Testosterone inhibits estrogen‐induced mammary epithelial proliferation and suppresses estrogen receptor expression

@article{Zhou2000TestosteroneIE,
  title={Testosterone inhibits estrogen‐induced mammary epithelial proliferation and suppresses estrogen receptor expression},
  author={J Zhou and S Ng and O Adesanya-Famuiya and K. Anderson and Carolyn A. Bondy},
  journal={The FASEB Journal},
  year={2000},
  volume={14},
  pages={1725 - 1730}
}
This study investigated the effect of sex steroids and tamoxifen on primate mammary epithelial proliferation and steroid receptor gene expression. Ovariectomized rhesus monkeys were treated with placebo, 17β estradiol (E2) alone or in combination with progesterone (E2/P) or testosterone (E2/T), or tamoxifen for 3 days. E2 alone increased mammary epithelial proliferation by ~sixfold (P<0.0001) and increased mammary epithelial estrogen receptor (ERα) mRNA expression by ~50% (P<0.0001; ERβ mRNA… Expand
View on Wiley
zenodo.org
188 Citations
Highly Influential Citations
6
Background Citations
74
Methods Citations
1
Results Citations
9

188 Citations

Citation Type

Citation Type

A physiologic role for testosterone in limiting estrogenic stimulation of the breast
TLDR
Treatment with a balanced formulation including all ovarian hormones may prevent or reduce estrogenic cancer risk in the treatment of girls and women with ovarian failure and menopause. Expand
Co-expression of estrogen receptor-alpha and targets of estrogen receptor action in proliferating monkey mammary epithelial cells
TLDR
ERα is expressed in proliferating mammary epithelial cells together with the estrogen-induced proteins MYC, cyclin D1 and SDF-1, consistent with a direct mitogenic action by estrogen in primate mammary peptide epithelium. Expand
Primate Mammary Gland Insulin-Like Growth Factor System
TLDR
E2-induced proliferation is associated with upregulation of both IGF1 and IGF2 expression and downregulation of BP2 expression, which suggests that the local mammary IGF system is involved in sex steroid-induced mammary epithelial cell hyperplasia. Expand
Differential regulation of Estrogen Receptor (ER)α and ERβ in primate mammary gland
TLDR
Control of gonadal hormone receptors during the menstrual cycle, pregnancy, and lactation in rhesus monkey mammary gland is reported on and it is found that ERα but not ERβ is down-regulated when E2 levels increase and when cells enter the cell cycle. Expand
Differential effects of exogenous androgen and an androgen receptor antagonist in the peri- and postpubertal murine mammary gland.
TLDR
The findings indicate that androgen signaling influences development and structure of the adult mammary gland and that homeostasis between estrogen and androgens signaling in mature glands is critical to constrain the proliferative effects of estradiol. Expand
Mammary gland and endometrial effects of testosterone in combination with oral estradiol and progesterone
TLDR
The findings of this study do not support the idea that T antagonizes the effects of combined hormone therapy on breast proliferation or markers of estrogen-receptor activity. Expand
Androgens inhibit the stimulatory action of 17β-estradiol on normal human breast tissue in explant cultures.
TLDR
T and DHT inhibited proliferation and increased apoptosis in the epithelium of cultured normal HBT and opposed E(2)-stimulated proliferation and cell survival in an AR-dependent manner and were associated with changes in the proportions of ERα- and AR-positive epithelial cells. Expand
Androgen receptor inactivation resulted in acceleration in pubertal mammary gland growth, upregulation of ERα expression, and Wnt/β-catenin signaling in female mice.
TLDR
An inhibitory role of AR-mediated androgen actions in pubertal mammary gland development is revealed by reducing epithelial cell proliferation and could be mediated by regulation of Wnt/β-catenin signaling. Expand
Immunocytochemical Localization of Sex Steroid Hormone Receptors in Normal Human Mammary Gland
  • Sijie Li, B. Han, +4 authors G. Pelletier
  • Chemistry, Medicine
  • The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society
  • 2010
TLDR
All sex steroids can directly act on epithelial cells to modulate development and function of the human mammary gland, and estrogens and androgens can also indirectly influence epithelial cell activity by an action on stromal cells. Expand
AIB1 sequestration by androgen receptor inhibits estrogen-dependent cyclin D1 expression in breast cancer cells
TLDR
The hypothesis that AIB1 sequestration by AR may be an effective mechanism to explain the reduction of estrogen-induced cyclin D1 gene activity in estrogen-dependent breast cancer cells is supported. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 36 REFERENCES
Primate Mammary Gland Insulin-Like Growth Factor System
TLDR
E2-induced proliferation is associated with upregulation of both IGF1 and IGF2 expression and downregulation of BP2 expression, which suggests that the local mammary IGF system is involved in sex steroid-induced mammary epithelial cell hyperplasia. Expand
Roles of Estrogen and Progesterone in Normal Mammary Gland Development Insights from Progesterone Receptor Null Mutant Mice and In Situ Localization of Receptor
  • G. Shyamala
  • Medicine, Biology
  • Trends in Endocrinology & Metabolism
  • 1997
TLDR
The general features and the effects of estrogen and progesterone on normal mammary gland development are reviewed, followed by a discussion of the authors' recent studies, which emphasize the primary importance of progester one and progestersone receptor for the normal Mammary epithelial cell proliferation and differentiation. Expand
Variation of estrogen and progesterone receptor status in breast cancer after tamoxifen therapy.
TLDR
It can be concluded that tamoxifen reduced significantly the ER concentration while no changes were observed in PR values, and the variation in steroid receptor content under tamoxIFen therapy may also contribute to the evaluation of the hormone dependency of gynecologic malignancies. Expand
Androgen receptor gene expression in the primate ovary: cellular localization, regulation, and functional correlations.
TLDR
The positive correlation between granulosa AR gene expression and cell proliferation and negative correlation with programmed cell death suggests that androgens stimulate early primate follicle development. Expand
Additive stimulatory action of glucocorticoids and androgens on basal and estrogen-repressed apolipoprotein-D messenger ribonucleic acid levels and secretion in human breast cancer cells.
TLDR
The effects of steroids on apo-D gene expression, intracellular apo -D protein content, and secretion are opposite their respective specific effects on cell proliferation in human ZR-75-1 breast cancer cells. Expand
Tamoxifen exerts testosterone-dependent and independent effects on thymic involution.
TLDR
Findings show that tamoxifen is able to reverse ageing changes in the thymus by suppressing testosterone production, while conversely, exerts thymolytic effects in the absence of androgens. Expand
Androgens stimulate early stages of follicular growth in the primate ovary.
TLDR
Findings show that, over the short term at least, androgens are not atretogenic and actually enhance follicular growth and survival in the primate, providing a plausible explanation for the pathogenesis of "polycystic" ovaries in hyperandrogenism. Expand
The role of oestrogens and progestagens in the epidemiology and prevention of breast cancer.
  • T. Key, M. Pike
  • Medicine
  • European journal of cancer & clinical oncology
  • 1988
TLDR
Both hypotheses suggest that the risk of breast cancer could be reduced by delaying the onset of regular ovulatory menstrual cycles and by minimizing the therapeutic use of oestrogens, and possibly of progestagens, in postmenopausal women. Expand
Additive inhibitory effects of an androgen and the antiestrogen EM-170 on estradiol-stimulated growth of human ZR-75-1 breast tumors in athymic mice.
TLDR
The present data show that the androgen DHT as well as medroxy-progesterone acetate are potent inhibitors of E2-stimulated human ZR-75-1 breast cancer cell growth in vivo, suggesting the interest of combining these 2 classes of compounds acting, at least partially, through different mechanisms, in order to improve breast cancer therapy in women. Expand
Differential effects of estrogen-androgen and estrogen-only therapy on vasomotor symptoms, gonadotropin secretion, and endogenous androgen bioavailability in postmenopausal women.
TLDR
The greater efficacy of combination therapy on somatic symptoms could be mediated by the same mechanism responsible for the suppressive effects of estrogen-androgen therapy on luteinizing hormone secretion. Expand
...
1
2
3
4
...