Adrenocortical pregnenolone binding activity resides with estrogen sulfotransferase.

Lee, Y. C.; Park, Chang‐Shin; Komatsu, Katsutoshi; Kwack, Jae Jung; Strott, Charles A.

doi:10.1210/endo.136.1.7828553

Cited by 6 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…gpEST is also known to specifically bind to E2 with a relatively high affinity. Pregnenolone and E2 effectively compete for binding to gpEST, but pregnenolone, which is not sulfonated by gpEST, does not inhibit sulfonation of E2 (41). These results suggest that EST may participate in steroid production as a pregnenolone binding carrier protein in the human adrenal gland as described above.…”

Section: Discussionmentioning

confidence: 56%

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

View full text Add to dashboard Cite

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)

show abstract

Section: Discussionmentioning

confidence: 56%

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

View full text Add to dashboard Cite

show abstract

“…Pregnenolone and 17/3-estradiol effectively compete with each other for binding to gpEST; however, pregnenolone, which is not sulfonated by EST, does not inhibit the sulfonation of 17/3-estradiol (82). The latter is a perplexing observation that is difficult to comprehend.…”

Section: A Estrogen Sulfotransferase (Est)mentioning

confidence: 98%

“…Finally, an observation concerning gpEST that, while interesting, is also perplexing: in addition to high-affinity 17/3-estradiol-binding activity, gpEST will also specifically bind pregnenolone with a relatively high affinity (K d ~ 100 nM); furthermore, the pregnenolone-binding activity, as is the case for 17/3-estradiol binding, is dependent on the presence of 3',5'-ADP (82). Pregnenolone and 17/3-estradiol effectively compete with each other for binding to gpEST; however, pregnenolone, which is not sulfonated by EST, does not inhibit the sulfonation of 17/3-estradiol (82).…”

Section: A Estrogen Sulfotransferase (Est)mentioning

confidence: 99%

Steroid sulfotransferases

Strott¹

1996

Endocrine Reviews

View full text Add to dashboard Cite

“…Since the mechanisms of cytochrome P450 and steroiddehydrogenase mediated steroid biosynthesis were first described, and the importance of the transfer of steroid intermediates from mitochondrial to microsomal sites of enzyme activity (and back again) were first noted, little attention has been directed to addressing how this might be achieved. Although the question has certainly been asked whether binding proteins have a role [31±34], in some cases it seems clearer [31] than in others [35]. It is also possible that a carrier protein could be involved with intercellular steroid transport.…”

Section: Cell Type Specific Expression Of Izag/ppmrmentioning

confidence: 99%

Identification of the rat adrenal zona fasciculata/reticularis specific protein, inner zone antigen (IZAg), as the putative membrane progesterone receptor

Raza

Takemori

Tojo

et al. 2001

European Journal of Biochemistry

View full text Add to dashboard Cite

Using immunological methods, a protein specific to the inner zones of the rat adrenal cortex, and called inner zone antigen (IZAg), was previously shown to have two interrelated forms of 26 kDa (IZAg1) and 55±60 kDa (IZAg2), and to have an action on steroid hydroxylation. After twodimensional gel electrophoresis, and immunoaffinity column purification, N-terminal amino-acid analysis showed that the first 12 amino acids were identical to those of a recently described putative membrane located progesterone receptor (PPMR). RT-PCR was then used to generate the cDNA of this protein, using RNA extracted from rat adrenals. A glutathione S-transferase (GST)-fusion construct was expressed in Escherichia coli, and shown to generate an immunoreactive product of molecular mass consistent with its identification as IZAg1. More detailed examination of the distribution of this protein, not only in the zona fasciculata/reticularis of the adrenal cortex, but also in the Leydig cell, kidney and liver, suggest it may have a role in steroid hormone synthesis and/or metabolism.

show abstract

Adrenocortical pregnenolone binding activity resides with estrogen sulfotransferase.

Cited by 6 publications

References 0 publications

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

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

Steroid sulfotransferases

Identification of the rat adrenal zona fasciculata/reticularis specific protein, inner zone antigen (IZAg), as the putative membrane progesterone receptor

Contact Info

Product

Resources

About