Estrogen receptor beta - a novel receptor opens up new possibilities for cancer diagnosis and treatment

Enmark, Eva; Gustafsson, Jan‐Åke

doi:10.1677/erc.0.0050213

Cited by 22 publications

(20 citation statements)

References 49 publications

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“…Expression of sex steroid hormone receptors examined in this study has been reported in various normal human organs [27][28][29][30][31][32]. In the skin, Thornton et al demonstrated the presence of these receptors in scalp skin [23].…”

Section: Discussionsupporting

confidence: 63%

Sex Steroid Hormone Receptors in Human Skin Appendage and its Neoplasms

et al. 2005

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Abstract. Sex steroids have been postulated to influence pathophysiology of human skin through various skin appendages. The presence of sex steroid receptors has been also reported in adnexal tumors but its details still remained unknown. Therefore, in this study, we immunolocalized sex steroid receptor protein (estrogen receptor (ER)a, ERb, progesterone receptor (PR)A, PRB and androgen receptor (AR)) in 23 cases of non-pathological skin (male: 10, female: 13) and in 50 cases of skin adnexal tumors (male 24, female 26; 38 benign and 12 malignant). ERa immunoreactivity was detected exclusively in basal cells of sebaceous glands of non-pathological skin. AR and PRB immunoreactivity was detected in both differentiated and basal cells of sebaceous gland. AR and ERb immunoreactivity was also detected in sebaceous and eccrine sweat glands but not in outer root sheath of hair follicles. In sebaceous gland neoplasms, the number of ERa positive cases was significantly lower in skin appendage neoplasms than non-pathological skin. ERb immunoreactivity was not detected in any of sebaceous gland neoplasms examined. There were no significant differences in PRA, PRB and AR immunoreactivity between non-pathological sebaceous gland and its neoplasm. In sweat gland neoplasms, the number of AR positive cases was significantly lower in benign neoplasms than their non-pathological counterpart. Therefore sex steroids are considered to play important roles in regulation of non-pathological skin appendage function and pathogenesis and/or development of its neoplasm. In addition, the status of the great majority of sex steroid hormone receptors was maintained throughout the process of neoplastic transformation of skin appendages, except for AR and ERa in sweat and sebaceous gland neoplasms.

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Section: Discussionsupporting

confidence: 63%

Sex Steroid Hormone Receptors in Human Skin Appendage and its Neoplasms

et al. 2005

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“…For example, most autoimmune diseases are more common in women than in men and quite frequently begin under conditions when estrogen levels change dramatically, e. g., during puberty, menopause, or pregnancy [138,139]. The exact mechanisms involved in these metabolic processes have yet to be determined.…”

Section: S Other Diseasesmentioning

confidence: 99%

Isoflavones, substances with multi-biological and clinical properties

Ren¹,

Kuhn²,

Wegner³

et al. 2001

Eur J Nutr

123

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Isoflavones, rich in soybean, are currently receiving much attention because of their potential role in preventing and treating cancer and other human chronic diseases. The present review provides an overview of the recent results in this research field. Data from epidemiological reports and laboratories have shown that isoflavones have multi-biological and pharmacological effects in animals and humans. These include estrogenic and antiestrogenic effects, cell signalling conduction, as well as cell growth and death. Based on these properties, soy protein and isoflavones have been associated with reduced incidences of breast and prostate cancers, cardiovascular diseases or osteoporosis, and exhibit some other favorable effects. The mechanism through which isoflavones may exert the above-mentioned functions are not only based on the estrogenic properties of isoflavones, but also on their role as protein tyrosine kinase inhibitors, as regulators of gene transcription, modulators of transcription factors, antioxidants, as well as by altering some enzyme activities. However, to draw a clear conclusion regarding the clinical use of isoflavones further investigation would be required, although only a few effects of short- or long-term use of soy proteins are known in humans.

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“…Results of recent studies have demonstrated that ERs are widely expressed in a variety of tissues. In addition to those tissues described above, ERs have been shown to be expressed in the mammary gland, lung, and intestine (1,2). Estrogen is able to enter the fetal circulation via the umbilical vein (3), whereby it binds to ER, which has also been reported in various human fetal tissues (4,5).…”

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confidence: 99%

Systemic Distribution of Steroid Sulfatase and Estrogen Sulfotransferase in Human Adult and Fetal Tissues

Miki

Nakata

Suzuki

et al. 2002

The Journal of Clinical Endocrinology &Amp; Metabolism

154

125

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Estrogens play a key role in various target tissues. Enzymes involved in the biosynthesis and metabolism of these sex steroids also regulate estrogenic actions in these tissues. Estrone sulfate (E1S) is a major circulating plasma estrogen that is converted into the biologically active estrogen, estrone (E1), by steroid sulfatase (STS). E1 is also sulfated and reverted into E1S by estrogen sulfotransferase (EST). These two enzymes have recently been shown to play important roles in the in situ estrogen actions of various sex steroid-dependent human tumors. However, the distribution of STS and EST in normal adult and fetal human tissues remains largely unknown. Therefore, in this study, in addition to examining the tissue distribution of both STS and EST mRNA in human adult and fetal tissues using RT followed by quantitative PCR, we studied the activity of these enzymes using 3 H-labeled E1/E1S as substrates in the homogenates of various human adult tissues. We also examined the localization of STS and EST protein in human adult and fetal tissues using immunohistochemistry, and that of EST mRNA in the adult kidney using laser dissection microscopy and PCR. STS mRNA, enzyme activity, and immunoreactivity were either absent or detected at very low levels in all adult and fetal tissues examined in this study. EST mRNA expression, however, was detected in all of the tissues examined, except for adult spleen and pancreas. EST enzyme activities were consistent with those of mRNA expression in the great majority of the tissues examined. Marked EST immunoreactivity was detected in hepatocytes, adrenal gland (adult, zona fasciculate to the reticularis; fetus, fetal zone), and epithelial cells of the gastrointestinal tract, smooth muscle cells of the tunica media in aorta, Leydig cells of the testis, and syncytiotrophoblast of the placenta. Patterns of EST immunolocalization were similar between adult and fetal human tissues, but EST immunoreactivity was detected in the urinary tubules of adult kidney, whereas in the fetal kidney, it was localized in the interstitial cells surrounding the urinary tubules. In the adult kidney, the presence of EST mRNA was also confirmed in the cells of urinary tubules using laser dissection microscopy and RT-PCR.Although the number of human tissues available for examination in this study was limited, our results suggest that between the enzymes involved in estrogen activation or inactivation, EST and not STS is the more widely expressed enzyme in various peripheral tissues in humans. We speculate that EST may play an important role in protecting peripheral tissues from possible excessive estrogenic effects. (J Clin Endocrinol Metab 87: 5760 -5768, 2002)

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Estrogen receptor beta - a novel receptor opens up new possibilities for cancer diagnosis and treatment

Cited by 22 publications

References 49 publications

Sex Steroid Hormone Receptors in Human Skin Appendage and its Neoplasms

Sex Steroid Hormone Receptors in Human Skin Appendage and its Neoplasms

Isoflavones, substances with multi-biological and clinical properties

Systemic Distribution of Steroid Sulfatase and Estrogen Sulfotransferase in Human Adult and Fetal Tissues

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