scholarly journals Tumour nuclear oestrogen receptor beta 1 correlates inversely with parathyroid tumour weight

2015 ◽  
Vol 4 (1) ◽  
pp. 76-85 ◽  
Author(s):  
Felix Haglund ◽  
Gustaf Rosin ◽  
Inga-Lena Nilsson ◽  
C Christofer Juhlin ◽  
Ylva Pernow ◽  
...  

Primary hyperparathyroidism (PHPT) is a common endocrinopathy, frequently caused by a parathyroid adenoma, rarely by a parathyroid carcinoma that lacks effective oncological treatment. As the majority of cases are present in postmenopausal women, oestrogen signalling has been implicated in the tumourigenesis. Oestrogen receptor beta 1 (ERB1) and ERB2 have been recently identified in parathyroid adenomas, the former inducing genes coupled to tumour apoptosis. We applied immunohistochemistry and slide digitalisation to quantify nuclear ERB1 and ERB2 in 172 parathyroid adenomas, atypical adenomas and carcinomas, and ten normal parathyroid glands. All the normal parathyroid glands expressed ERB1 and ERB2. The majority of tumours expressed ERB1 (70.6%) at varying intensities, and ERB2 (96.5%) at strong intensities. Parathyroid carcinomas expressed ERB1 in three out of six cases and ERB2 in five out of six cases. The intensity of tumour nuclear ERB1 staining significantly correlated inversely with tumour weight (P=0.011), and patients whose tumours were classified as ERB1-negative had significantly greater tumour weight as well as higher serum calcium (P=0.002) and parathyroid hormone levels (P=0.003). Additionally, tumour nuclear ERB1 was not expressed differentially with respect to sex or age of the patient. Levels of tumour nuclear ERB2 did not correlate with clinical characteristics. In conclusion, decreased ERB1 immunoreactivity is associated with increased tumour weight in parathyroid adenomas. Given the previously reported correlation with tumour-suppressive signalling, selective oestrogen receptor modulation (SERMs) may play a role in the treatment of parathyroid carcinomas. Future studies of SERMs and oestrogen treatment in PHPT should consider tumour weight as a potential factor in pharmacological responsiveness.

2019 ◽  
Vol 79 (10) ◽  
pp. 1110-1117
Author(s):  
Florian Heitz ◽  
Sherko Kümmel ◽  
Bianca Lederer ◽  
Christine Solbach ◽  
Knut Engels ◽  
...  

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.


2002 ◽  
Vol 174 (3) ◽  
pp. 435-446 ◽  
Author(s):  
JG Lemmen ◽  
CE van den Brink ◽  
J Legler ◽  
PT van der Saag ◽  
B van der Burg

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.


2015 ◽  
Vol 60 (6) ◽  
pp. 818-824 ◽  
Author(s):  
Ilona Polur ◽  
Yosuke Kamiya ◽  
Manshan Xu ◽  
Bianca S. Cabri ◽  
Marwa Alshabeeb ◽  
...  

2005 ◽  
Vol 17 (9) ◽  
pp. 99
Author(s):  
M. Gould ◽  
H. D. Nicholson

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.


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