GATA6, SF1, NGFIB and DAX1 in the remodeled subcapsular zones in primary aldosteronism

Nakamura, Yasuhiro; Kurotaki, Yumi; Ise, Kazue; Felizola, Saulo J.A.; McNamara, Keely May; Sasano, Hironobu

doi:10.1507/endocrj.ej13-0103

Cited by 6 publications

(8 citation statements)

References 28 publications

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“…In contrast to APA, IHA may be regarded as non‐neoplastic PA. In IHA cases, the specimens available for histopathological examination have become increasingly rare due to the predominant mode of treatment being medical therapy alone rather than surgical intervention . The histopatological features of IHA are hyperplastic changes of the ZG .…”

Section: The Adrenal Histopathology Of Pamentioning

confidence: 99%

“…The mRNA expression of steroidogenic enzymes can be regulated by several transcription factors in the cellular nucleus . Angiotensin II (AngII) and K + effects culminate with synthesis of new transcription factors, such as the neuronal growth factor‐induced clone B (NGFI‐B) family members that have been reported to regulate CYP11B2 expression .…”

Section: The Transcriptional Regulators Of Steroidogenic Enzymes In Amentioning

confidence: 99%

“…Angiotensin II (AngII) and K + effects culminate with synthesis of new transcription factors, such as the neuronal growth factor‐induced clone B (NGFI‐B) family members that have been reported to regulate CYP11B2 expression . It was previously reported that the HSD3B2 promoter contains four consensus GATA regulatory motifs, an important target for GATA factors including GATA6, and functional effects of GATA6 on HSD3B2 have been previously demonstrated with co‐expression of GATA6 and steroidogenic factor 1 (SF1), which did result in a synergistic activation of HSD3B2 promoter activity . The GATA6/SF1 signaling pathway above was also reported to be negatively regulated by DAX1 in their upstream because DAX1 was reported to oppose SF1‐activated transcription and abolish the ability of GATA6/SF1 to increase their reporter activities of various types of steroidogenic enzymes in the adrenal gland .…”

Section: The Transcriptional Regulators Of Steroidogenic Enzymes In Amentioning

confidence: 99%

“…In IHA cases, the specimens available for histopathological examination have become increasingly rare due to the predominant mode of treatment being medical therapy alone rather than surgical intervention. 5 The histopatological fea-tures of IHA are hyperplastic changes of the ZG. 2 However, the ZG of the adrenal glands adjacent to the APA is expected to show atrophy due to the suppressed renin-angiotensin system but frequently associated with hyperplastic changes.…”

Section: The Adrenal Histopathology Of Pamentioning

confidence: 99%

“…The mRNA expression of steroidogenic enzymes can be regulated by several transcription factors in the cellular nucleus. 5,19 Angiotensin II (AngII) and K + effects culminate with synthesis of new transcription factors, such as the neuronal growth factor-induced clone B (NGFI-B) family members that have been reported to regulate CYP11B2 expression. 19 It was previously reported that the HSD3B2 promoter contains four consensus GATA regulatory motifs, an important target for GATA factors including GATA6, and functional effects of GATA6 on HSD3B2 have been previously demonstrated with co-expression of GATA6 and steroidogenic factor 1 (SF1), which did result in a synergistic activation of HSD3B2 promoter activity.…”

Section: The Transcriptional Regulators Of Steroidogenic Enzymes In Amentioning

confidence: 99%

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Dissecting the molecular pathways of primary aldosteronism

Nakamura

Felizola

Satoh

et al. 2014

Pathology International

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The great majority of the cases clinically diagnosed as primary aldosteronism (PA) have been caused by aldosterone-producing adenoma (APA) or idiopathic hyperaldosteronism (IHA). The differential diagnosis of both subtypes of PA is important due to the different therapeutic modes but clinically it is sometimes difficult. It is also important to understand the morphological features of these two subtypes with special emphasis upon differences of the status for aldosterone biosynthesis. In the last decade, molecular mechanisms of PA including the aberrant expression of G-protein coupled receptors (GPCRs), key regulators of the intracellular calcium signaling pathway and somatic mutations of ion channels, have been revealed and our understanding of the molecular pathways involved in excessive aldosterone production has been markedly advanced. In addition, newly developed monoclonal antibodies specific to the isoform of adrenal steroidogenic enzymes have demonstrated the novel profiles of adrenal steroidogenesis in PA. These novel findings indicate that the molecular mechanisms on the onset and pathophysiology of PA are more complicated than previously considered and further clarification of clinical relevance of these findings is required at this juncture.

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Section: The Adrenal Histopathology Of Pamentioning

confidence: 99%

Section: The Transcriptional Regulators Of Steroidogenic Enzymes In Amentioning

confidence: 99%

Section: The Transcriptional Regulators Of Steroidogenic Enzymes In Amentioning

confidence: 99%

Section: The Adrenal Histopathology Of Pamentioning

confidence: 99%

Section: The Transcriptional Regulators Of Steroidogenic Enzymes In Amentioning

confidence: 99%

See 3 more Smart Citations

Dissecting the molecular pathways of primary aldosteronism

Nakamura

Felizola

Satoh

et al. 2014

Pathology International

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3β-hydroxysteroid dehydrogenase isoforms in human aldosterone-producing adenoma

Konosu-Fukaya

Nakamura

Satoh

et al. 2015

Molecular and Cellular Endocrinology

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It has become important to evaluate the possible involvement of 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1) and 2 (HSD3B2) isoforms in aldosterone-producing adenoma (APA). In this study, we studied 67 and 100 APA cases using real-time quantitative PCR (qPCR) and immunohistochemistry, respectively. Results of qPCR analysis demonstrated that HSD3B2 mRNA was significantly more abundant than HSD3B1 mRNA (P < 0.0001), but only HSD3B1 mRNA significantly correlated with CYP11B2 (aldosterone synthase) mRNA (P < 0.0001) and plasma aldosterone concentration (PAC) of the patients (P < 0.0001). Results of immunohistochemistry subsequently revealed that HSD3B2 immunoreactivity was detected in the great majority of APA but a significant correlation was also detected between HSD3B1 and CYP11B2 (P < 0.0001). In KCNJ5 mutated APA, CYP11B2 mRNA (P < 0.0001) and HSD3B1 mRNA (P = 0.011) were significantly higher than those of wild type APA. These results suggest that HSD3B1 is involved in aldosterone production, despite its lower levels of expression compared with HSD3B2, and also possibly associated with KCNJ5 mutation in APA.

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Ovarian neuroendocrine tumor metastases can induce estrogen production in postmenopausal patients

Mulders,

van Velthuysen,

Roes

et al. 2024

European Journal of Endocrinology

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Neuroendocrine tumors (NET) are malignant neoplasms that can be associated with specific hormonal syndromes. We describe a novel syndrome of postmenopausal vaginal bleeding and ovarian estradiol overproduction due to ovarian NET localizations. An extensive workup was performed for two index patients with ovarian metastases of small bowel neuroendocrine tumors and symptoms of postmenopausal vaginal bleeding. Clinically significant ovarian estrogen production was demonstrated by a combination of ovarian vein sampling and normalization of circulating estrogen levels after oophorectomy. Immunohistochemical analyses revealed marked aromatase immunoactivity in the ovarian NET cells, while CYP17A1 and SF-1 were detected in the adjacent ovarian stromal cells but not the NET cells. Ex vivo and in vivo endocrine tests were unable to identify a paracrine mechanism of ovarian estradiol overproduction by NET cells. A retrospective search of electronic medical records revealed that 21% (14/66) of postmenopausal patients with an ovarian NET localization reported symptoms of vaginal blood loss. Together, these findings support the presence of a novel NET-associated hormonal syndrome.

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GATA6, SF1, NGFIB and DAX1 in the remodeled subcapsular zones in primary aldosteronism

Cited by 6 publications

References 28 publications

Dissecting the molecular pathways of primary aldosteronism

Dissecting the molecular pathways of primary aldosteronism

3β-hydroxysteroid dehydrogenase isoforms in human aldosterone-producing adenoma

Ovarian neuroendocrine tumor metastases can induce estrogen production in postmenopausal patients

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