HC11 cell line. Cells were stimulated with testosterone, dihydrotestosterone, androstenedione and 5 -androstane-3 ,17 -diol at concentrations ranging between 0·3 nM and 30 nM. Cyproterone acetate or flutamide, androgen receptor antagonists, (3 µM) were used to block specific androgen effects. Proliferative effects were measured by an MTT (tetrazolium blue) conversion test and [ 3 H]thymidine uptake. HC11 cells were transfected with p cCAT, a chimeric rat -casein gene promoter-chloramphenicol acetyl transferase (CAT) gene construct and CAT ELISA was used to determine gene expression. RT-PCR was performed to detect androgen receptor expression. After 24, 48 and 72 h androgens significantly (P<0·05) increased proliferation. Androgen antagonists significantly (P<0·05) reduced the proliferative effects. Furthermore androgens potentiated the lactogenic effect of prolactin, insulin and dexamethasone (P<0·05). Finally, the androgen receptor gene was expressed in both proliferating and differentiated HC11 cells. These observations lead us to hypothesize an activity of this class of steroids in mammary physiology. In particular, androgens stimulate cell proliferation and -casein gene expression; this influence appears to be mediated by androgen receptors.

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Section: Introductionmentioning

confidence: 99%

Role of androgens in proliferation and differentiation of mouse mammary epithelial cell line HC11

Baratta

Grolli²,

Poletti

et al. 2000

Journal of Endocrinology

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“…Among the androgens, DHT binds with the highest affinity to androgen receptor (AR), and together with testosterone promotes AR transcriptional activity, while A4 and DHEA have extremely low binding affinity for AR (Avancès et al 2001). Potent androgen DHT concentrations were significantly higher in breast carcinoma tissues than in plasma (Recchione et al 1995), and the tissue concentration of DHT was three-fold higher in ductal carcinoma in situ of the breast compared with the non-neoplastic breast (Shibuya et al 2008). The analysis of serum DHT concentration in the patients of endometrial carcinoma was reported (Audet-Walsh et al 2011), but not in the cases of DHT concentration in endometrial tumor tissues.…”

Section: Intracrinologymentioning

confidence: 99%

“…Therefore, aromatase could be a negative regulator for in situ production of DHT in endometrial carcinoma tissues by possibly reducing concentration or availability of the precursor testosterone and/or A4. Of particular interest, in breast carcinoma, which has estrogen-dependent growth similar to endometrioid endometrial carcinoma, intratumoral concentration of DHT was significantly correlated with that of testosterone (Recchione et al 1995), and aromatase expression was inversely correlated with intratumoral DHT concentration (Suzuki et al 2007) suggesting the functional possibilities of such a hypothesis and its potential relevance in endometrial carcinoma.…”

Section: α-Reductasementioning

confidence: 99%

In situ androgen and estrogen biosynthesis in endometrial cancer: focus on androgen actions and intratumoral production

Itō¹,

Miki²,

Suzuki³

et al. 2016

Endocrine-Related Cancer

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In situ estrogen biosynthesis is considered to play pivotal roles in the development and progression of human endometrial carcinoma. However, the biological roles of androgen have remained virtually unknown. Various epidemiological studies have revealed that elevated serum androgen levels are generally associated with an increased risk of developing endometrial carcinoma; however, studies directly examining androgens in carcinoma tissues are relatively rare and reviews summarizing this information are scarce. Therefore, we summarized recent studies on androgens in endometrial carcinoma, especially focusing androgen actions and in situ androgen biosynthesis. Among the enzymes required for local biosynthesis of androgen, 17β-hydroxysteroid dehydrogenase type 5 (conversion from androstenedione to testosterone) and 5α-reductase (reduction of testosterone to dihydrotestosterone (DHT)) are the principal enzymes involved in the formation of biologically most potent androgen, DHT. Both enzymes and androgen receptor were expressed in endometrial carcinoma tissues, and in situ production of DHT has been reported to exist in endometrial carcinoma tissues. However, testosterone is not only a precursor of DHT production, but also a precursor of estradiol synthesis, as a substrate of the aromatase enzyme. Therefore, aromatase could be another key enzyme serving as a negative regulator for in situ production of DHT by reducing amounts of the precursor. In an in vitro study, DHT was reported to exert antiproliferative effects on endometrial carcinoma cells. Intracrine mechanisms of androgens, the downstream signals of AR, which are directly related to anticancer progression, and the clinical significance of DHT-AR pathway in the patients with endometrial carcinoma have, however, not been fully elucidated.

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“…Contrariamente, algumas evidências de estudos experimentais em primatas têm sugerido a possibilidade de uma plausível proteção (Zhou et al, 2000). Na mesma direção está o fato de que os receptores androgênios são encontrados em cerca de 50% dos tumores de mama, estando associados à sobrevida maior em pacientes operadas de câncer de mama e com uma resposta mais favorável à hormonoterapia em pacientes com doença avançada (Bryan et al, 1984;Recchione et al, 1995). Aguardam-se estudos conclusivos a respeito.…”

Section: Como Empregar Os Androgêniosunclassified

Síndrome de insuficiência androgênica: critérios diagnósticos e terapêuticos

Fernandes¹,

Rennó

Nahás³

et al. 2006

Rev. psiquiatr. clín.

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ResumoA síndrome da insuficiência androgênica na mulher (SIA) desperta, mesmo nos dias atuais, muitas discussões e encerra muitas controvérsias. Sabe-se, no entanto, que os níveis plasmáticos de testosterona declinam progressivamente ao longo do período reprodutivo. Conceitua-se a SIA como o conjunto de sintomas clínicos, a presença de biodisponibilidade diminuída de testosterona e os níveis normais de estrogênios. Entre os principais sintomas, citam-se o comprometimento do bem-estar, o humor disfórico, a fadiga sem causa aparente, o comprometimento do desejo sexual, o emagrecimento e a instabilidade vasomotora em mulheres pós-menopáusicas sob terapêutica estrogênica. Esses sintomas, no entanto, são potencialmente atribuíveis a diferentes etiologias e dificultam o correto diagnóstico na maioria dos casos, ainda que ele seja lembrado com freqüência em pacientes que se submetem à ooforectomia bilateral. O diagnóstico da SIA parece ser essencialmente clínico, não havendo a necessidade das dosagens laboratoriais para a sua comprovação. Não se deve indicar a terapêutica androgênica (TA) em pacientes que não estejam adequadamente estrogenizadas. Considera-se a testosterona o hormônio ideal para a TA. As pacientes com sintomas sugestivos de SIA, excluídas outras causas identificáveis, especialmente se pós-menopáusicas, são candidatas à TA. Não existem dados de segurança sobre a TA em usuárias em longo prazo. A via transdérmica -através de adesivos, cremes e gel -parece ser preferível à oral.Palavras-chave: Deficiência androgênica, terapêutica androgênica, disfunção sexual feminina.

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Testosterone, dihydrotestosterone and oestradiol levels in postmenopausal breast cancer tissues

Cited by 94 publications

References 42 publications

Role of androgens in proliferation and differentiation of mouse mammary epithelial cell line HC11

Role of androgens in proliferation and differentiation of mouse mammary epithelial cell line HC11

In situ androgen and estrogen biosynthesis in endometrial cancer: focus on androgen actions and intratumoral production

Síndrome de insuficiência androgênica: critérios diagnósticos e terapêuticos

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