Estrogen biosynthesis in human liver - A comparison of aromatase activity for C-19 steroids in fetal liver, adult liver and hepatoma tissues of human subjects.

Yamamoto, Takatsugu; Sakai, C; Yamaki, Junko; K, Takamori; Yoshiji, Shuichi; Kitawaki, Jo; Fujii, Masahiro; Yasuda, Jinsuke; Honjo, Hideo; Okada, Hiroji

doi:10.1507/endocrj1954.31.277

Cited by 19 publications

(11 citation statements)

References 2 publications

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“…Although not frequently described, NET can be metabolized in humans to EE2 via hydroxylation of the A ring and a subsequent loss of H 2 O introducing aromaticity in the A ring. This effect was first described by Yamamoto et al [45,46], whereas Kuhl and Wiegratz recently discussed clinical implications of the formation of this potent estrogenic active metabolite in humans [47].…”

Section: Preparative Scale Biosynthesis and Nmr Analysismentioning

confidence: 88%

Determination and identification of estrogenic compounds generated with biosynthetic enzymes using hyphenated screening assays, high resolution mass spectrometry and off-line NMR

Vlieger

Kolkman

Ampt

et al. 2010

Journal of Chromatography B

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Section: Preparative Scale Biosynthesis and Nmr Analysismentioning

confidence: 88%

Determination and identification of estrogenic compounds generated with biosynthetic enzymes using hyphenated screening assays, high resolution mass spectrometry and off-line NMR

Vlieger

Kolkman

Ampt

et al. 2010

Journal of Chromatography B

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“…STS enzyme in the adult liver and adrenal gland demonstrated relatively high amounts of enzyme expression. Yamamoto et al (36) demonstrated that normal adult liver tissues had relatively high aromatase activity. Phornphutkul et al (37) reported relatively high aromatase activity and expression in an adrenal adenoma with very low activity and expression of aromatase in non-neoplastic adjacent adrenal.…”

Section: Discussionmentioning

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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“…In addition, the activation of ERα requires the binding to its natural ligand, 17β-estradiol, which was first reported in rat uteri in 1958 (Jensen and Jacobson, 1960). Estradiol is mainly generated from female ovaries and also synthesized in liver (Yamamoto et al, 1984), fat (Grodin et al, 1973), testicular (Fritz et al, 1976), adrenal (Davies et al, 1970), breast (Miller and Forrest, 1974), and neural (Ryan et al, 1972) tissues. Thus, ER-mediated estrogen signaling has been observed in both males and females.…”

Section: Overview Of Estrogen Receptors and Estrogen Actionmentioning

confidence: 99%

Interplay of estrogen receptors and FOXA factors in the liver cancer

Zhao

2015

Molecular and Cellular Endocrinology

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Liver cancer is the fifth most common cancer in human with male dominance. Sexual dimorphism of liver cancer is conserved from rodents to humans, which was firstly found in mice in late 1930s and female mice were resistant to liver cancer. Sex hormones were found to affect the incidence of liver cancer in rodents. Estrogen receptor alpha (ERα)-mediated estrogen signaling or androgen receptor-mediated androgen signaling prevents or promotes the growth of rodent liver tumors, respectively. Forkhead box protein A (Foxa) factors, Foxa1 and Foxa2, also known as pioneer transcription factors in liver specification, are essential for both estrogen and androgen signaling by acting as central regulators of sexual dimorphism in liver cancer. This review mainly focuses on the interplay between ERα and FOXA factors in liver cancer, and summarizes recent breakthrough studies in elucidating the mechanisms of sexual dimorphism in liver cancer.

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Estrogen biosynthesis in human liver - A comparison of aromatase activity for C-19 steroids in fetal liver, adult liver and hepatoma tissues of human subjects.

Cited by 19 publications

References 2 publications

Determination and identification of estrogenic compounds generated with biosynthetic enzymes using hyphenated screening assays, high resolution mass spectrometry and off-line NMR

Determination and identification of estrogenic compounds generated with biosynthetic enzymes using hyphenated screening assays, high resolution mass spectrometry and off-line NMR

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

Interplay of estrogen receptors and FOXA factors in the liver cancer

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