Steroid Sulfotransferase 2A1 Gene Transcription Is Regulated by Steroidogenic Factor 1 and GATA-6 in the Human Adrenal

Saner, Karla; Suzuki, Takashi; Sasano, Hironobu; Pizzey, John; Ho, Clement; Strauss, Jerome F.; Carr, Bruce R.; Rainey, William E.

doi:10.1210/me.2003-0332

Cited by 54 publications

(36 citation statements)

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“…This does not exclude the involvement of other orphan receptors in the regulation of pig SULT2A1 not investigated here. For instance, both steroidogenic factor 1 (SF1) and GATA-6 have been shown to regulate the transcription of human Sult2A1 (Saner et al 2005). Furthermore, this study also highlights the similarity in responsiveness of nuclear receptors of human and pig compared with rodent species.…”

Section: Figurementioning

confidence: 61%

Molecular cloning and regulation of porcine SULT2A1: relationship between SULT2A1 expression and sulfoconjugation of androstenone

Sinclair

Gilmore²,

Lin³

et al. 2006

Journal of Molecular Endocrinology

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Hydroxysteroid sulfotransferase (SULT2A1) is a key enzyme in the testicular and hepatic metabolism of 5 -androstenone, which is a major component of the off-odor and off-flavor in pork known as boar taint. The goals of this study were to determine the role of testicular and hepatic SULT2A1 activity on plasma 5 -androstenone sulfate levels, the accumulation of 5 -androstenone in adipose tissue, and to gain insight into the regulatory control of SULT2A1. Testicular SULT2A1 activity was negatively correlated (r= −0·57; P,0·01) with 5 -androstenone concentrations in fat. The differences observed in SULT2A1 activity warranted investigation into potential genetic variation within porcine SULT2A1. The cDNA sequence of porcine Sult2A1 was determined to be .82% homologous to the human, mouse, and rat Sult2A1 genes. A single nucleotide polymorphism was detected within the coding region of the Sult2A1 from individual testes and liver samples; however, this did not affect the amino acid sequence of the enzyme. Western blot analysis determined that animals with high concentrations of 5 -androstenone in fat and low SULT2A1 activity had corresponding low levels of SULT2A1 protein compared with animals with low levels of 5 -androstenone in fat. Real-time PCR analysis indicated that Sult2A1 mRNA was increased 2·8-fold in animals with high levels of the protein relative to animals with low levels of the protein. Furthermore, we demonstrated the positive role of the nuclear receptors constitutive androstane receptor and pregnane X receptor, as well as the possible role of farnesoid X receptor in the regulation of testicular SULT2A1 activity. Together, the results of this study suggest that differences in SULT2A1 expression can influence 5 -androstenone accumulation in fat.

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Section: Figurementioning

confidence: 61%

Molecular cloning and regulation of porcine SULT2A1: relationship between SULT2A1 expression and sulfoconjugation of androstenone

Sinclair

Gilmore²,

Lin³

et al. 2006

Journal of Molecular Endocrinology

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“…We demonstrated that specific SF1 binding cis-regulatory elements are necessary for trans-activation of SULT2A1 promoter [16]. However, two observations oppose the argument that SF1 is the key factor causing zonal expression of SULT2A1 in the adrenal reticularis.…”

Section: ) Sult2a1mentioning

confidence: 64%

Regulation of the adrenal androgen biosynthesis

Rainey

Nakamura

2008

The Journal of Steroid Biochemistry and Molecular Biology

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144

107

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The human adrenal reticularis produces the so-called adrenal androgens, dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S). As opposed to the cortisol and aldosterone little is known regarding the mechanisms that regulate the production of the adrenal androgens. Several recent studies have shown that type II 3β-hydroxysteroid dehydrogenase (HSD3B2), cytochrome b5 (CYB5), and steroid sulfotransferase (SULT2A1) play an important role in the regulation of adrenal androgen production. Specifically, adrenal production of DHEA-S is correlated with reticularis expression of SULT2A1 and CYB5. In contrast, HSD3B2 has an inverse correlation with adrenal androgen production likely due to its unique ability to remove precursors from the pathway leading to DHEA. Therefore, its expression is limited to the adrenal glomerulosa/fasciculata but not in reticularis. The differential expression of these three proteins appears to be critical for reticularis function. In this review, we focus on studies that have begun to define the mechanisms regulating the transcription of these genes. Understanding the mechanisms controlling differential expression of these proteins should provide novel information about the human adrenal reticularis and its production of DHEA and DHEA-S. KeywordsAdrenal; Androgen; Cytochrome b5; DHEA-sulfotransferase; 3β-hydroxysteroid dehydrogenase II. Background & SignificanceThe fetal adrenal produces large amounts of dehydroepiandrosterone (DHEA) and DHEAsulfate (DHEAS) during fetal development (Fig. 1). DHEA-S concentrations are also high in the newborn (Fig. 1) [1]. However, by age 1, the specialized fetal zone is lost and replaced by the definitive adrenal cortex, which initially synthesizes little DHEA-S (Fig. 1). Hence, DHEA-S production declines precipitously during the first months of life and remains low until adrenarche commences at about age 6-8 [2]. This rise in the circulating concentrations of DHEA and DHEA-S is the biochemical hallmark of adrenarche [3]. Importantly, the rise in DHEA-S occurs prior to the increase of either estrogens or androgens associated with puberty [4]. Circulating DHEA-S concentrations continue to rise and peak during the second decade of life, with levels being higher in males than in females (Fig. 1) [3,5]. While circulating concentrations of DHEA and DHEA-S rise progressively in adrenarche, cortisol and ACTH concentrations do not change significantly in this period, indicating that adrenarche is not simply a global activation of the pituitary-adrenal axis.Correspondence and reprint requests addressed to: William E Rainey, Ph.D. Department of Physiology, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912,, Email: E-mail: wrainey@mcg.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its f...

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“…GATA-6 is well-known to be expressed in the zona reticularis and fasciculata of the adult adrenal cortex [5]. GATA-6 was also demonstrated to play an important role in cortisol production by regulating HSD3B2 genes transcription [7].…”

Section: Discussionmentioning

confidence: 99%

“…GATA-6 is postulated to play an important role in both the adrenal cortisol and androgen production by regulating steroid sulfotransferase 2A1 (SULT2A1), cytochrome b5 (CYB5), and 3beta-hydroxysteroid dehydrogenase type 2 (HSD3B2) genes transcription [5][6][7]. However, the distribution of GATA-6 expression in the two zones of the fetal adrenocortex especially in relation to its development, as well as its developmental changes after the birth, are largely unknown.…”

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confidence: 99%

Transcription Factor GATA-6 in the Human Adrenocortex: Association with Adrenal Development and Aging

2007

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Abstract. Transcription factor GATA-6 has been demonstrated to be expressed in the human fetal and adult adrenal cortex and has been postulated to play an important role in adrenal steroid biosynthesis. However, the status for GATA-6 expression has not been examined in detail especially in relation to adrenal development and aging. Therefore, in this study, we analyzed GATA-6 expression in 11 human fetal adrenals and 19 adrenal glands after birth using immunohistochemistry. In the fetal adrenals, the status of GATA-6 immunoreactivity in the definitive zone was significantly and directly correlated with ages of development (P<0.05) but in the fetal zone was significantly and inversely correlated with ages of development (P<0.05). After birth, GATA-6 was more abundant in the zona fasciculata compared to other zones (P<0.05) but was not related to aging of the subject. These results suggest that GATA-6 expression is involved in the regulation of corticosteroid production in both the human fetal and adult adrenals, and the changes of intra-adrenal GATA-6 expression in the human fetal adrenal plays important roles in developmental changes of both the definitive and fetal zones.

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Steroid Sulfotransferase 2A1 Gene Transcription Is Regulated by Steroidogenic Factor 1 and GATA-6 in the Human Adrenal

Cited by 54 publications

References 74 publications

Molecular cloning and regulation of porcine SULT2A1: relationship between SULT2A1 expression and sulfoconjugation of androstenone

Molecular cloning and regulation of porcine SULT2A1: relationship between SULT2A1 expression and sulfoconjugation of androstenone

Regulation of the adrenal androgen biosynthesis

Transcription Factor GATA-6 in the Human Adrenocortex: Association with Adrenal Development and Aging

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