Sorbitol dehydrogenase expression is regulated by androgens in the human prostate

Abstract

Abstract.Sorbitol is an intermediate in the polyol pathway, which converts from glucose to fructose by sorbitol dehydrogenase (SORD). Androgens are essential for the development of prostate cancer. We studied castration-induced gene expression changes in the human prostate using the GeneChip array, and identified SORD as being androgen-regulated in the human prostate. A putative androgen-responsive regulatory region at the SORD 5' promoter was identified using promoter deletion constructs in a luciferase reporter assay in COS-7 cells. Chromatin immunoprecipitation assay was used to assess the binding of androgen receptor to suggested androgen responsive regulatory region. Finally, the expression of SORD in the human prostate was evaluated in 29 prostate tissue samples by immunohistochemistry. The expression of SORD decreased after castration. Androgen supplementation to the LNCaP prostate cancer cell line led to a 7.5-fold increase in SORD mRNA expression. Furthermore, a chromatin immunoprecipitation assay proved that the androgen receptor can bind to this putative androgen-responsive regulatory region. Finally, the expression of SORD in the human prostate was localised to epithelial cells of both benign and malignant prostate tissue by immunohistochemistry. In prostate cancer, increased immunostaining was associated with high Gleason patterns and high serum prostate-specific antigen concentrations. These results show that SORD is a novel androgen-regulated gene in the human prostate and suggest the need for more detailed analysis of the physiological role of SORD in the prostate.

Biological role of fructose in the male reproductive system: Potential implications for prostate cancer

“…Ortiz et al detected a significant reduction of fructose secretion from the SVs of castrated guinea pigs at 4 (9.8 ± 4.2 mg/100 mg) and 8 (4.3 ± 3.7 mg/100 mg) weeks postcastration, as compared with normal adult guinea pigs (54.5 mg/100 mg of SV) 51 . The loss of fructose production may be mediated by reduced expression of SORD since it is known to be an androgen‐regulated gene 52 . Taken together, these data show that age and androgen exposure can affect reproductive physiology in men by directly altering SV fructose production.…”

“…51 The loss of fructose production may be mediated by reduced expression of SORD since it is known to be an androgen-regulated gene. 52 >6.0; sugary breakfast snacks <1.9, 1.9-4.9, >4.9; candy and chocolate <0. the molecular mechanisms involved in pathologies such as PCa, in which androgen dependence, age, and potentially the metabolism of fructose, play an important role.…”

“…The first is that the high fructose levels result from de novo synthesis of fructose by the tumors through the polyol pathway. Indeed, Szabó and colleagues reported that SORD expression was upregulated by the activation of androgen receptor signaling in prostate tissues from castrated humans and the LNCaP PCa cell line 52 . The high expression of SORD in PCa cells correlates with high Gleason scores and high prostate‐specific antigen (PSA) levels in PCa tissues compared with those in their benign counterparts.…”

Oxidoreductase enzymes: Characteristics, applications, and challenges as a biocatalyst

“…This enzyme is located mainly in the cytoplasm and mitochondria of liver, kidney, and seminal vesicle cells, and it is used as an indicator of prostate cancer, as it is highly regulated by androgens. 112 Another dehydrogenase used as a cancer indicator due to its high specificity is l-lactate dehydrogenase (EC 1.1.1.27), widely distributed in human tissues, whose substrates are pyruvate and l-lactate during homolactic fermentation and gluconeogenesis processes, respectively. Overexpression of this dehydrogenase can be a marker for different types of tumors.…”

Applications of Oxidoreductases

“…Two dehydrogenases, specifically, sorbitol dehydrogenase (SDH) and LDH, are used for cancer prognosis [3]. Reports suggested that in prostate cancer [6], and precancerous colorectal neoplasms [7], an abnormal serum concentration of SDH has been observed. Additionally, an enhanced level of SDH can be observed in acute liver damage and parenchymal hepaticdiseases [3].…”