FSH stimulation of the production of pyruvate and lactate by rat Sertoli cells may be involved in hormonal regulation of spermatogenesis (original) (raw)
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Regulation of survival of rat pachytene spermatocytes by lactate supply from Sertoli cells
Journal of reproduction and fertility, 1982
During incubation of fragments of seminiferous tubules in the absence of glucose, pachytene spermatocytes and round spermatids died within 24 h, while Sertoli cells were still viable. The germ cells survived for at least 72 h in seminiferous tubule fragments which were incubated in the presence of glucose. Lactate rather than glucose is essential for [3H]uridine incorporation and survival of isolated pachytene spermatocytes. However, if the spermatocytes were incubated in the presence of Sertoli cells, glucose maintained the incorporation of [3H]uridine into the germ cells. Sertoli cells secreted lactate in the presence of glucose and the lactate secretion was stimulated 2--4-fold by FSH. It is concluded that the activity and survival of pachytene spermatocytes in vitro can be regulated by the supply of lactate from Sertoli cells.
Protein synthesis by isolated pachytene spermatocytes in the absence of Sertoli cells
The Journal of experimental zoology, 1985
Isolated rat pachytene spermatocytes were incubated in chemically defined medium supplemented with pyruvate and lactate, which are known to be essential energy substrates for these germ cells. Protein synthesis by the isolated cells was investigated by means of two-dimensional polyacrylamide gel electrophoresis. The electrophoretic patterns of (35S)-labeled proteins, synthesized by the pachytene spermatocytes during incubation in the presence of (35S)methionine either from 0-2 h or from 24-26 h after isolation, were almost completely identical. The patterns of newly synthesized proteins of freshly isolated spermatocytes and spermatids, however, showed several stage-specific proteins in addition to many proteins common to both spermatogenic cell types. Hence, it was concluded that a stage-specific pattern of protein synthesis can be maintained by pachytene spermatocytes during incubation for a period of 24 h in the absence of Sertoli cells but in the presence of a proper energy source.
Journal of Andrology, 2011
The role of dihydrolipoamide dehydrogenase (DLD), the E3 subunit of the pyruvate dehydrogenase complex (PDHc) in hamster sperm capacitation and acrosome reaction has been implicated previously. In this study, attempt has been made to understand DLD/PDHc involvement from the perspective of pyruvate/lactate metabolism. Inhibition of DLD was achieved by the use of a specific inhibitor, 5-methoxyindole-2-carboxylic acid. It was seen that 5-methoxyindole-2-carboxylic acid-treated spermatozoa with inhibited DLD (and PDHc) activity had lactate accumulation, which caused an initial lowering of the intracellular pH and calcium and an eventual block in capacitation and acrosome reaction. Collectively, the data reveal a significant contribution of the metabolic enzymes DLD and PDHc to lactate regulation in hamster spermatozoa during capacitation and acrosome reaction. Additionally, the importance of lactate regulation in the maintenance of sperm intracellular pH and calcium, two important physiologic factors essential for sperm capacitation and acrosome reaction, has also been established.
Intercellular pathway of leucine catabolism in rat spermatogenic epithelium
The Biochemical journal, 1985
A unique intercellular pathway of leucine catabolism was observed in vitro in rat spermatogenic epithelium. Sertoli cells convert leucine via transmination into 4-methyl-2-oxovalerate, and spermatocytes and spermatids reduce exogenous 4-methyl-2-oxovalerate to 2-hydroxy-4-methylvalerate, which is then released by the spermatogenic cells. The NADH-dependent reduction of 4-methyl-2-oxovalerate could be catalysed by the male-germ-cell-specific lactate dehydrogenase isoenzyme LDH-C4 in the cytosol of the spermatogenic cells, concomitant with the NAD+-dependent conversion of exogenous lactate into pyruvate.
Lactate Regulates Rat Male Germ Cell Function through Reactive Oxygen Species
PLoS ONE, 2014
Besides giving structural support, Sertoli cells regulate the fate of germ cells by supplying a variety of factors. These factors include hormones, several pro-and anti-apoptotic agents and also energetic substrates. Lactate is one of the compounds produced by Sertoli cells, which is utilized as an energetic substrate by germ cells, particularly spermatocytes and spermatids. Beyond its function as an energy source, some studies have proposed a role of lactate in the regulation of gene expression not strictly related to the energetic state of the cells. The general hypothesis that motivated this investigation was that lactate affects male germ cell function, far beyond its well-known role as energetic substrate. To evaluate this hypothesis we investigated: 1) if lactate was able to regulate germ cell gene expression and if reactive oxygen species (ROS) participated in this regulation, 2) if different signal transduction pathways were modified by the production of ROS in response to lactate and 3) possible mechanisms that may be involved in lactate stimulation of ROS production. In order to achieve these goals, cultures of germ cells obtained from male 30-day old rats were exposed to 10 or 20 mM lactate. Increases in lactate dehydrogenase (LDH) C and monocarboxylate transporter (MCT)2 expression, in Akt and p38-MAPK phosphorylation levels and in ROS production were observed. These effects were impaired in the presence of a ROS scavenger. Lactate stimulated ROS production was also inhibited by a LDH inhibitor or a NAD(P)H oxidase (NOX) inhibitor. NOX4 expression was identified in male germ cells. The results obtained herein are consistent with a scenario where lactate, taken up by germ cells, becomes oxidized to pyruvate with the resultant increase in NADH, which is a substrate for NOX4. ROS, products of NOX4 activity, may act as second messengers regulating signal transduction pathways and gene expression.
Biology of Reproduction, 2003
Capacitation is a process that confers fertilizing ability to spermatozoa and this critical event occurs in the development of mammalian spermatozoa during their transit through the female reproductive tract and precedes fertilization. Because spermatozoa are relatively silent in transcription and translation, posttranslational modifications perform the regulatory functions in these cells during capacitation. In this report, we identify a candidate protein, dihydrolipoamide dehydrogenase, which is a post-pyruvate metabolic enzyme, exhibiting tyrosine phosphorylation during hamster spermatozoal capacitation. This is the first report showing dihydrolipoamide dehydrogenase as a phosphoprotein. The cDNA sequence of hamster testes dihydrolipoamide dehydrogenase does not show any variation from the already reported mammalian dihydrolipoamide dehydrogenases. Downregulation of the activity of the hamster spermatozoal enzyme by its specific inhibitor, 5-methoxyindole-2-carboxylic acid, blocks acrosome reaction completely and hyperactivation partially, confirming the role of dihydrolipoamide dehydrogenase in hamster spermatozoal capacitation. We also delineate the temporal involvement of glucose and pyruvate-lactate, showing that the former is required in the earlier stages and the latter for the later stages of hamster spermatozoal capacitation. The essentiality of pyruvate-lactate during hyperactivation and acrosome reaction necessitates the involvement of the post-pyruvate-lactate enzyme, dihydrolipoamide dehydrogenase. acrosome reaction, developmental biology, gamete biology, signal transduction, sperm capacitation 1 K.M. is a recipient of a CSIR fellowship from the Government of India.
Development, Growth and Differentiation, 1983
The rate of I4CO, liberation from ['4C-l]glucose was identical to that from ['4C-6]glucose in spermatids, but more than the latter in spermatogonia. Rotenone (1 pM) completely inhibited '*CO, release from ['4C-l]glucose in spermatids, but decreased it only 30% in spermatogonia. The activity of glucose-6-phosphate dehydrogenase, but not 6-phosphogluconate dehydrogenase, was markedly lower in spermatocytes and spermatids than in spermatogonia. The activities of the glycolytic enzymes, glucosephosphate isomerase, fructose diphosphatase, glyceraldehyde-3-phosphate dehydrogenase and enolase, differed only slightly in spermatids and spermatogonia. It is concluded that the low glucose-6-phosphate dehydrogenase activity may contribute to the low activity of the pentose cycle in spermatocytes and spermatids.
Development, Growth and Differentiation, 1986
Round spermatids (steps 1-8) were isolated from rat testes and the effect of pyruvate on their intracellular ATP level was examined. Results showed that although the spermatids consumed a considerable amounts of pyruvate, this substrate alone did not maintain their ATP level. However, their ATP level was maintained in the presence of both pyruvate and a-ketovalerate or a-ketobutyrate. Maintenance of the ATP level by these substrates was associated with electron trasnport and oxidative phosphorylation. a-Ketoacid inhibited pyruvate reduction to lactate in the lactate dehydrogenase (LDH) reaction, but increased pyruvate oxidation to CO,. The NADH level in spermatids was too low to be detectable, but the NAD level remained unchanged in the presence of pyruvate and a-ketovalerate. These results suggest that pyruvate by itself is not an adequate energy-yielding substrate for spermatids and that a high NADH/NAD ratio may be essential for maintenance of their ATP level.
Metabolic regulation is important for spermatogenesis
Nature reviews. Urology, 2012
Male factor infertility is increasing in developed countries, and several factors linked to lifestyle have been shown to negatively affect spermatogenesis. Sertoli cells are pivotal to spermatogenesis, providing nutritional support to germ cells throughout their development. Sertoli cells display atypical features in their cellular metabolism; they can metabolize various substrates, preferentially glucose, the majority of which is converted to lactate and not oxidized via the tricarboxylic acid cycle. Why Sertoli cells preferentially export lactate for germ cells is not entirely understood. However, lactate is utilized as the main energy substrate by developing germ cells and has an antiapoptotic effect on these cells. Several biochemical mechanisms contribute to the modulation of lactate secretion by Sertoli cells. These include the transport of glucose through the plasma membrane, mediated by glucose transporters; the interconversion of pyruvate to lactate by lactate dehydrogenase...