Androgens Inhibit the Stimulatory Action of 17β-Estradiol on Normal Human Breast Tissue in Explant Cultures.
(2012) In Journal of Clinical Endocrinology and Metabolism 97(7). p.1116-1127- Abstract
- Background: The data concerning the effects and safety of androgen in human breast tissue are conflicting.
Objective: Our aim was to analyze the effects of androgens on normal human breast tissue (HBT).
Approach: We cultured explants of HBT (obtained from reduction mammoplasty operations of postmenopausal women) with or without testosterone (T) and 5α-dihydrotestosterone (DHT) or in combination with 17β-estradiol (E(2)) for 7 and 14 d to study the effects of androgens on proliferation, apoptosis, target gene expression, and steroid receptors. The androgen receptor (AR) and estrogen receptor (ER) dependences of the effects were studied with the antihormones bicalutamide and fulvestrant,... (More) - Background: The data concerning the effects and safety of androgen in human breast tissue are conflicting.
Objective: Our aim was to analyze the effects of androgens on normal human breast tissue (HBT).
Approach: We cultured explants of HBT (obtained from reduction mammoplasty operations of postmenopausal women) with or without testosterone (T) and 5α-dihydrotestosterone (DHT) or in combination with 17β-estradiol (E(2)) for 7 and 14 d to study the effects of androgens on proliferation, apoptosis, target gene expression, and steroid receptors. The androgen receptor (AR) and estrogen receptor (ER) dependences of the effects were studied with the antihormones bicalutamide and fulvestrant, respectively.Results:The hormone responsiveness of cultured breast tissue was assessed by assaying apolipoprotein-D and prostate-specific antigen expression increased by androgens and amphiregulin and trefoil factor-1 expression induced by E(2) treatment. T and DHT reduced proliferation and increased apoptosis in breast epithelium, the effects of which were reversed by bicalutamide. In combination with E(2), they suppressed E(2)-stimulated proliferation and cell survival. DHT also inhibited basal (P < 0.05) and E(2)-induced expression of cyclin-D1 mRNA (P < 0.05). Immunohistochemistry showed that T (P < 0.05) and DHT (P < 0.05) increased the relative number of AR-positive cells, whereas ERα-positive (P < 0.001) cell numbers were strongly decreased. The percentage of ERβ-positive cells remained unchanged. E(2) treatment increased ERα-positive (P < 0.01) cells, whereas AR- (P < 0.05) and ERβ-expressing (P < 0.001) cells diminished. These effects were repressed in combination cultures of E(2) with T and DHT.
Conclusion: 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. These effects were associated with changes in the proportions of ERα- and AR-positive epithelial cells. (Less)
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https://lup.lub.lu.se/record/2519009
- author
- Eigeliene, Natalija ; Elo, Teresa ; Linhala, Mari ; Hurme, Saija ; Erkkola, Risto and Härkönen, Pirkko LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Clinical Endocrinology and Metabolism
- volume
- 97
- issue
- 7
- pages
- 1116 - 1127
- publisher
- Oxford University Press
- external identifiers
-
- wos:000306286100005
- pmid:22535971
- scopus:84863597131
- pmid:22535971
- ISSN
- 1945-7197
- DOI
- 10.1210/jc.2011-3228
- language
- English
- LU publication?
- yes
- additional info
- Department affilation moved from v1000588 (Tumour Biology, Malmö) to v1000562 (Department of Translational Medicine) on 2016-01-18 14:39:30.
- id
- 507a9d12-2050-4ec0-9cea-4c4a6093a25c (old id 2519009)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22535971?dopt=Abstract
- date added to LUP
- 2016-04-01 14:22:18
- date last changed
- 2022-03-14 05:31:15
@article{507a9d12-2050-4ec0-9cea-4c4a6093a25c,
abstract = {{Background: The data concerning the effects and safety of androgen in human breast tissue are conflicting.<br/><br>
<br/><br>
Objective: Our aim was to analyze the effects of androgens on normal human breast tissue (HBT).<br/><br>
<br/><br>
Approach: We cultured explants of HBT (obtained from reduction mammoplasty operations of postmenopausal women) with or without testosterone (T) and 5α-dihydrotestosterone (DHT) or in combination with 17β-estradiol (E(2)) for 7 and 14 d to study the effects of androgens on proliferation, apoptosis, target gene expression, and steroid receptors. The androgen receptor (AR) and estrogen receptor (ER) dependences of the effects were studied with the antihormones bicalutamide and fulvestrant, respectively.Results:The hormone responsiveness of cultured breast tissue was assessed by assaying apolipoprotein-D and prostate-specific antigen expression increased by androgens and amphiregulin and trefoil factor-1 expression induced by E(2) treatment. T and DHT reduced proliferation and increased apoptosis in breast epithelium, the effects of which were reversed by bicalutamide. In combination with E(2), they suppressed E(2)-stimulated proliferation and cell survival. DHT also inhibited basal (P < 0.05) and E(2)-induced expression of cyclin-D1 mRNA (P < 0.05). Immunohistochemistry showed that T (P < 0.05) and DHT (P < 0.05) increased the relative number of AR-positive cells, whereas ERα-positive (P < 0.001) cell numbers were strongly decreased. The percentage of ERβ-positive cells remained unchanged. E(2) treatment increased ERα-positive (P < 0.01) cells, whereas AR- (P < 0.05) and ERβ-expressing (P < 0.001) cells diminished. These effects were repressed in combination cultures of E(2) with T and DHT.<br/><br>
<br/><br>
Conclusion: 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. These effects were associated with changes in the proportions of ERα- and AR-positive epithelial cells.}},
author = {{Eigeliene, Natalija and Elo, Teresa and Linhala, Mari and Hurme, Saija and Erkkola, Risto and Härkönen, Pirkko}},
issn = {{1945-7197}},
language = {{eng}},
number = {{7}},
pages = {{1116--1127}},
publisher = {{Oxford University Press}},
series = {{Journal of Clinical Endocrinology and Metabolism}},
title = {{Androgens Inhibit the Stimulatory Action of 17β-Estradiol on Normal Human Breast Tissue in Explant Cultures.}},
url = {{https://lup.lub.lu.se/search/files/3937359/2545215.pdf}},
doi = {{10.1210/jc.2011-3228}},
volume = {{97}},
year = {{2012}},
}