Regulation of lactate production and glucose transport as well as of glucose transporter 1 and lactate dehydrogenase A mRNA levels by basic fibroblast growth factor in rat Sertoli cells

Abstract

By using cultured rat Sertoli cells as a model, both the action of basic fibroblast growth factor (bFGF) on lactate production and the site of this action were studied. bFGF stimulated Sertoli cell lactate production in a dosedependent manner (basal: 7·3 0·5; 0·1 ng/ml bFGF: 7·5 0·5; 1 ng/ml bFGF: 7·5 0·6; 10 ng/ml bFGF: 10·3 1·0; 30 ng/ml bFGF: 15·2 1·5; 50 ng/ml bFGF: 15·4 1·6 µg/µg DNA). Two major sites for the action of this growth factor were identified. First, bFGF was shown to exert short-and long-term stimulatory effects on glucose transport (basal: 1170 102; 30 ng/ml bFGF for 120 min: 1718 152 and basal: 718 64; 30 ng/ml bFGF for 48 h: 1069 69 d.p.m./µg DNA respectively). Short-term bFGF stimulation of glucose transport was not inhibited by the protein synthesis inhibitor cycloheximide. These results indicate that short-term bFGF stimulation of glucose uptake does not involve an increase in the number of glucose transporters. On the other hand, stimulation with bFGF for periods of time longer than 12 h increased glucose transporter 1 (GLUT1) mRNA levels. These increased mRNA levels were probably ultimately responsible for the increments in glucose uptake that are observed in long-term treated cultures. Secondly, bFGF increased lactate dehydrogenase (LDH) activity (basal: 31·0 1·4; 30 ng/ml bFGF: 45·7 2·4 mIU/µg DNA). The principal subunit component of those LDH isozymes that favors the transformation of pyruvate to lactate is subunit A. bFGF increased LDH A mRNA levels in a dose-and time-dependent manner. In summary, the results presented herein show that glucose transport, LDH activity and GLUT1 and LDH A mRNA levels are regulated by bFGF to achieve an increase in lactate production. These observed regulatory actions provide unequivocal evidence of the participation of bFGF in Sertoli cell lactate production which may be related to normal germ cell development.

Evaluation of LDH Activity and Its Relationship with Fructose Levels in Seminal Plasma of Normospermic and Asthenospermic Males

“…Grootegoed et al showed the conversion of glucose to lactate by Sertoli cells (27). This locally produced lactate is augmented by paracrine/autocrine factors such as transforming growth factor β, epidermal growth factor, basic fibroblast growth factor, tumor necrosis factor α and interleukin 1α (28)(29)(30)(31)(32), which are involved in cell-cell communications in the testis (33). These factors target glucose uptake and total LDH activity for stimulating lactate production.…”

Lactate dehydrogenase-5 (LDH-5) overexpression in non-small-cell lung cancer tissues is linked to tumour hypoxia, angiogenic factor production and poor prognosis

“…For example, acidification of the tumour environment by lactate may account for bFGF overexpression (D'Arcangelo et al, 2000). On the other hand, a direct effect of bFGF on LDH cellular levels has been recently shown by Riera et al (2002).…”

Assessment of the roles of mitogen-activated protein kinase and phosphatidyl inositol 3-kinase/protein kinase B pathways in the basic fibroblast growth factor regulation of Sertoli cell function

“…These results suggested that both pathways might be participating in the regulation of the final biological response. Riera et al (2002) showed that increments in glucose uptake and in LDH activity are part of the mechanisms utilized by bFGF to increase lactate production. Therefore, we next analyzed the possible participation of MAPK-and PI3K/PKBsignaling pathways on the regulation of these two metabolic steps that are important contributors to the ability of a cell to increase its lactate production.…”