| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Developmental Endocrinology Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA
1Correspondence: NICHD, NIH, Bldg. 10, Rm. 10N262, Bethesda, MD 20892, USA. E-mail: bondyc{at}exchange.nih.gov
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,
17ß 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 (ER
) mRNA expression by 50% (P<0.0001;
ERß mRNA was not detected in the primate mammary gland). Progesterone
did not alter E2’s proliferative effects, but testosterone reduced
E2-induced proliferation by 40% (P<0.002) and
entirely abolished E2-induced augmentation of ER expression.
Tamoxifen had a significant agonist effect in the ovariectomized
monkey, producing a threefold increase in mammary epithelial
proliferation (P<0.01), but tamoxifen also reduced
ER expression below placebo level. Androgen receptor (AR) mRNA was
detected in mammary epithelium by in situ hybridization.
AR mRNA levels were not altered by E2 alone but were significantly
reduced by E2/T and tamoxifen treatment. Because combined E2/T and
tamoxifen had similar effects on mammary epithelium, we investigated
the regulation of known sex steroid-responsive mRNAs in the primate
mammary epithelium. E2 alone had no effect on apolipoprotein D (ApoD)
or IGF binding protein 5 (IGFBP5) expression, but E2/T and tamoxifen
treatment groups both demonstrated identical alterations in these mRNAs
(ApoD was decreased and IGFBP5 was increased). These observations
showing androgen-induced down-regulation of mammary epithelial
proliferation and ER expression suggest that combined estrogen/androgen
hormone replacement therapy might reduce the risk of breast cancer
associated with estrogen replacement. In addition, these novel findings
on tamoxifen’s androgen-like effects on primate mammary epithelial sex
steroid receptor expression suggest that tamoxifen’s protective action
on mammary gland may involve androgenic effects.—Zhou, J., Ng, S.,
Adesanya-Famuiya, O., Anderson, K., Bondy, C. A. Testosterone
inhibits estrogen-induced mammary epithelial proliferation and
suppresses estrogen receptor expression.
Key Words: breast cancer • androgen • tamoxifen • monkey
This article has been cited by other articles:
|
|
 |
|
  S. N. Birrell, L. M. Butler, J. M. Harris, G. Buchanan, and W. D. Tilley Disruption of androgen receptor signaling by synthetic progestins may increase risk of developing breast cancer FASEB J, August 1, 2007; 21(10): 2285 - 2293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Wierman, R. Basson, S. R. Davis, S. Khosla, K. K. Miller, W. Rosner, and N. Santoro Androgen Therapy in Women: An Endocrine Society Clinical Practice Guideline J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 3697 - 3710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Perez-Palacios, R. Santillan, R. Garcia-Becerra, E. Borja-Cacho, F. Larrea, P. Damian-Matsumura, L. Gonzalez, and A. E Lemus Enhanced formation of non-phenolic androgen metabolites with intrinsic oestrogen-like gene transactivation potency in human breast cancer cells: a distinctive metabolic pattern. J. Endocrinol., September 1, 2006; 190(3): 805 - 818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Anguiano, A. Lopez, G. Delgado, C. Romero, and C. Aceves Deiodinase type 1 activity is expressed in the prostate of pubescent rats and is modulated by thyroid hormones, prolactin and sex hormones. J. Endocrinol., August 1, 2006; 190(2): 363 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Slagter, L. J.G. Gooren, A. Scorilas, C. D. Petraki, and E. P. Diamandis Effects of Long-term Androgen Administration on Breast Tissue of Female-to-Male Transsexuals J. Histochem. Cytochem., August 1, 2006; 54(8): 905 - 910. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Tamimi, S. E. Hankinson, W. Y. Chen, B. Rosner, and G. A. Colditz Combined Estrogen and Testosterone Use and Risk of Breast Cancer in Postmenopausal Women Arch Intern Med, July 24, 2006; 166(14): 1483 - 1489. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F Labrie Future perspectives of selective estrogen receptor modulators used alone and in combination with DHEA. Endocr. Relat. Cancer, June 1, 2006; 13(2): 335 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L A Nolan and A Levy The effects of testosterone and oestrogen on gonadectomised and intact male rat anterior pituitary mitotic and apoptotic activity. J. Endocrinol., March 1, 2006; 188(3): 387 - 396. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Lovering and W. A. Romani Effect of testosterone on the female anterior cruciate ligament Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2005; 289(1): R15 - R22. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Veldhuis, J. N. Roemmich, E. J. Richmond, A. D. Rogol, J. C. Lovejoy, M. Sheffield-Moore, N. Mauras, and C. Y. Bowers Endocrine Control of Body Composition in Infancy, Childhood, and Puberty Endocr. Rev., February 1, 2005; 26(1): 114 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Cheng, Y. Li, Y. Omoto, Y. Wang, T. Berg, M. Nord, P. Vihko, M. Warner, Y.-S. Piao, and J.-A. Gustafsson Differential Regulation of Estrogen Receptor (ER){alpha} and ER{beta} in Primate Mammary Gland J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 435 - 444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.M. Rivera-Woll, M. Papalia, S.R. Davis, and H.G. Burger Androgen insufficiency in women: diagnostic and therapeutic implications Hum. Reprod. Update, September 1, 2004; 10(5): 421 - 432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Somboonporn and S. R. Davis Testosterone Effects on the Breast: Implications for Testosterone Therapy for Women Endocr. Rev., June 1, 2004; 25(3): 374 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Cardenas and W. F. Pope Attenuation of Estrogenic Effects by Dihydrotestosterone in the Pig Uterus Is Associated with Downregulation of the Estrogen Receptors Biol Reprod, February 1, 2004; 70(2): 297 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Rivas, C. Mckinnell, J. S. Fisher, N. Atanassova, K. Williams, and R. M. Sharpe Neonatal Coadministration of Testosterone With Diethylstilbestrol Prevents Diethylstilbestrol Induction of Most Reproductive Tract Abnormalities in Male Rats J Androl, July 1, 2003; 24(4): 557 - 567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Shin and I. M. Verma BRCA2 cooperates with histone acetyltransferases in androgen receptor-mediated transcription PNAS, June 10, 2003; 100(12): 7201 - 7206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Morley and H. M. Perry III Androgens and Women at the Menopause and Beyond J. Gerontol. A Biol. Sci. Med. Sci., May 1, 2003; 58(5): M409 - 416. [Full Text] [PDF]
|
|
|
|
|
|
F. Labrie, V. Luu-The, C. Labrie, A. Belanger, J. Simard, S.-X. Lin, and G. Pelletier Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone Endocr. Rev., April 1, 2003; 24(2): 152 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Rivas, J. S. Fisher, C. McKinnell, N. Atanassova, and R. M. Sharpe Induction of Reproductive Tract Developmental Abnormalities in the Male Rat by Lowering Androgen Production or Action in Combination with a Low Dose of Diethylstilbestrol: Evidence for Importance of the Androgen-Estrogen Balance Endocrinology, December 1, 2002; 143(12): 4797 - 4808. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
