Diagram of the pathways of human steroidogenesis

Häggström, Mikael; Richfield, David

doi:10.15347/wjm/2014.005

Cited by 60 publications

(19 citation statements)

References 4 publications

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“…A similar mechanism has been postulated by several studies to occur in the somatic mutations of the G protein‐activated inward rectifier potassium channel 4 (GIRK4, encoded by the KCNJ5 gene), the sodium/potassium‐transporting ATPase subunit alpha‐1 ( ATP1A1 ) and the plasma membrane calcium‐transporting ATPase 3 (PMCA3, encoded by the gene ATP2B3 ) . Mutations in the KCNJ5, ATP1A1 and ATP2B3 would ultimately lead to increase aldosterone biosynthesis in APA, basically by allowing a higher permeability of the ion pore at the cellular membrane …”

Section: Somatic Mutations Of Ion‐channels In Pa Tissuesmentioning

confidence: 53%

“…43,50 Mutations in the KCNJ5, ATP1A1 and ATP2B3 would ultimately lead to increase aldosterone biosynthesis in APA, basically by allowing a higher permeability of the ion pore at the cellular membrane. 9,43 Of particular interest, the mRNA levels of PCP4 and CYP11B2 have been reported to be directly correlated to those of mutated KCNJ5, which in turn can be directly correlated to peripheral plasma aldosterone levels and inversely correlated to serum potassium levels in APA patients, which reinforces the notion of calcium-related aldosterone biosynthesis as it provides evidence of these mechanisms in vivo. 23…”

Section: Somatic Mutations Of Ion-channels In Pa Tissuesmentioning

confidence: 65%

“…The two most important adrenocortical hormones, however, are forged by the mitochondrial enzymes 11beta‐hydroxylase ( CYP11B1 ) present in the zona fasciculata of the adrenal cortex and responsible for the biosynthesis of cortisol, and aldosterone synthase ( CYP11B2 ) present in exclusively in the zona glomerulosa of the adrenal cortex, and which produces aldosterone. This figure was adapted from a previous work reported by Häggström and Richfield, and supported by additional referrences …”

Section: The Expression and Distribution Of Steroidogenic Enzymes In mentioning

confidence: 77%

“…This figure was adapted from a previous work reported by Häggström and Richfield, and supported by additional referrences. [6][7][8][9]…”

Section: Figurementioning

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: Somatic Mutations Of Ion‐channels In Pa Tissuesmentioning

confidence: 53%

Section: Somatic Mutations Of Ion-channels In Pa Tissuesmentioning

confidence: 65%

Section: The Expression and Distribution Of Steroidogenic Enzymes In mentioning

confidence: 77%

“…This figure was adapted from a previous work reported by Häggström and Richfield, and supported by additional referrences. [6][7][8][9]…”

Section: Figurementioning

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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“…PKA phosphorylates steroidogenic acute regulatory protein (STAR), which transports cholesterol into mitochondria, where cholesterol is transformed into pregnenolone under the catalysis of P450 cholesterol side chain cleavage (P450scc). Pregnenolone is converted to testosterone under the catalysis of a series of enzymes, including 3b-hydroxysteroid dehydrogenase (3b-HSD) and 17b-HSD in the smooth endoplasmic reticulum (Häggström & Richfield 2014). Here, STAR-mediated transportation of cholesterol into mitochondia is the ratelimiting step, and thus, STAR is the rate-limiting protein for testosterone synthesis (Miller & Bose 2011).…”

Section: Introductionmentioning

confidence: 99%

HIF 1 inhibits STAR transcription and testosterone synthesis in murine Leydig cells

Wang

Zou

Yang

et al. 2019

Journal of Molecular Endocrinology

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Hypoxia-inducible factor-1 (HIF1) is a critical transcription factor involved in cell response to hypoxia. Under physiological conditions, its 'a' subunit is rapidly degraded in most tissues except testes. HIF1 is stably expressed in Leydig cells, which are the main source of testosterone for male, and might bind to the promoter region of steroidogenic acute regulatory protein (STAR), which is necessary for the testosterone synthesis, according to software analysis. This study aims to identify the binding sites of HIF1 on Star promoter and its transcriptional regulation of STAR to affect testosterone synthesis. Testosterone level and steroid synthesis-related proteins were determined in male Balb/C mice exposed to hypoxia (8% O 2 ). While HIF1 was upregulated, the testosterone level was significantly decreased. This was further confirmed by in vitro experiments with rat primary Leydig cells or TM3 cells exposed to hypoxia (1% O 2 ), CoCl 2 or DFX to raise HIF1. The decline of testosterone was reversed by pregnenolone but not cAMP, indicating the cholesterol transport disorder as the main cause. In agreement, STAR expression level was decreased in response to HIF1, while 3b-hydroxysteroid dehydrogenase, 17b-hydroxysteroid dehydrogenase and p450scc did not exhibit significant changes. By ChIP, EMSA supershift and dual-luciferase reporter assays, HIF1 was found to bind to the Star promoter region and repress the expression of STAR. Mutation assays identified three HIF1-binding sites on mouse Star promoter. These findings indicate that HIF1 represses STAR transcription through directly binding to the Staar promoter at −2082/−2078, −2064/−2060 and −1910/−1906, leading to the negative regulation of testosterone synthesis.

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Insect Sterols and Steroids

Lafont,

Dinan

2024

Advances in Experimental Medicine and Biology

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Diagram of the pathways of human steroidogenesis

Cited by 60 publications

References 4 publications

Dissecting the molecular pathways of primary aldosteronism

Dissecting the molecular pathways of primary aldosteronism

HIF 1 inhibits STAR transcription and testosterone synthesis in murine Leydig cells

Insect Sterols and Steroids

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