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Site-specific regulation of oestrogen receptor-α and -β by oestradiol in human adipose tissue
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Anwar, A., McTernan, P. G. (Philip G.), Anderson, L. A., Askaa, J., Moody, C. G., Barnett, A. H., Eggo, M. C. and Kumar, Sudhesh (2001) Site-specific regulation of oestrogen receptor-α and -β by oestradiol in human adipose tissue. Diabetes, Obesity and Metabolism, Volume 3 (Number 5). pp. 338-349. doi:10.1046/j.1463-1326.2001.00145.x ISSN 1462-8902.
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Official URL: http://dx.doi.org/10.1046/j.1463-1326.2001.00145.x
Abstract
Aim To examine the expression of oestrogen receptors α and β (ERα and ERβ) and their regulation by 17β-oestradiol (E2) in stromal cells and adipocytes from human subcutaneous (s.c.) and omental (o.m.) adipose tissue.
Methods Subcutaneous and o.m. abdominal adipose tissues were obtained from 10 women (mean age 63.5 ± 4.8 years; mean weight 75.6 ± 6.7 kg) undergoing elective or cosmetic surgery. Immunohistochemistry and RT-PCR analysis were used to detect the presence of ERα and ERβ. The regulation of ERα and ERβ by E2 (10−7 M to 10−9 M) was examined using Western immunoblotting analysis in both s.c. and o.m. stromal cells and mature adipocytes cultured in serum-free, phenol red-free medium.
Results Immunostaining of s.c. and o.m. adipose tissue showed that the ER subtypes were localized predominantly within the nucleus. Western analysis demonstrated that E2 treatments differentially altered ERα and ERβ expression in s.c. and o.m. adipocytes. In s.c. and o.m. stromal cells, E2 (10−8 M) produced a significant up regulation relative to control of 66 kDa ERα (s.c.:1.87 ± 0.22; o.m.:1.97 ± 0.17; p < 0.05) and 60 kDa ERβ (s.c.:1.66 ± 0.3; o.m.: 1.68 ± 0.16; p < 0.05). In s.c. adipocytes, however, ERα expression significantly decreased with E2 10−8 M relative to control while ERβ expression increased (ERα 0.58 ± 0.06, ERβ: 1.47 ± 0.11; p < 0.05). In o.m. adipocytes, the inhibition of ERα with E2 was not observed (ERα 1.86 ± 0.36, ERβ:1.03 ± 0.15, p < 0.05)
Conclusions ERα and ERβ are expressed but differentially regulated by E2 in s.c. and o.m. adipocytes and stromal cells. The upregulation of ERβ by E2 suggests that E2 maintains the expression of these receptors. The feed-back inhibition of ERα expression by E2 in s.c. but not o.m. adipocytes observed in vitro is consistent with the data from ERα knock out mice where s.c. fat is increased. Selective ER modulators may have different effects in different adipose sites.
Item Type: | Journal Article | ||||
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||
Journal or Publication Title: | Diabetes, Obesity and Metabolism | ||||
Publisher: | Blackwell | ||||
ISSN: | 1462-8902 | ||||
Official Date: | 2001 | ||||
Dates: |
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Volume: | Volume 3 | ||||
Number: | Number 5 | ||||
Page Range: | pp. 338-349 | ||||
DOI: | 10.1046/j.1463-1326.2001.00145.x | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access |
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