Site-specific regulation of oestrogen receptor-α and -β by oestradiol in human adipose tissue

Authors: Anwar, A.1; McTernan, P. G.1; Anderson, L. A.1; Askaa, J.2; Moody, C. G.1; Barnett, A. H.1; Eggo, M. C.1; Kumar, S.1

Source: Diabetes, Obesity and Metabolism, Volume 3, Number 5, October 2001 , pp. 338-349(12)

Publisher: Wiley-Blackwell

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Abstract:

SUMMARY 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.

Keywords: oestrogen receptors; human adipose tissue

Document Type: Research article

Affiliations: 1: Department of Medicine, University of Birmingham, Queen Elizabeth Hospital and Birmingham Heartlands Hospital, Birmingham, UK 2: DAKO A/S, 2600 Glostrup, Denmark

Publication date: 2001-10-01

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