TGF-β Inhibits<i>CYP17</i>Transcription in H295R Cells Acting via Activin Receptor-Like Kinase 5

Derebecka-Holysz, Natalia; Lehmann, Tomasz P.; Hołysz, Marcin; Trzeciak, Wiesław H.

doi:10.1080/07435800903137050

Cited by 6 publications

(1 citation statement)

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“…In bovine granulosa cells, TGFβ1 stimulates estradiol production by increasing CYP19 mRNA levels and aromatase activity while inhibiting progesterone production by suppressing StAR, CYP11A1, and 3β-HSD1 transcription [16]. Further, TGFβ1 decreases P450c17α activity in H295R cells by repressing CYP17 gene expression via the activation of activin receptor-like kinase 5 (ALK5) [17]. Finally, mutations in PDGF target genes result in altered hormone production in the testis and ovaries [14] while aberrant FGF9 expression stimulates testosterone production in mouse Leydig cells [12].…”

Section: Introductionmentioning

confidence: 99%

The interplay between bioactive sphingolipids and steroid hormones

Lucki

Sewer

2010

Steroids

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Steroid hormones regulate various physiological processes including development, reproduction, and metabolism. These regulatory molecules are synthesized from cholesterol in endocrine organs -such as the adrenal glands and gonads- via a multi-step enzymatic process that is catalyzed by the cytochrome P450 superfamily of monooxygenases and hydroxysteroid dehydrogenases. Steroidogenesis is induced by trophic peptide hormones primarily via the activation of a cAMP/protein kinase A (PKA)-dependent pathway. However, other signaling molecules, including cytokines and growth factors, control the steroid hormone biosynthetic pathway. More recently, sphingolipids, including ceramide, sphingosine-1-phosphate, and sphingosine, have been found to modulate steroid hormone secretion at multiple levels. In this review, we provide a brief overview of the mechanisms by which sphingolipids regulate steroidogenesis. In addition, we discuss how steroid hormones control sphingolipid metabolism. Finally, we outline evidence supporting the emerging role of bioactive sphingolipids in various nuclear processes and discuss a role for nuclear sphingolipid metabolism in the control of gene transcription.

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