• 2018-07
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  • Recently we have observed that pharmacological PPAR


    Recently, we have observed that pharmacological PPARα and PPARβ/δ activation regulates the expression of genes involved in FA metabolism such as FAT/CD36, CPT1, LCAD and MCAD in Sertoli cells. We have also observed that PPARβ/δ activation can simultaneously regulate the expression of the above-mentioned genes and lactate production. These results were interpreted as a reflection of a coordinated mechanism which will ensure the concomitant provision of energy to Sertoli and germ cells (Regueira et al., 2014). The mechanisms involved in a possible activation of this nuclear receptor under physiological conditions, which may include hormonal regulation, have not been analyzed yet in Sertoli cells. In the present study, we investigated whether FSH and bFGF are able to regulate molecular mechanisms involved in FA metabolism and in mitochondrial biogenesis. In addition, in the case that FA metabolism and mitochondrial biogenesis are regulated by FSH and bFGF, if PPARβ/δ activation has any role in this hormonal regulation of Sertoli cell energetic metabolism.
    Materials and methods
    Discussion Energetic metabolism in the seminiferous tubule has been considered to have features of its own. As mentioned in the introduction, it has been shown that Sertoli cells mainly utilize FA as its energy source (Jutte et al., 1985). Few studies have dealt with FA metabolism in Sertoli cells since Jutte’s early work. To this respect, a mitochondrial FA oxidation system (Fukasawa et al., 2010) and the presence of proteins which transport fatty acids – FAT/CD36 (Gillot et al., 2005) and CPT1 (Adams et al., 1998) – in Sertoli cells have been demonstrated. However, no studies have explored the hormonal regulation of these genes. We have recently observed that activation of PPARα and PPARβ/δ in Sertoli cells regulates the expression of genes involved in fatty Dapoxetine HCl sale transport and metabolism (Regueira et al., 2014). Considering that FA oxidation is an important energy source in Sertoli cells, it may be assumed that this process must be strictly regulated. The last assumption is particularly pertinent to hormones such as FSH – the master hormone in the regulation of Sertoli cell physiology – and bFGF – a representative member of the locally produced testicular factors. In Sertoli cells, FAT/CD36 has been found in the vicinity of residual bodies engulfed by these cells during the spermiation process (Gillot et al., 2005). It has been proposed that FAT/CD36 may not only be important in FA uptake but also in the phagocytosis of apoptotic germ cells and residual bodies, elements that probably represent an additional supply of FA available for ATP production in Sertoli cells (Xiong et al., 2009). Our results show that FSH, but not bFGF, increases FAT/CD36 mRNA levels in Sertoli cells probably favoring the availability of FA as building blocks for complex lipids. As for the genes involved in FA oxidation, we observed that FSH stimulates both the expression of CPT1 and MCAD, while bFGF only stimulates CPT1 mRNA levels. However, only bFGF stimulates CPT1 protein levels. In accordance with the positive regulation of CPT1 mRNA and protein levels, an increase in fatty acid oxidation under bFGF treatment was observed. This result pointed out that bFGF has a role in the ability of Sertoli cells to metabolize lipid matter in order to obtain energy. Simultaneously, bFGF stimulates lactate production which is exported and used as energy source by developing germ cells. On the other hand, FSH decreased fatty acid oxidation. This result was not unexpected as the anabolic effects of FSH are well recognized. To this respect, it has been demonstrated that FSH significantly stimulates acetate incorporation into triglycerides and phospholipids by regulating lipid esterification (Guma et al., 1997). In this way, FSH promotes on the one hand the synthesis of essential enzymes necessary to obtain energy and concomitantly the synthesis of lipids that may be essential to maintain spermatogenesis.