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

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.

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.

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.

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.

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.

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.

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.

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.

Hormonal effects on the mammary gland of postmenopausal nonhuman primates.

TLDR
Macaques are Old World anthropoid primates with a high degree of genetic identity to human beings and striking similarities in breast development, reproductive endocrinology, and menstrual cycle characteristics, which lend support to a biomarker approach for modeling breast cancer risk.

Testosterone effects on the breast: implications for testosterone therapy for women.

TLDR
Exogenous testosterone may serve as a natural endogenous protector of the breast and limit mitogenic and cancer-promoting effects of estrogen on mammary epithelium, and inclusion of testosterone in postmenopausal estrogen-progestin regimens has the potential to ameliorate the stimulating effects of combined estrogen- Progestin on the breast.
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