Oestrogen receptor beta mediates decreased occlusal loading induced inhibition of chondrocyte maturation in female mice

Abstract Introduction Oestrogen receptor beta (ER-β) is abundantly expressed in breast cancer (BC), but its impact on neoadjuvant chemotherapy outcome is unknown. Patients and Methods Patients treated in the neoadjuvant GeparTrio trial with available tissue for immunohistochemical analyses were included. Nuclear ER-β expression was correlated with clinico-pathologic characteristics. The impact of its expression on pathological complete response (pCR [ypT0/ypN0]) and survival was determined. Results Samples of 570 patients were available. Low nuclear ER-β expression (IRS < 9) was observed in 48.4% of hormone receptor positive and 58.6% of hormone receptor negative tumours. Low nuclear ER-β expression was associated with higher pCR rates compared to high nuclear ER-β expression (16.1% vs. 4.7%, p = 0.026). Low ER-β expression was no independent predictor of pCR in multivariate analyses. Disease-free and overall survival were not statistically different between patients with high and low nuclear ER-β expression. Triple-negative BCs showed low nuclear ER-β expression in 57.7%, and pCR rates were 27.1% and 0% (p = 0.23) in low and high ER-β expressing tumours, respectively. Conclusion Low ER-β expression is associated with improved pCR rates in univariate analyses. However multivariate analyses and survival analyses do not indicate an impact of ER-β on survival in patients undergoing neoadjuvant chemotherapy. Further examination of ER-β as predictor for endocrine therapy might be of value.

Download Full-text

Detection of oestrogenic activity of steroids present during mammalian gestation using oestrogen receptor alpha- and oestrogen receptor beta-specific in vitro assays

Journal of Endocrinology ◽

10.1677/joe.0.1740435 ◽

2002 ◽

Vol 174 (3) ◽

pp. 435-446 ◽

Cited By ~ 18

Author(s):

JG Lemmen ◽

CE van den Brink ◽

J Legler ◽

PT van der Saag ◽

B van der Burg

Keyword(s):

Steroid Hormones ◽

Oestrogen Receptor ◽

In Vitro Assays ◽

Relative Preference ◽

Oestrogen Receptor Alpha ◽

Total Pool ◽

Er Alpha ◽

Receptor Beta

Numerous steroid hormones are present in the foetus but their potential to activate oestrogen receptor (ER) alpha and/or beta is largely unknown. In this study, in vitro assays were developed to rapidly and specifically detect ERalpha or ERbeta activation by these steroid hormones. Our results showed that several oestrogen precursors and androgens are able to activate both ERalpha and ERbeta. Of special interest is that some of these precursors are able to activate ERalpha and ERbeta at concentrations that are present during human gestation. Moreover, some precursors (dehydroepiandrosterone (DHEA) and 17-hydroxylated pregnenolone sulphate) and androgens (5-androsten-3beta,16alpha,17beta-triol and testosterone) showed a more than 100-fold relative preference for ERbeta transactivation over ERalpha transactivation when compared with 17beta-oestradiol. Due to their relatively high levels, the precursor steroids DHEA and pregnenolone may be of particular importance in the regulation of ERbeta activity in vivo. To obtain information about the oestrogenic activity of the total pool of steroid hormones present during mammalian gestation, steroids were extracted from mouse embryos at different prenatal stages and assayed for oestrogenic activity in the established in vitro assays. Oestrogenic activity was detected in steroid extracts from all stages tested. This study has demonstrated that oestrogen receptor agonists are present in the murine embryo and that oestrogen precursors may contribute to the total pool of agonists during foetal life.

Download Full-text

Dominant expression and distribution of oestrogen receptor beta over oestrogen receptor alpha in the human corpus luteum

MHR Basic science of reproductive medicine ◽

10.1093/molehr/7.2.137 ◽

2001 ◽

Vol 7 (2) ◽

pp. 137-145 ◽

Cited By ~ 16

Author(s):

K. Hosokawa

Keyword(s):

Corpus Luteum ◽

Oestrogen Receptor ◽

Receptor Alpha ◽

Oestrogen Receptor Alpha ◽

Human Corpus Luteum ◽

Receptor Beta

Download Full-text

248. Oestrogen receptor beta is involved in the regulation of Leydig cell number in the mouse

Reproduction Fertility and Development ◽

10.1071/srb05abs248 ◽

2005 ◽

Vol 17 (9) ◽

pp. 99

Author(s):

M. Gould ◽

H. D. Nicholson

Keyword(s):

Leydig Cell ◽

Sertoli Cells ◽

Leydig Cells ◽

Oestrogen Receptor ◽

Physiological Role ◽

Plasma Testosterone ◽

Testis Weight ◽

Wild Type ◽

Significant Difference ◽

Receptor Beta

Recent evidence suggests that oestrogen plays a physiological role in the testis. Both oestrogen receptor alpha and oestrogen receptor beta (ERb) are present in the testis and administration of oestrogen has been shown to inhibit the development of Sertoli, Leydig and germ cells. This study investigates the effect of ERb on the testis using ERb knockout mice (bERKO). Adult male bERKO mice (n=8) and their wild-type littermates (n=7) were killed at 11 weeks postpartum. One testis from each animal was fixed in Bouin’s fluid and embedded. Each testis was fractionated and thick sections cut and stained with PAS. The optical disector method was used to count the number of Leydig cells, Sertoli cells, spermatogonia, spermatocytes and spermatids in each testis. Trunk blood was collected and plasma testosterone concentrations measured by radioimmunoassay. No significant differences in body or testis weight were seen between the bERKO or wild-type mice. Similar numbers of Sertoli cells, spermatogonia, spermatocytes and spermatids were also observed between the two groups. The number of Leydig cells was significantly increased in bERKO mice compared with their wild-type littermates (P < 0.05). Despite the increased number of Leydig cells in the bERKO mice there was no significant difference in plasma testosterone concentrations in this group compared to the wild-type mice. Oestrogen has been reported to inhibit proliferation of adult-type Leydig cells and to inhibit steroidogenesis. This study suggests that the regulation of Leydig cell proliferation may be mediated by ERb. The presence of normal circulating testosterone concentrations in bERKO mice suggests that the effects of oestrogen on steroidogenesis are not brought about by ERbeta.

Download Full-text