Blocking BRE expression in Leydig cells inhibits steroidogenesis by down-regulating 3 beta-hydroxysteroid dehydrogenase
Publication in refereed journal


摘要Conversion of cholesterol to biologically active steroids is a multi-step enzymatic process. Along with some important enzymes, like cholesterol side-chain cleavage enzyme (P450scc) and 3 beta-hydroxysteroid dehydrogenase/isoinerase (3 beta-HSD), several proteins play key role in steroidogenesis. The role of steroidogenic acute regulatory (STAR) protein is well established. A novel protein, BP-E, found mainly in brain, adrenals and gonads, was highly expressed in hyperplastic rat adrenals with impaired steroidogenesis, suggesting its regulation by pituitary hormones. To further elucidate its role in steroidogenic tissues, mouse Leydig tumor cells (mLTC-1) were transfected with BRE antisense probes. Morphologically the BRE antisense cells exhibited large cytoplasmic lipid droplets and failed to shrink in response to human chorionic gonadotropin. Although cAMP production, along with StAR and P450scc mRNA expression, was unaffected in BRE antisense clones, progesterone and testosterone yields were significantly decreased, while pregnenolone was increased in response to human chorionic gonadotropin stimulation or in the presence of 22(R)OH-cholesterol. Furthermore, whereas exogenous progesterone was readily converted to testosterone, pregnenolone was not, suggesting impairment of pregnenolone-to-progesterone conversion, a step metabolized by 3 beta-HSD. That steroidogenesis was compromised at the 3 beta-HSD step was further confirmed by the reduced expression of 3 beta-HSD type I (3 beta-HSDI) mRNA in BRE antisense cells compared with controls. Our results suggest that BRE influences steroidogenesis through its effects on 3 beta-HSD action, probably affecting its transcription.
著者Miao J, Chan KW, Chen GG, Chun SY, Xia NS, Chan JYH, Panesar NS
期刊名稱Journal of Endocrinology
頁次507 - 517
Web of Science 學科類別Endocrinology & Metabolism; ENDOCRINOLOGY & METABOLISM

上次更新時間 2020-12-08 於 23:12