Search

Sertoli cells provide structural and nutritional support for germ cell development. They actively metabolize glucose and convert it into lactate, which is an important source of energy for germ cells. They also oxidize fatty acids (FA), stored as triacylglycerides (TAGs) within lipid droplets (LD), to fulfill their own energy requirements. So, the combined regulation of lactate production and FA metabolism may be relevant to the physiology of seminiferous tubules. Resveratrol (RSV) is a nutritional supplement found primarily in red grape skin that exhibits multiple beneficial health effects: it is cardioprotective, anti-inflammatory, anticancer, and antiaging. The aim of this study was to evaluate the effect of RSV in Sertoli cells lactate production and lipid metabolism. Sertoli cell cultures obtained from 20-day-old rats were incubated for different times with 10 or 50 μM RSV. RSV treatment increased lactate production and glucose consumption. These increments were accompanied by a rise in GLUT1 expression, which is the main glucose transporter in Sertoli cells. On the other hand, RSV decreased LD content and TAG levels. In addition, an increase in ATGL and FAT/CD36 mRNA levels was observed, which suggests augmented cytoplasmatic FA availability. RSV treatment also increased P-ACC levels, which might indicate that RSV promotes FA transport into the mitochondria to be oxidized. An enhanced expression of LCAD and MCAD, enzymes that participate in the oxidation of FA, was also observed. Altogether, these results suggest that RSV simultaneously regulates Sertoli cells lactate production and lipid metabolism, ensuring an adequate energetic balance both in germ and Sertoli cells., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Sertoli cells provide the structural and nutritional support for germ cell development; they actively metabolize glucose and convert it to lactate, which is an important source of energy for germ cells. Furthermore, Sertoli cells can oxidize fatty acids, a metabolic process that is assumed to fulfill their own energy requirements. Fatty acids are stored as triacylglycerides within lipid droplets. The regulation of fatty acid storage in conjunction with the regulation of lactate production may thus be relevant to seminiferous tubule physiology. Our aim is to evaluate a possible means of regulation by the PPARγ activation of lipid droplet formation and lactate production. Sertoli cell cultures obtained from 20-day-old rats were incubated with Rosiglitazone (10 μM), a PPARγ activator, for various periods of time (6, 12, 24 and 48 h). Increased triacylglycerides levels and lipid droplet content were observed, accompanied by a rise in the expression of genes for proteins involved in fatty acid storage, such as the fatty acid transporter Cd36, glycerol-3-phosphate-acyltransferases 1 and 3, diacylglycerol acyltransferase 1 and perilipins 1, 2 and 3, all proteins that participate in lipid droplet formation and stabilization. However, PPARγ activation increased lactate production, accompanied by an augmentation in glucose uptake and Glut2 expression. These results taken together suggest that PPARγ activation in Sertoli cells participates in the regulation of lipid storage and lactate production thereby ensuring simultaneously the energetic metabolism for the Sertoli and germ cells.

The purpose of this study was to evaluate the existence of a possible simultaneous regulation of fatty acid (FA) metabolism and lactate production by PPAR α and PPAR β/δ activation in Sertoli cells (SC). SC cultures obtained from 20-day-old rats were incubated with WY14643 or GW0742-pharmacological activators of PPAR α and PPAR β/δ respectively. The fatty acid transporter CD36, carnitine palmitoyltransferase 1, long- and medium-chain 3-hydroxyacyl-CoA dehydrogenases mRNA levels were analyzed. An increase in the above-mentioned genes in response to activation of both nuclear receptors was observed. Additionally, PPAR β/δ activation increased lactate production as a consequence of increased pyruvate availability by inhibiting the Pyruvate Dehydrogenase Complex. Altogether, these results suggest that in SC, PPAR α activation participates in the regulation of FA metabolism. On the other hand, PPAR β/δ activation regulates FA metabolism and lactate production ensuring simultaneously the energetic metabolism for SC and germ cells., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background and Aim: Basic fibroblast growth factor (bFGF) and interleukin 1β (IL1β) belong to the set of intratesticular regulators that provide for the fine-tuning of processes implicated in the maintenance of spermatogenesis. The aim of this study was to investigate if bFGF and IL1β activate CREB, what signaling pathways may be participating and the possible relationship between CREB activation and the regulation of Sertoli cell function., Methods: Twenty-day-old rat Sertoli cell cultures were used., Results: Cultures stimulated with bFGF and IL1β produced a time-dependent increment in phosphorylated CREB levels that reached maximal values in 5- and 15-minute incubations respectively. MEK inhibitors--PD98059 and U0126--blocked the effect of bFGF on phosphorylated CREB while a p38-MAPK inhibitor--SB203580--blocked the effect of IL1β on phosphorylated CREB. A possible correlation between CREB regulation and two Sertoli cell-differentiated functions, Ldh A and transferrin expression, was explored. PD98059 blocked the ability of bFGF to stimulate Ldh A expression and SB203580 blocked the ability of IL1β to stimulate Ldh A expression and LDH activity. Concerning transferrin, PD98059 and U0126 were able to inhibit the ability of bFGF to stimulate its secre tion. On the contrary, SB203580 was unable to block IL1β induced increase in transferrin secretion suggesting that the p38-MAPK pathway does not participate in the mechanism of action of the cytokine to regulate transferrin., Conclusions: The results presented herein suggest that CREB is stimulated in response to bFGF and IL1β through p42/p44-MAPK and p38-MAPK pathways and that this transcription factor may be partially responsible for the regulation of Sertoli cell function.

This work evaluates adenosine effects on Sertoli cell functions, which are different to those resulting from occupancy of purinergic receptors. The effects of adenosine and N(6)-cyclohexyladenosine (CHA) - an A(1) receptor agonist resistant to cellular uptake - on Sertoli cell physiology were compared. Adenosine but not CHA increased lactate production, glucose uptake, GLUT1, LDHA and MCT4 mRNA levels, and stabilized ZO-1 protein at the cell membrane. These differential effects suggested a mechanism of action of adenosine that cannot be solely explained by occupancy of type A(1) purinergic receptors. Activation by adenosine but not by CHA of AMPK was observed. AMPK participation in lactate production and ZO-1 stabilization was confirmed by utilizing specific inhibitors. Altogether, these results suggest that activation of AMPK by adenosine promotes lactate offer to germ cells and cooperates in the maintenance of junctional complex integrity, thus contributing to the preservation of an optimum microenvironment for a successful spermatogenesis., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The gonadotropin FSH plays a key role in the control of Sertoli cell function. The FSH molecular mechanism of action is best recognized for its stimulation of the adenylyl cyclase/cAMP pathway. However, other signaling events have also been demonstrated in Sertoli cells. We have recently presented evidence that FSH can stimulate the phosphatidylinositol 3-kinase/protein kinase B (PI3K/PKB) pathway in 20-day-old Sertoli cells. At the same time, it was proposed that in 8-day-old Sertoli cells the effects of FSH on phosphorylated PKB (P-PKB) levels can be explained by a combination of increased secretion of endogenous IGF-I, decreased IGF-binding protein-3 (IGFBP-3) production, and a synergistic action of FSH on IGF-I-dependent PI3K activation. The aim of the present study was to determine whether the effect of FSH on 20-day-old Sertoli cells is mediated by IGF-I secretion. Twenty-day-old rat Sertoli cell cultures were used. FSH stimulation produced a time-dependent increment in P-PKB levels reaching maximal values in 60-min incubations. IGF-I stimulation was also time-dependent reaching maximal values in 15-min incubations. On the other hand, stimulation of the cultures with FSH showed time-dependent inhibition in phosphorylated mitogen-activated protein kinase (P-MAPK) levels. In sharp contrast, stimulation of the cultures with IGF-I showed time-dependent increments in P-MAPK levels reaching maximal stimulus in 15-min incubations. In order to rule out an IGF-I action on FSH stimulation of P-PKB levels, the effect of a specific IGF-I antibody on the ability of both hormones to increase P-PKB levels was evaluated. As expected, the antibody inhibited IGF-I stimulation of P-PKB levels. However, simultaneous addition of an IGF-I antibody with FSH did not modify the ability of the hormone to increase P-PKB levels. The next set of experiments intended to analyze the relevance of a PI3K/PKB pathway to two biological responses of Sertoli cells to FSH and IGF-I. The PI3K inhibitor, wortmannin, dose-dependently decreased FSH-stimulated lactate and transferrin production. On the other hand, wortmannin was not able to modify the ability of IGF-I to stimulate these metabolic events. In addition, the analysis of the participation of a MAPK pathway in IGF-I regulation of Sertoli cell biological responses showed that the MAPK kinase inhibitors, PD98059 and U0126, decreased IGF-I-stimulated transferrin secretion while not modifying IGF-I-stimulated lactate levels. In summary, results obtained so far support the hypothesis that FSH action on P-PKB levels and Sertoli cell metabolism in 20-day-old animals is not mediated by autocrine regulation of an IGF-I/ IGFBP-3 axis as previously proposed in 8-day-old Sertoli cells.

Basic fibroblast growth factor (bFGF) belongs to the large set of intratesticular regulators that provide the fine tuning of cellular processes implicated in the maintenance of spermatogenesis. The aim of the present study was to determine the participation of mitogen-activated protein kinase (MAPK) and phosphatidyl inositol 3-kinase/protein kinase B (PI3K/PKB) pathways in bFGF regulation of Sertoli cell function. Twenty-day-old rat Sertoli cell cultures were used. Stimulation of the cultures with bFGF showed a time-dependent increment in phosphorylated MAPK and PKB levels that reached maximal values in 5-min incubations. MAPK kinase inhibitors U0126 (U) and PD98059 (PD) and a PI3K inhibitor wortmannin (W) were able to block the stimulatory effects of bFGF on phosphorylated MAPK and PKB levels respectively. The participation of MAPK- and PI3K/PKB-signaling pathways in the regulation by bFGF of two well-known Sertoli cell-differentiated functions, lactate and transferrin production, was next explored. As for lactate production, PD and W did not modify the ability of bFGF to stimulate lactate production. However, a combination of PD and W partially impaired the increase in lactate production elicited by bFGF. The participation of MAPK- and PI3K/PKB-signaling pathways in the regulation by bFGF of glucose uptake and lactate dehydrogenase (LDH) activity was also analysed. In this respect, it was observed that W markedly decreased basal and bFGF-stimulated glucose uptake and that U and PD did not modify it. On the other hand, U and PD decreased the stimulation of LDH activity by bFGF whereas W did not modify it. As for transferrin production, while both MAPK kinase inhibitors partially decreased the ability of bFGF to stimulate transferrin secretion, the PI3K inhibitor did not modify it. In summary, the results demonstrated that bFGF stimulates MAPK- and PI3K/PKB-dependent pathways in rat Sertoli cells. Moreover, these results showed that while bFGF utilizes the MAPK pathway to regulate transferrin production and LDH activity, it uses the PI3K/PKB pathway to regulate glucose transport into the cell.

The FSH molecular mechanism of action is best recognized for its stimulation of the adenylyl cyclase/cAMP pathway via activation of a G protein. Recently, links between cAMP, phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB) signaling pathways in thyroid and granulosa cells have been observed. The aim of this study was to investigate the possible role of the PI3K/PKB pathway in FSH regulation of Sertoli cell function. Twenty-day-old rat Sertoli cell cultures were used. An increase in phosphorylated PKB (P-PKB) levels in response to FSH and dibutyryl-cAMP was observed. These increments in P-PKB levels were not observed in the presence of two PI3K inhibitors, wortmannin and Ly 294002. Inhibition of protein kinase A (PKA) by H89 did not decrease FSH stimulation of P-PKB levels. Taken together, these results indicate that FSH increases P-PKB levels in a PI3K-dependent and PKA-independent manner in rat Sertoli cells. In addition, wortmannin partially inhibited the ability of FSH to stimulate two well-known parameters of Sertoli cell function - transferrin secretion and lactate production - at doses equal to or lower than 0.1 microM. Related to lactate production, a decrease in FSH stimulation of lactate dehydrogenase activity and of basal and FSH-stimulated glucose uptake was observed in the presence of wortmannin. These metabolic changes were in most cases accompanied by changes in the levels of P-PKB. Altogether, these results suggest a meaningful role of the PI3K/PKB pathway in the mechanism of action of FSH in rat Sertoli cells.

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 dose-dependent 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 microg/microg 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./microg 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/microg 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.

One of the "nurse cell" functions of Sertoli cells is to provide lactate for the energy production in spermatocytes and spermatids. The present study shows that, as in porcine Sertoli cells, interleukin (IL)1beta and follicle-stimulating hormone (FSH) increase lactate production in rat Sertoli cells (basal, 9.1 +/- 1.0; FSH (100 ng/ml), 16.6 +/- 2.0; IL1beta (50 ng/ml), 13.3 +/- 1.6 microg/microg DNA). Increments in glucose uptake (basal, 1083 +/- 70; FSH, 2686 +/- 128; IL1beta, 1899 +/- 74 dpm/microg DNA), lactic dehydrogenase (LDH) activity (basal, 36.6 +/- 4.1; FSH, 52.2 +/- 4.9; IL1beta, 55.3 +/- 5.1 mUI/microg DNA), LDH A mRNA levels, and redistribution of LDH isozymes are involved in these stimulatory effects. Differences in the period required by IL1beta to increase glucose uptake, as compared with the porcine model, have been observed. In addition, tumor necrosis factor alpha (TNFalpha), one of the major stimulators for lactate production in porcine Sertoli cells, does not control the secretion of this glucose metabolite in rat Sertoli cells. Lactate production may be regulated differently among mammals., (Copyright 2001 Academic Press.)

Sertoli cells are under the control of FSH and androgens and also respond to polypeptidic factors locally produced. Basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) have been proposed to belong to the large set of intratesticular regulators. The aim of the present investigation was to analyze the effects of bFGF and NGF on lactate production, gamma-glutamyl transpeptidase (gamma-GTP) and aromatase activities. Cultured Sertoli cells dose-dependently responded to bFGF by increasing lactate production and gamma-GTP activity under basal conditions. In FSH-stimulated cultures, a synergistic effect of FSH with bFGF for lactate production was observed. NGF did not produce changes in lactate production or gamma-GTP activity at any dose tested. Both peptides decreased FSH-stimulated aromatase activity. These results provide additional evidence for the participation of bFGF and NGF in the complex network of intratesticular regulators. bFGF has pleiotropic effects on Sertoli cell function while the actions of NGF seem to be more limited.

In the present study, a possible role of ceramide in the regulation of Sertoli cell function was investigated. Intracellular ceramide levels were increased by adding N-acetylsphingosine (C2) or by inhibiting ceramidase with (1 S,2R)-D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol (MAPP). Cultured Sertoli cells were stimulated for 3 days with different doses of C2, MAPP, and their corresponding inactive analogs. The effect of these drugs was evaluated along four well-known Sertoli cell parameters: lactate and transferrin secretion, gamma-glutamyl transpeptidase (gamma-GTP) activity, and estradiol production. C2 and MAPP increased lactate production and decreased transferrin secretion. The inactive analogs did not produce any effect. In FSH (follicle-stimulating hormone)-stimulated cultures, C2 and MAPP produced a further increment in lactate production and decreased FSH-stimulated transferrin secretion. No effect was observed under basal or FSH-stimulated gamma-GTP activity, and both treatments decreased estradiol production in response to FSH. Results obtained in dbcAMP (dibutyryladenosine 3':5'-cyclic monophosphate)-stimulated cultures suggest that the observed effects of ceramide on transferrin secretion are secondary to a decrease in cAMP production, whereas the effects of ceramide on lactate and estradiol productions are post-cAMP formation regulatory events. In summary, our results show that ceramide can regulate Sertoli cell function. Similar to what has been observed for other signaling molecules, ceramide can interact with the FSH-dependent pathway, but the precise steps involved in this interaction are still unknown.

To study the role of extracellular nucleosides and nucleotides in the regulation of Sertoli cells, the effects of agonists which occupy A1 and P2 purinergic receptors on aromatase and gamma-glutamyl transpeptidase (gamma-GTP) activities and on transferrin secretion were tested. Sertoli cell treatment with purinergic agonists for a prolonged period of time (72 h) resulted in an increase in aromatase activity under basal conditions. In cultures stimulated with FSH, purinergic agonists counteracted the inhibitory effect on aromatase activity that long-term treatment with FSH promoted. The effects of prolonged treatments with purinergic agonists on the other two parameters of Sertoli cell function were less pronounced. Neither gamma-GTP activity nor transferrin secretion was modified under basal conditions. On the other hand, under conditions where cell differentiation was favored by FSH treatment, reductions in gamma-GTP activity and transferrin secretion were usually observed. The results obtained in dbcAMP-stimulated cultures suggested that A1 agonists exert their regulatory function at the level of cAMP formation while P2 agonists act at a more distal point. The fact that morphological changes induced by FSH were reversed by both types of agonists, while those induced by dbcAMP were only abrogated by P2 agonists, supports this hypothesis. In summary, these results demonstrate that purinergic agonists may be important in the regulation of Sertoli cell function.

gamma-Glutamyl transpeptidase (gamma-GTP) activity in Sertoli cells can be stimulated by FSH. This cAMP-dependent metabolic event can be enhanced when Sertoli cells are co-cultured with germ cells, suggesting that different signal transduction pathways may be involved in the regulation of gamma-GTP activity. In this study we examined the participation of Ca(2+)- and protein kinase C (pkC)-dependent signal transduction pathways in the regulation of basal and FSH-stimulated gamma-GTP activity. Under basal conditions, the increase in extracellular Ca2+ concentration or the addition of the Ca2+ ionophore 4Br-A23187 produced a decrease in gamma-GTP activity. Conversely, blockage of voltage-dependent Ca2+ channels with verapamil or nifedipine or inhibition of Ca(2+)-calmodulin dependent processes with trifluoperazine resulted in an increase in gamma-GTP activity. To study the role of a pkC-dependent pathway the effects of low doses of staurosporine were evaluated. Under these experimental conditions an increase in gamma-GTP activity was observed. It was then investigated whether these signal transduction pathways could interact with the FSH-stimulated cAMP-dependent pathway to regulate gamma-GTP activity. Increase in extracellular Ca2+ concentration, the addition of 4Br-A23187 or the blockage of voltage-dependent Ca2+ channels did not modify FSH-stimulated gamma-GTP activity. However, staurosporine produced an additional increase in FSH-stimulated gamma-GTP activity and this effect was also observed when cells were stimulated with dbcAMP. In summary, our data are consistent with an inhibitory role of Ca(2+)-calmodulin- and pkC-dependent pathways in the regulation of basal gamma-GTP activity. Similar to what has been shown for other Sertoli cell parameters, a pkC-dependent pathway can interact with the FSH-stimulated cAMP-dependent pathway. The precise steps involved in this interaction are still unknown.

Recent observations indicate that Sertoli cell aromatase activity decreases when cultures are performed at high density. Increasing cell density modifies cell shape in culture from flat cells with visible anchorage sites and abundant intercellular spaces to cells with higher profiles that form a uniform epithelial sheet with no intercellular spaces. Changes in cell architecture are associated with reorganization of the cytoskeleton components. In this report, we have tested whether disruption of microfilaments and microtubules by cytochalasin B and colchicine, respectively, has any effect on the ability of FSH to stimulate aromatase activity. Cytochalasin B, but not colchicine, significantly enhanced aromatase activity in FSH and dbcAMP stimulated cells. The increase in aromatase activity was accompanied by a striking change in cell morphology. Time course studies suggested that microfilament organization is involved in some metabolic event which occurs sometime between 2 and 4 h after the initial steps of FSH action. The reversibility of the biochemical and morphological changes induced by cytochalasin B was demonstrated. The effect of cytochalasin B was observed in high but not in low-density cultures, suggesting that microfilament organization in high-density cultures constrains FSH stimulation of aromatase activity. The last two observations made suggest the existence of a dynamic interplay between microfilament organization and FSH action in Sertoli cells.

Sertoli cell aromatase activity is high in very young animals and declines throughout pubertal development. Little is known about the regulatory factors which might be involved in the pronounced decline suffered by this enzymatic activity. In this paper we show that estradiol production in Sertoli cells is dependent on cell density in the culture and that chronic stimulation with hormones can decrease estradiol acute response to FSH. In 8-day-old Sertoli cells cultured at low density (LD: 7.1 +/- 0.3 micrograms DNA), estradiol production was 151 +/- 11 pgE2/micrograms DNA, while in those cultured at high density (HD: 30.3 +/- 0.6 micrograms DNA), production was 30 +/- 5 pgE2/micrograms DNA. Similar results were obtained in 20-day-old Sertoli cell cultures (LD: 57 +/- 4 pgE2/micrograms DNA vs HD: 26.0 +/- 0.6 pgE2/micrograms DNA). On the other hand, treatment of Sertoli cell cultures (8- and 20-day-old) for 96 h, with FSH (100 ng/ml), EGF (50 ng/ml), insulin (10 micrograms/ml) and IGF-I (50 ng/ml) at different densities resulted mostly in inhibition of aromatase activity. The effect caused by FSH was apparently not related to desensitization as aromatization with dbcAMP could not overcome the decreased ability of these cells to produce estradiol. The effect caused by EGF was observed in 8-day-old Sertoli cells cultured under high density conditions. Marked inhibition was observed with insulin and IGF-I in 8-day-old Sertoli cell cultures. Considering previous reports indicating a decrease in Sertoli cell aromatase activity with age, our results suggest a potential role for FSH, EGF, insulin and IGF-I on the Sertoli cell differentiation process which occurs throughout pubertal development.

The hormonal regulation of gamma-glutamyl transpeptidase (gamma-GTP), an enzyme marker of Sertoli cells, was studied in immature rats that received 50 micrograms/day of testosterone propionate (TP) during 6 days to suppress pituitary LH and FSH. Suppression of LH was monitored indirectly by the determination of intratesticular levels of testosterone and suppression of FSH by radioimmunoassay of serum FSH. Enzyme activity in the testis decreased in parallel to intratesticular testosterone suppression, and it did recover up to control values when animals received 500 micrograms/day of TP, a dose that was able to maintain intratesticular testosterone at normal levels. beta-glucuronidase, another enzyme marker of Sertoli cells, was not affected by these treatments. A significant decrease in gamma-GTP was detected 24h after significant suppression of intratesticular testosterone and it returned to control levels 2 days after increasing the dose of TP to 500 micrograms/day. Administration of FSH to rats with depletion of intratesticular testosterone was able to maintain testicular gamma-GTP at control levels. An stimulatory action of FSH could also be demonstrated in primary Sertoli cell cultures. It is concluded that testicular gamma-GTP is under the regulation of both androgens and FSH while beta-glucuronidase is not. Eventhough the function of gamma-GTP in the testis is not known, the key role that it plays in other tissues suggests that it might be important in the regulation of Sertoli cell-germ cell interactions.