The estrogenic and antiestrogenic activities of androgens in female target tissues.

Rochefort, Henri; Garcia, Marcel

doi:10.1016/0163-7258(83)90013-x

Cited by 110Estrogen and related hormone effectsMale Breast Health StudiesEffects and risks of endocrine disrupting chemicals

The estrogenic and antiestrogenic activities of androgens in female target tissues.

Rochefort, Henri, Garcia, Marcel·1983·Pharmacology & Therapeutics

DOI 10.1016/0163-7258(83)90013-x

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4-Dione also led to significant growth inhibition in ZR-75-1 cells, although the active concentrations (IC50, 15 nM) are in the upper range of the plasma concentrations (1-10 nM) found in women.
“4-Dione also led to significant growth inhibition in ZR-75-1 cells, although the active concentrations (IC 50 , 15 nm) are in the upper range of the plasma concentrations (1-10 nm) found in women (215-218).”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [215]
In ZR-75-1 cells, concentrations of DHT in the incubation medium similar to the plasma levels found in normal women and breast cancer patients (0.3-0.7 nM) are potent inhibitors of the mitogenic effect of E2 and even inhibit growth in the absence of estrogens.
“In ZR-75-1 cells, concentrations of DHT in the incubation medium similar to the plasma levels found in normal women (215-217) and breast cancer patients (Ref.218; 0.3-0.7 nm) are potent inhibitors of the mitogenic effect of E 2 and even inhibit growth in the absence of estrogens (208).”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [215]
The data summarized above clearly support the hypothesis that at least part of the antagonism observed between the action of androgens and estrogens in breast cancer cells may be explained by the heterologous downregulation of the ER by an AR-mediated mechanism.
“The data summarized above clearly support the hypothesis that at least part of the antagonism observed between the action of androgens and estrogens in breast cancer cells (208,211,215,240) may be explained by the heterologous downregulation of the ER by an AR-mediated mechanism.”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [215]
The concentration of DHT needed to exert a half-maximal suppression of ER binding activity (0.07-0.1 nM) is lower than the concentration known to induce binding and nuclear retention of the ER.
“The concentration of DHT needed to exert a half-maximal suppression of ER binding activity (0.07-0.1 nm) is lower than the concentration known to induce binding and nuclear retention of the ER (215, 234).”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [215]

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Relative binding affinity of androstane and c-19-nor-androstane-steroids for the estradiol-receptor in human myometrial and mammary cancer tissue
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Estrogen receptors in androgen-induced breast tumor regression.
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Growth and therapy of mammary tumours induced by 7,12-dimethylbenzanthracene in rats.
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Some hypothesese about interactions between estrogen and androgen and their possible receptors
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ANDROGENIZATION: ALTERATIONS IN THE MECHANISM OF OESTROGEN ACTION
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The histological changes in the sex organs of spayed rats induced by testosterone and œstrone
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THE EFFECT OF ANDROGENS ON THE MAMMARY GLAND OF THE FEMALE RHESUS MONKEY
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Effect of Antibodies to Estrogen Receptor on the Binding of3H-Labeled Antiestrogens and Androstanediol in the Uterus*
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Factors affecting dehydroepiandrosterone sulphate levels in human breast secretions
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Counteraction by Prolactin of Androgen-Induced Inhibition of Mammary Tumor Growth in Rats2
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Insulin Binding to Its Receptor: Is the Receptor More Important Than the Hormone?
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Androgen Control of Cytosol Progesterone Receptor Levels in the MT-W9B Transplantable Mammary Tumor in the Rat 2 3
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Sequential steroid hormone treatment antagonizes the action of estrogen in chick oviduct
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EFFECTS OF TESTOSTERONE PROPIONATE ON THE MAMMARY GLANDS OF FEMALE ALBINO RATS1
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Sex hormone production and action
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STUDIES ON THE UTERINE GROWTH-STIMULATING EFFECTS OF COMBINATIONS OF TESTOSTERONE PROPIONATE AND NATURAL OESTROGENS
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Post-menopausal Estrogen Production
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Mechanism of androgen action on the uterus: influence on the RNA biosynthesis and relationship to the estrogen action.
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5 of the 129 references couldn’t be matched to a known paper.

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Molecular biology of the 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 –isomerase gene family
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Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone
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The role of estradiol in male reproductive function
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Gynecomastia
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Estrogens and their receptors in breast cancer progression: a dual role in cancer proliferation and invasion
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Breast Cancer Development in Transsexual Subjects Receiving Cross-Sex Hormone Treatment
Gooren, L. J., van Trotsenburg, M. A. A., Giltay, E. J., & van Diest, P. J. (2013) · The Journal of Sexual Medicine · doi:10.1111/jsm.12319 · Cited by 246 · see citing works
Stimulation of cell proliferation and estrogenic response by adrenal C19-delta 5-steroids in the ZR-75-1 human breast cancer cell line.
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EAA clinical practice guidelines—gynecomastia evaluation and management
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Androgens inhibit basal and estrogen-induced cell proliferation in the ZR-75-1 human breast cancer cell line.
Poulin, R., Baker, D., & Labrie, F. (1988) · Breast Cancer Research and Treatment · doi:10.1007/bf01805942 · Cited by 172 · see citing works
(S)-(+)-4-[7-(2,2-Dimethyl-1-oxopro- poxy)-4-methyl-2-[4-[2-(1-piperidinyl)- ethoxy]phenyl]-2H-1-benzopyran-3-yl]- phenyl 2,2-Dimethylpropanoate (EM-800): A Highly Potent, Specific, and Orally Active Nonsteroidal Antiestrogen
Gauthier, S., Caron, B., Cloutier, J., Dory, Y. L., Favre, A., Larouche, D., Mailhot, J., Ouellet, C., Schwerdtfeger, A., Leblanc, G., et al. (1997) · Journal of Medicinal Chemistry · doi:10.1021/jm970095o · Cited by 156 · see citing works
RU486, a progestin and glucocorticoid antagonist, inhibits the growth of breast cancer cells via the progesterone receptor.
BARDON, S., VIGKPN, F., CHALBOS, D., & ROCHEFORT, H. (1985) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-60-4-692 · Cited by 143 · see citing works
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MECHANISMS IN ENDOCRINOLOGY: Estradiol as a male hormone
Russell, N., & Grossmann, M. (2019) · European Journal of Endocrinology · doi:10.1530/eje-18-1000 · Cited by 138 · see citing works
Preeclampsia and Breast Cancer Risk
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Down-regulation of estrogen receptors by androgens in the ZR-75-1 human breast cancer cell line.
POULIN, R., SIMARD, J., LABRIE, C., PETITCLERC, L., DUMONT, M., LAGACÉ, L., & LABRIE, F. (1989) · Endocrinology · doi:10.1210/endo-125-1-392 · Cited by 115 · see citing works
Testosterone and 5α-dihydrotestosterone inhibitin vitrogrowth of human breast cancer cell lines
Ortmann, J., Prifti, S., Bohlmann, M. K., Rehberger-Schneider, S., Strowitzki, T., & Rabe, T. (2002) · Gynecological Endocrinology · doi:10.1080/gye.16.2.113.120 · Cited by 100 · see citing works
Estradiol Down-Regulates the Mannose-6-Phosphate/Insulin-Like Growth Factor-II Receptor Gene and Induces Cathepsin-D in Breast Cancer Cells: A Receptor Saturation Mechanism to Increase the Secretion of Lysosomal Proenzymes
Mathieu, M. N., Vignon, F., Capony, F., & Rochefort, H. (1991) · Molecular Endocrinology · doi:10.1210/mend-5-6-815 · Cited by 89 · see citing works
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Causes of gynaecomastia in young adult males and factors associated with idiopathic gynaecomastia
Ersöz, H. Ö., Önde, M. E., Terekeci, H., Kurtoglu, S., & Tor, H. (2002) · International Journal of Andrology · doi:10.1046/j.1365-2605.2002.00374.x · Cited by 85 · see citing works
Power-Assisted Liposuction and the Pull-Through Technique for the Treatment of Gynecomastia
Lista, F. R., & Ahmad, J. (2008) · Plastic & Reconstructive Surgery · doi:10.1097/01.prs.0000299907.04502.2f · Cited by 85 · see citing works
Regulation of Mouse Liver Flavin-Containing Monooxygenases 1 and 3 by Sex Steroids
Falls, J. G., Ryu, D., Cao, Y., Levi, P. E., & Hodgson, E. (1997) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1997.9965 · Cited by 83 · see citing works
Effects of Long-term Androgen Administration on Breast Tissue of Female-to-Male Transsexuals
Slagter, M. H., Gooren, L. J., Scorilas, A., Petraki, C. D., & Diamandis, E. P. (2006) · Journal of Histochemistry & Cytochemistry · doi:10.1369/jhc.6a6928.2006 · Cited by 83 · see citing works
Estradiol stimulates cell growth and secretion of procathepsin D and a 120-kilodalton protein in the human ovarian cancer cell line BG-1
Galtier, F., Capony, F., Maudelondé, T., & Rochefort, H. (1992) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.75.6.1497 · Cited by 82 · see citing works
Self-citation
Relationship of Adolescent Gynecomastia with Varicocele and Somatometric Parameters: A Cross-Sectional Study in 6200 Healthy Boys
Kumanov, P., Deepinder, F., Robeva, R. N., Tomova, A., Li, J., & Agarwal, A. K. (2007) · Journal of Adolescent Health · doi:10.1016/j.jadohealth.2007.03.010 · Cited by 80 · see citing works
Management of gynaecomastia: an update
Gikas, P. D., & Mokbel, K. (2007) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2006.01095.x · Cited by 79 · see citing works
Induction of 3β-Hydroxysteroid Dehydrogenase/Δ5-Δ4 Isomerase Type 1 Gene Transcription in Human Breast Cancer Cell Lines and in Normal Mammary Epithelial Cells by Interleukin-4 and Interleukin-13
Gingras, S., Moriggl, R., Groner, B., & Simard, J. (1999) · Molecular Endocrinology · doi:10.1210/mend.13.1.0221 · Cited by 76 · see citing works
Novel compounds inhibit estrogen formation and action.
Labrie, C., Martel, C., Dufour, J. M., Lévesque, C., Mérand, Y., & Labrie, F. (1992) · PubMed · Cited by 73 · see citing works
Anabolic androgenic steroids and carcinogenicity focusing on Leydig cell: a literature review
Salerno, M., Cascio, O., Bertozzi, G., Sessa, F., Messina, A., Monda, V., Cipolloni, L., Biondi, A., Daniele, A., & Pomara, C. (2018) · Oncotarget · doi:10.18632/oncotarget.24767 · Cited by 71 · see citing works
Intratissular androgens in benign prostatic hyperplasia and prostatic cancer
Voigt, K., & BARTSCH, W. (1986) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(86)90304-3 · Cited by 71 · see citing works
Androstenedione and androst-5-ene-3β,17β-diol stimulate DMBA-induced rat mammary tumors — role of aromatase
Dauvois, S., & Labrie, F. (1989) · Breast Cancer Research and Treatment · doi:10.1007/bf01806551 · Cited by 68 · see citing works
Enzymes of Androgen Formation and Degradation in the Human Prostate
BARTSCH, W., Klein, H., Schiemann, U., Bauer, H. W., & Voigt, K. D. (1990) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1990.tb34282.x · Cited by 67 · see citing works
Identification and androgen regulation of two proteins released by T47D human breast cancer cells.
Chalbos, D., Haagensen, D. E., Parish, T., & Rochefort, H. (1987) · PubMed · Cited by 66 · see citing works
Self-citation
Does Early Physical Maturity Influence Breast Cancer Risk?
Stoll, B. A., VATTEN, L. J., & Kvinnsland, S. (1994) · Acta Oncologica · doi:10.3109/02841869409098400 · Cited by 65 · see citing works
Sex steroids induced up-regulation of 1,25-(OH)2 vitamin D3 receptors in T 47D breast cancer cells
Escaleira, M. T. F., Sonohara, S., & Brentani, M. M. (1993) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/0960-0760(93)90340-3 · Cited by 62 · see citing works
Surgical Management of Gynecomastia: Subcutaneous Mastectomy and Liposuction
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Estrogen and androgen receptor mediated stimulation and inhibition of proliferation by androst-5-ene-3β,17β-diol in human mammary cancer cells
Hackenberg, R., Turgetto, I., Filmer, A., & Schulz, K.-D. (1993) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/0960-0760(93)90187-2 · Cited by 52 · see citing works
A potential role for catecholamines in the development and progression of carcinogen-induced mammary tumors: Hormonal control of β-adrenergic receptors and correlation with tumor growth
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Breast cancer: the obesity connection
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A Novel A10E Homozygous Mutation in theHSD3B2Gene Causing Severe Salt-Wasting 3β-Hydroxysteroid Dehydrogenase Deficiency in 46,XX and 46,XY French-Canadians: Evaluation of Gonadal Function after Puberty1
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Sex hormone-induced mammary carcinogenesis in female Noble rats: the role of androgens
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Inhibitory effect of androgens on DMBA-induced mammary carcinoma in the rat.
Dauvois, S., Li, S., Martel, C., & Labrie, F. (1989) · Breast Cancer Research and Treatment · doi:10.1007/bf01806301 · Cited by 47 · see citing works
Morphological Changes Induced by 6-Month Treatment of Intact and Ovariectomized Mice with Tamoxifen and the Pure Antiestrogen EM-800
Sourla, A., Luo, S., Labrie, C., Bélanger, A., & Labrie, F. (1997) · Endocrinology · doi:10.1210/endo.138.12.5560 · Cited by 46 · see citing works
Combined Effects of Dehydroepiandrosterone and EM-800 on Bone Mass, Serum Lipids, and the Development of Dimethylbenz(A)Anthracene-Induced Mammary Carcinoma in the Rat
Luo, S., Sourla, A., Labrie, C., Bélanger, A., & Labrie, F. (1997) · Endocrinology · doi:10.1210/endo.138.10.5429 · Cited by 44 · see citing works
Adrenal androgens and human breast cancer: A new appraisal
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Crucial role of cytokines in sex steroid formation in normal and tumoral tissues
Simard, J., & Gingras, S. (2001) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(00)00387-7 · Cited by 40 · see citing works
Quality of life as an outcome variable in the management of cancer pain
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Selective conversion by microglia of dehydroepiandrosterone to 5-androstenediol—A steroid with inherent estrogenic properties
Jellinck, P. H., Kaufmann, M., Gottfried‐Blackmore, A., McEwen, B. S., Jones, G., & Bulloch, K. (2007) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2007.04.004 · Cited by 38 · see citing works
Neurosteroids: Synthesis and Functions in the Central and Peripheral Nervous Systems
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Induction of high incidence of mammary tumour in female Noble rats with a combination of 17-oestradiol and testosterone
Xie, B. (1999) · Carcinogenesis · doi:10.1093/carcin/20.6.1069 · Cited by 35 · see citing works
Estrogen Down-Regulation of Androgen Receptors in Cultured Human Mammary Cancer Cells (MCF-7)*
Stover, E. P., Krishnan, A. V., & Feldman, D. (1987) · Endocrinology · doi:10.1210/endo-120-6-2597 · Cited by 35 · see citing works
The proliferative effects of 5-androstene-3β,17β-diol and 5α-dihydrotestosterone on cell cycle analysis and cell proliferation in MCF7, T47D and MDAMB231 breast cancer cell lines
Aspinall, S. R., Stamp, S., Davison, A., Shenton, B. K., & Lennard, T. W. J. (2004) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2003.10.011 · Cited by 34 · see citing works
Combined effects of RU486 and tamoxifen on the growth and cell cycle phases of the MCF-7 cell line
Thomas, M., & Monet, J.-D. (1992) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.75.3.865 · Cited by 34 · see citing works
5-En-androstene-3 β,17 β-diol inhibits the growth of MCF-7 breast cancer cells when oestrogen receptors are blocked by oestradiol
Boccuzzi, G., Brignardello, E., Monaco, M. D., Gatto, V., Leonardi, L., Pizzini, A., & Gallo, M. (1994) · British Journal of Cancer · doi:10.1038/bjc.1994.444 · Cited by 34 · see citing works
Effect of Twenty-Four-Week Treatment with the Antiestrogen EM-800 on Estrogen-Sensitive Parameters in Intact and Ovariectomized Mice
Luo, S., Sourla, A., Labrie, C., Gauthier, S., Mérand, Y., Bélanger, A., & Labrie, F. (1998) · Endocrinology · doi:10.1210/endo.139.5.5994 · Cited by 33 · see citing works
Comparative study of plasma steroid and steroid glucuronide levels in normal men and in men with benign prostatic hyperplasia
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Stanozolol and danazol, unlike natural androgens, interact with the low affinity glucocorticoid-binding sites from male rat liver microsomes
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Androgen, estrogen, and progesterone receptor levels in malignant and benign breast tumors: A multivariate analysis approach
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Do antiestrogens and antiprogestins act as hormone antagonists or receptor-targeted drugs in breast cancer?
Rochefort, H. (1987) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(87)90180-5 · Cited by 29 · see citing works
Self-citation
Nandrolone and stanozolol upregulate aromatase expression and further increase IGF-I-dependent effects on MCF-7 breast cancer cell proliferation
Sirianni, R., Capparelli, C., Chimento, A., Panza, S., Catalano, S., Lanzino, M., Pezzi, V., & Andò, S. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2012.08.002 · Cited by 25 · see citing works
Nandrolone and stanozolol induce leydig cell tumor proliferation through an estrogen‐dependent mechanism involving IGF‐I system
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Marked Increase in Incident Gynecomastia: A 20-Year National Registry Study, 1998 to 2017
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Antiestrogenic action of dihydrotestosterone in mouse breast. Competition with estradiol for binding to the estrogen receptor.
Casey, R. W., & Wilson, J. D. (1984) · Journal of Clinical Investigation · doi:10.1172/jci111654 · Cited by 25 · see citing works
Estrogenic and progestational activity of 7α-methyl-19-nortestosterone, a synthetic androgen
Beri, R., Kumar, N., Savage, T., Benalcazar, L., & Sundaram, K. (1998) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(98)00114-9 · Cited by 22 · see citing works
Metabolism of androgens in human benign prostatic hyperplasia: Aromatase and its inhibition
BARTSCH, W., Klein, H., Stürenburg, H.-J., & Voigt, K. (1987) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(87)90354-2 · Cited by 22 · see citing works
C19 steroids estrogenic activity in human breast cancer cell lines: importance of dehydroepiandrosterone sulfate at physiological plasma concentration
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Authors: Rochefort, H., & Garcia, M.
Affiliations: Inserm (FR)
ORCID: Garcia, Marcel
Venue: Pharmacology & Therapeutics
Publisher: Elsevier BV
Published: 1983-01
Volume: 23
Issue: 2
Pages: 193-216
ISSN: 0163-7258 (ISSN-L)
DOI: 10.1016/0163-7258(83)90013-x
OpenAlex: W2023676722
Cited by: 107
References: 129
Citations by year: 2026: 2 · 2025: 2 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 4 · 2013: 1 · 2012: 1
FWCI: 2.62
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Pharmacology & Therapeutics (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Male Breast Health Studies
Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
Keywords: androgens, estrogenic activity, antiestrogenic activity, gynecomastia, male breast enlargement, breast histopathology
MeSH terms: Androgens, Animals, Breast Neoplasms, Cell Nucleus, Estrogen Antagonists, Estrogens, Female, Humans, Neoplasms, Receptors, Estrogen, Receptors, Progesterone, Rats

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