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 Siu T. 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… 

A physiologic role for testosterone in limiting estrogenic stimulation of the breast

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.

Co-expression of estrogen receptor-alpha and targets of estrogen receptor action in proliferating monkey mammary epithelial cells

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.

Primate Mammary Gland Insulin-Like Growth Factor System

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.

Differential regulation of Estrogen Receptor (ER)α and ERβ in primate mammary gland

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.

Differential effects of exogenous androgen and an androgen receptor antagonist in the peri- and postpubertal murine mammary gland.

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.

Mammary gland and endometrial effects of testosterone in combination with oral estradiol and progesterone

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.

Androgens inhibit the stimulatory action of 17β-estradiol on normal human breast tissue in explant cultures.

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.

Androgen receptor inactivation resulted in acceleration in pubertal mammary gland growth, upregulation of ERα expression, and Wnt/β-catenin signaling in female mice.

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.

Immunocytochemical Localization of Sex Steroid Hormone Receptors in Normal Human Mammary Gland

  • Sijie LiB. Han G. Pelletier
  • Medicine, Biology
    The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society
  • 2010
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.

AIB1 sequestration by androgen receptor inhibits estrogen-dependent cyclin D1 expression in breast cancer cells

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.
...

References

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