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-Stimulated Lactate Production Is Linked to Lactate Dehydrogenase A Expression and Activity Increase in Porcine Cultured Sertoli Cells1
INSERM U-407, Communications Cellulaires en Biologie de la Reproduction, Centre Hospitalier Lyon-Sud, Pierre-Benite, France
Address all correspondence and requests for reprints to: Dr. M. Benahmed, INSERM U-407, Communications Cellulaires en Biologie de la Reproduction, Bât 3 B, Centre Hospitalier Lyon-Sud, 69 495 Pierre-Benite, France.
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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(TNF) and the site of action of
the cytokine on lactate production were studied. TNF stimulated in a
time- and dose-dependent manner (with an ED50 of 0.1
nM) Sertoli cell lactate production. Two major sites
involved in TNF action were identified. Firstly, TNF was shown to
increase the uptake of glucose substrate in a time- and dose-dependent
manner. The maximal effect was observed after 24 h of treatment,
with an ED50 of 0.1 nM. Secondly, TNF
increased the activity of lactate dehydrogenase (LDH) A isoform, which
is involved in the conversion of pyruvate into lactate. This increase
in LDH-A activity was detected at 12 h and was maximal after
24 h of treatment with TNF. The stimulatory effect of the
cytokine on the LDH-A isoform was observed with an ED50 of
0.05 nM. Such an increase in LDH-A activity was related to
an increase in LDH-A expression, because TNF stimulated LDH-A
messenger RNA (size, 1.5 kilobases, determined by Northern blotting
analysis). Together, assuming that in the seminiferous tubules, TNF
is produced by spermatids that use lactate for their energetic
metabolism, we suggest that the cytokine may potentially represent a
signal used by germ cells to enhance lactate production in Sertoli
cells through, at least, a redistribution of LDH isoforms in favor of
LDH-A. |
Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Several observations have indicated that lactate may represent a preferential energetic substrate for germ cells (12, 13). Indeed, 1) the inability of germ cells (particularly spermatids) to use glucose for their energetic metabolism, 2) their preference for lactate as an energy source, and 3) the capacity of Sertoli cells to produce high amounts of lactate have generated a concept related to Sertoli cell-germ cell metabolic cooperation, with lactate playing a pivotal role (12, 13, 14). Lactate production in Sertoli cells has been shown to be predominantly under the control of the endocrine system, including FSH (15, 16, 17), insulin (16, 17), and insulin-like growth factor-I (IGF-I) (16, 18), reinforcing the initial concept that Sertoli cells represent nurse cells for germ cells (19).
Although several biochemical steps involved in lactate production, including, at least, glucose substrate uptake, glycolysis, and the conversion of pyruvate to lactate, might represent potential targets for the hormone action, up until now only glucose uptake has been reported to be targeted by the endocrine system in Sertoli cells (16, 17, 18, 20).
However, in the present study, by using, as an experimental
model, cultured immature porcine Sertoli cells, we demonstrate that
lactate production might be under a local (testicular) control in
addition to the endocrine control. Specifically, we show that Sertoli
cell lactate is stimulated by tumor necrosis factor- (TNF), a
cytokine previously reported to be produced by germ cells, particularly
spermatids (21). Additionally, we show that the mechanisms of TNF
action on lactate production are novel in that they involve a
redistribution of lactate dehydrogenase (LDH) isoforms, particularly an
increase in the expression and activity of LDH-A, which is known to
favor the conversion of pyruvate to lactate.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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(SA,
3.9 107 U/mg; 1 U is defined as the amount of TNF that
is required to mediate half-maximal cytotoxicity with L929 and/or WEHJ
164 cells in the presence of actinomycin D) and polyclonal rabbit
antiserum raised against human TNF were generously provided by Dr.
De Waele (Innogenetics, Ghent, Belgium). Porcine LDH-A and rat
glyceraldehyde-3-phosphate dehydrogenase (GAPDH) probes were kindly
provided by Dr. S. S. L. Li (Laboratory of Genetics, Research Triangle
Park, NC) and Dr. J. M. Blanchard (Faculté des Sciences,
Montpellier, France), respectively. Sigma Chemical Co. (St. Louis, MO)
was the source of transferrin, insulin, -tocopherol, HEPES,
deoxyribonuclease type I (DNase), lactate dehydrogenase (from rabbit
muscle), 2-deoxy-D-glucose (2-DOG), and nicotinamide
adenine dinucleotide (NAD). [2,6-3H]2-DOG (17 Ci/mmol)
was purchased from Amersham International (Aylesbury, UK).
Sertoli cell isolation and culture
Isolated Sertoli cells were prepared from immature porcine
testes (2–3 weeks old) by collagenase treatment as previously
described (22). Briefly, decapsulated testes were minced and washed in
DMEM-Ham’s F-12 medium (1:1). After collagenase dissociation (0.5
mg/ml, 90 min, 32 C), cells were washed by centrifugation (200 x
g for 10 min). The resulting pellet was then resuspended,
and after a sedimentation period of 5 min, the sedimented tubules were
recovered and washed three times by gravity in DMEM-F-12 medium. These
tubules were then incubated for 10 min (room temperature) in 20 ml 1
M glycine, 2 mM EDTA, and 20 IU/ml DNase in
Ca2+/Mg2+-free PBS solution, pH 7.2. This
treatment led to the release of contaminating interstitial (Leydig)
cells. The glycine-treated tubules were then washed three times (in
DMEM-F-12 medium) by gravity and incubated in 100 ml DMEM-F-12 medium
containing collagenase (0.5 mg/ml), DNase (0.05 mg/ml), and soybean
trypsin inhibitor (0.05 mg/ml) for 15 min at 32 C. The supernatants
containing the peritubular myoid cell fraction were removed, and the
sedimented tubules were treated again as described above with
collagenase (0.5 mg/ml, 20 min, 32 C) until small clumps resulted.
Clumps were left to settle, and the supernatants were discarded. This
procedure led to a purified Sertoli cell population not contaminated by
Leydig cells or germ cells (for details, see Ref.22) and containing
between 2–5% peritubular myoid cells, as evaluated using desmin and
fibronectin immunostaining (23).
Sertoli cells were plated in Falcon (Los Angeles, CA) 24-multiwell
plates (0.5 x 106 cells/dish) and cultured at 32 C in
a humidified atmosphere of 5% CO2-95% air in DMEM-Ham’s
F-12 medium (1:1) containing 1.2 mg/ml sodium bicarbonate, 15
mM HEPES, and 20 µg/ml gentamicin. This medium was
supplemented with transferrin (5 µg/ml) and -tocopherol (10
µg/ml).
Measurement of lactate production
The amounts of lactate present in Sertoli cell-conditioned
medium were estimated by an enzymatic method (24) using a Kontron
fluorimeter (Kontron Instruments, Zurich, Switzerland) at an excitation
wavelength of 340 nm and emission wavelength of 455 nm. Cell number was
determined using a Coulter counter (Coultronics, Margency, France) once
the cells were removed from the culture dishes in trypsin-EDTA.
Measurement of 2-DOG transport
Glucose transport was studied using the uptake of the labeled
nonmetabolizable glucose analog [2,6-3H]2-DOG as
previously described (17).
Two different protocols were used to characterize the short and long
term effects of TNF on glucose uptake in cultured Sertoli cells.
Cells were cultured in DMEM-F-12 medium from days 0–5 of culture, and
medium was changed every 2 days. For the short term action of the
cytokine on glucose uptake, on day 5, the culture medium of Sertoli
cells was discarded, and cells were washed three times (5 min) with
glucose-free PBS, then incubated at 32 C in 0.3 ml glucose-free PBS
containing [2,6-3H]2-DOG (0.5 µCi/ml) in the absence or
presence of the cytokine for 0.5–2.5 h. At the end of the incubation,
dishes were placed on ice and extensively washed with ice-cold buffer
until no radioactivity was present in the washings. The cells were then
dissolved in 0.5 N sodium hydroxide-0.4% deoxycholate
buffer. Aliquots were taken for liquid scintillation spectrophotometry.
To characterize the long term action of TNF on glucose uptake, on
day 5 of culture, Sertoli cells were preincubated (in DMEM-F-12 medium)
with the cytokine for different times (1–48 h). The cells were washed
three times (5 min) with glucose-free PBS. After a 10-min incubation at
32 C (transport is linear under these conditions) with
[2,6-3H]2-DOG (0.5 µCi/ml), Sertoli cells were washed
rapidly with ice-cold buffer and solubilized by the addition of 0.5
N sodium hydroxide-0.4% deoxycholate buffer. Aliquots of
the solubilized extract were assayed for radioactivity.
All results were corrected for extracellular trapping and passive diffusion of [2,6-3H]2-DOG, both of which were measured in the presence of unlabeled 2-DOG at a 1000-fold higher concentration. The nonspecific radioactivity was lower than 5% of the total radioactivity.
LDH activity measurement
After incubation of Sertoli cells in the absence or presence of
the cytokine, the culture medium was discarded, and the cells were
sonicated (three times, 5 sec each time) in 500 µl 0.9% NaCl and
centrifuged (15,800 x g, 10 min). The supernatant
containing the cell extracts was collected and stored at -70 C for
determination of total LDH activity as well as the different LDH
isozymes after electrophoresis.
Total LDH activity was determined by a spectrophotometric method using the Enzyline LDH-Kit (BioMerieux, Lyon, France). One hundred and fifty microliters of supernatant were used for estimation of the activity of the LDH isoenzyme by measuring the oxidation of NADH at 340 nm using an OPEN 30 (BioMerieux). Extinction was recorded at 340 nm for 2 min. The results were expressed as international units of enzyme activity per 106 cells.
Measurement of the activity of LDH isozymes
An agarose gel electrophoresis system in nondenaturing buffer,
according to the method used in serum test, was adapted to separate
Sertoli cell LDH isozymes (25). LDH isozyme activities were visualized
by nitro blue tetrazolium reduction to formazan (Titan Gel LD-Kit
isozyme procedure, Helena Laboratories, Beaumont, TX). Activity bands
were visualized using lactate and NAD as substrates and phenazine
methosulfate as the final hydrogen acceptor. The different bands were
quantified with an integrating densitometer at 870 nm (Cellosystem 2,
Sebia, Issy-les-Moulineaux, France). LDH isozyme activity was
calculated as a percentage of the total LDH activity and expressed as
milliinternational units.
Analysis of messenger RNA (mRNA) levels
Total RNAs were extracted from Sertoli cells cultured in petri
dishes with TRIzol reagent, a monophasic solution of phenol and
guanidine isothiocyanate. This reagent is an improvement over the
single step RNA isolation developed by Chomczynski and Sacchi (26). The
amount of RNA was estimated by spectrophotometry at 260 nm. About 20
µg total RNAs [denatured for 15 min at 65 C in the presence of 2.2
M formaldehyde, 12.5 M formamide, and 1 x
3-(N-morpholino)propanesulfonic acid (MOPS)] were
electophoresed on a 1.2% agarose-2.2 M formaldehyde gel.
After migration in 0.02 M MOPS running buffer, RNAs were
transferred to nitrocellulose membrane Hybond-C Extra (Amersham) in
10 x SSC (1.5 M NaCl and 0.15 M sodium
citrate) and fixed at 80 C for 2 h. Complementary DNA (cDNA)
probes [LDH-A, 1.5-kilobase (kb) Xho-EcoRI; GAPDH, 1.3-kb
Pst1] were labeled with 40 µCi [-32P] deoxy-CTP
(SA, 109 dpm/µg DNA) using a random primed labeling kit
(Promega, Madison, WI). Labeled probes were separated from free
nucleotides by filtration through a diethylaminoethyl-cellulose column.
After 5 h of prehybridization at 42 C, filters were hybridized
with labeled probe (1–4 x 106 cpm/ml) overnight at
42 C in 50% formamide, 5 x SSPE (0.9 M NaCl, 50
mM sodium phosphate, and 5 mM EDTA, pH 7.4),
5 x Denhardt’s solution (1 g Ficoll, 1 g
polyvinylpyrrolidone, and 1 g BSA/liter), 1% SDS, and 100 µg/ml
herring sperm DNA. Afterward, membranes were washed four times in
2 x SSC-0.1% SDS (20 min at room temperature, followed by 40 min
at 55 C). Filters were exposed to Kodak X-Omat S films (Eastman Kodak,
Rochester, NY) at -70 C for 1–2 days. The intensities of the
autoradiographic bands were estimated by densitometric scanning using
the Bioimage scanner (Millipore, Saint Quentin, France). The data were
expressed as the LDH-A/GAPDH mRNA ratio.
Data analysis
All experimental data are presented as the mean ±
SD of triplicate determinations of three replicate cultures
within each treatment group. All experiments reported here were
repeated at least three times with independent cell preparations. A
representative experiment of each series of experiments is presented.
Statistical significance between groups was determined by Student’s
t test using the StatWorks (Hyden and Son, London, UK)
package on a Macintosh computer (Apple Computer Inc., Cupertino, CA).
Differences are accepted as significant at P <
0.05.
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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on lactate production in cultured Sertoli
cells stimulated lactate accumulation in Sertoli cell culture
medium in a time- and dose-dependent manner (Fig. 1
).
Lactate accumulation in culture medium increased between 6–48 h in
both untreated and TNF-treated Sertoli cells. TNF (20 ng/ml; 1
nM) exerted a stimulatory effect on lactate accumulation at
12 h (P < 0.001), 36 h (P <
0.001), and 48 h (P < 0.001; Fig. 1A). The
stimulating action of TNF on lactate production was dose dependent,
with an ED50 of 0.1 nM. The maximal effect was
observed with 8 ng/ml (0.5 nM; Fig. 1B).
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on glucose uptake in cultured Sertoli cells on glucose uptake was evaluated in
parallel with a positive control, namely insulin. As expected, insulin
(1 µg/ml) enhanced hexose uptake at the different times tested,
whereas under similar experimental conditions, TNF (20 ng/ml; 1
nM) exerted no significant action on glucose uptake (Table 1).
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). Such a time-delayed effect of the cytokine was dose
dependent with, again, an ED50 of 1.8 ng/ml (0.1
nM) and maximal effects observed with 8 ng/ml (0.5
nM; Fig. 2B). The stimulatory effect of TNF on glucose
uptake was no longer observed when Sertoli cells were treated with a
neutralizing antibody, supporting the specificity of TNF action on
glucose uptake (Table 2).
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on LDH activity in cultured Sertoli cells enhanced LDH activity in Sertoli cells after at least 12-h
incubation (P < 0.02) with the cytokine (20 ng/ml; 1
nM; Fig. 3A). The maximal stimulatory effect
was observed after 24 h of treatment (P < 0.001).
Such a stimulatory effect of TNF on LDH activity was dose dependent,
as half-maximal (ED50) and maximal effects were observed
with 2 ng/ml (0.1 nM) and 8 ng/ml (0.5 nM),
respectively (Fig. 3B).
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on LDH activity was no longer observed
when Sertoli cells were treated with a neutralizing antibody,
supporting the specificity of TNF action on LDH activity (Table 3). In control experiments, we confirmed that such a LDH
activity was exclusively detected in Sertoli cells, but not in their
conditioned medium regardless of whether the cells were treated with
the cytokine (data not shown).
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on LDH isozyme distribution on Sertoli cell LDH
activity, the electrophoretic pattern of LDH isozymes in cultured
Sertoli cells was studied in the absence or presence of the cytokine.
LDH isozymes were separated on an agarose slab gel, and their relative
activities were compared as indicated in Materials and
Methods. In the presence of TNF (20 ng/ml; 1 nM;
24 h), the pattern of LDH isozyme activities dramatically changed,
in that the activities of LDH isoforms rich in A subunits, namely
LDH-5(A4) [and, to a lesser extent, LDH-4(A3B1)] were increased (Fig. 4A). The most significant (P < 0.001)
increase (7-fold) after TNF treatment was observed in the activity
of LDH-5(A4) (Fig. 4B).
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on LDH-5(A4) activity increased in a time-dependent manner LDH-A4 activity in
cultured porcine Sertoli cells. Such an increase was significant
(P < 0.002) after 12-h exposure to the cytokine and
was maximal after 24-h exposure (Fig. 5A).
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concentration in the culture medium, and half-maximal
(ED50) and maximal effects were observed at 0.9 ng/ml (0.05
nM) and 11 ng/ml (0.55 nM), respectively (Fig. 5B
). Finally, the stimulatory action of TNF on the LDH-A4 activity
was specific, as it was not observed when TNF-treated Sertoli cells
were incubated in the presence of a neutralizing antibody raised
against TNF (Fig. 6, A and B).
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on LDHA mRNA expression (0.05–50 ng/ml; 2.5 pM to 2.5 nM;
24 h) treatment resulted in a dose-dependent increase in LDH-A
mRNA (1.5 kb). The maximal (P < 0.001) effect of the
cytokine was observed with 3.1 ng/ml (0.2 nM; Fig. 7).
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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on the production of
lactate, a preferential energetic substrate for germ cells. For this
purpose, the experimental model used was purified porcine Sertoli cells
cultured in defined medium. By using this model, in previous reports we
have shown that under similar experimental conditions, the cytokine
regulates Sertoli cell-specific activities without exerting a mitogenic
(27, 28) or a cytotoxic (27) effect on these cells. In the present
study, it is demonstrated that TNF stimulates lactate production
through an increase in glucose uptake and a redistribution of LDH
isoforms, mainly through an increase in the expression and the activity
of LDH-A, which favors the transformation of pyruvate into lactate.
Among the potential steps involved in the production of lactate in
Sertoli cells, the present study has focused on at least two major
steps: the glucose substrate transport into the cell and the LDH
isoenzyme system (which reversibly catalyzes the interconversion of
lactate and pyruvate). With regard to glucose uptake in Sertoli cells,
although various hormones, such as insulin (16, 17), IGF-I (16, 18),
and FSH (16, 17, 18), rapidly stimulate (i.e. in terms of
minutes) glucose uptake, the effects of TNF were observed after a
long term treatment, as the stimulatory action of the cytokine on
glucose uptake was detected at 6 h and was maximal at 24 h.
Such an observation suggests that TNF affects Sertoli cell glucose
transport through different mechanisms. Firstly, it is possible that
the cytokine may use Sertoli cell intermediates to enhance glucose
uptake. Among the potential candidates are different growth factors and
cytokines, including transforming growth factor-ß (TGFß), IGF-I,
and epidermal growth factor (EGF)/TGF. Although TGFß enhances
glucose uptake in Sertoli cells, its effects are time delayed,
i.e. kinetically close, if not similar, to those of TNF
(17), therefore excluding the possibility that it may mediate TNF
action on hexose uptake. By contrast, IGF-I and EGF/TGF appear as
more appropriate intermediates in TNF action on glucose uptake in
Sertoli cells. Indeed, these two factors 1) are produced in Sertoli
cells (for references, see Refs. 9, 10, and 29) and 2) enhance rapidly
(in terms of minutes) glucose uptake (16, 18, 30), probably through
specific receptors identified in Sertoli cells (31, 32). However, our
recent observations indicating that TNF did not affect IGF-I
production and IGF-I receptor mRNA and protein in Sertoli cells (28)
suggest that IGF-I is probably not the appropriate Sertoli cell
intermediate in TNF action on glucose uptake. On the other hand,
although we do not know at the present time whether TNF affects
EGF/TGF expression in Sertoli cells, this cytokine may well increase
EGF/TGF action through an enhancement of EGF receptor, as shown in
different cell types (33), including Sertoli cells (Morera, A. M., and
M. Benahmed, unpublished data). Further studies, however, are required
to confirm the potential involvement of the EGF receptor in the
stimulatory effect of TNF on glucose uptake. Secondly, TNF may
increase glucose uptake through a direct action on Sertoli cell glucose
transporters. Such a hypothesis is mainly supported by several data
reported in extragonadal cells (34, 35, 36), showing that, for example, in
3T3-LI preadipocytes, TNF increased the mRNA for glucose transporter
GLUT I (36), a transporter that has been found in Sertoli cells
(37).
In the present study, we show that the expression and activity of LDH-A
are other potential sites of action of TNF in stimulating lactate
production. Although the stimulatory action of TNF on lactate
production in some cell lines such as L6 myocytes has been shown to be
linked to an increase in glycolysis (through activation of a futile
substrate cycle between fructose-6-phosphate and fructose-1–6
biphosphate) (38), this is, to our knowledge, the first report
indicating that LDH-A is a target for TNF action. Biochemical and
genetic studies of LDH have shown that its isozymes are encoded by
three different genes, ldh a (muscle type), ldh
b (heart type), and ldh c (testicular germ
cell type) (25, 39). The ldh c gene product corresponds to
the homotetrameric LDH C4 isozyme present only in mature testis and
spermatozoa (25). The ldh a and ldh b genes give
rise to various combinations of the LDH-A and LDH-B proteins and
particularly to five tetrameric LDH isozymes, LDH-1 (B4), LDH-2 (A1B3),
LDH-3 (A2B2), LDH-4 (A3B1), and LDH-5 (A4). These five isozymes are
found in various proportions in different somatic tissues, including
Sertoli cells (25). The LDH-5 (A4) isozyme exhibits higher
Km values for pyruvate than lactate (40); an
increase in the activity of such an isozyme after TNF treatment
would, therefore, favor the conversion of pyruvate to lactate. The
TNF-stimulated LDH-5 (A4) and also LDH-4 (A3B1), LDH-3 (A2B2), and
LDH-2 (A1B3) activities may result from an increase in LDH-A subunit
amount and/or activity. The mechanisms involved in such a selective
increase in the activity of LDH-A are yet unknown, and it remains to be
clarified whether the positive effect of TNF on LDH-A mRNA results
form an enhancement of gene transcription and/or mRNA stabilization.
Such a possibility is currently being investigated in our
laboratory.
TNF enhanced lactate production, glucose uptake, and LDH-A
expression and activity in a nanomolar concentration range. Such a
concentration is compatible with the amounts of TNF reported to be
produced in the mouse testis (21) and with the dissociation constant
(Kd) of the TNF receptors detected in porcine
Sertoli cells (27), indicating that TNF action on lactate production
in Sertoli cells might be exerted in a physiological context. Although
some observations indicate that TNF may use the p55 receptor (rather
than the p75 receptor) in porcine (41) and mouse (21) Sertoli cells,
the intracellular transducing pathway involved in the cytokine action
to stimulate lactate production remains to be identified. There is now
a general agreement that TNF, on binding to its receptors, activates
different intracellular signaling pathways including protein kinase C,
protein kinase A, and sphingomyelinase, which results in activation of
the transcription factor nuclear factor-
B (42). In this context, our
present findings coupled to the recent observations of Huang et
al. (43) demonstrating that the activation of protein kinase C and
protein kinase A enhances LDH mRNA levels reinforce the possibility
that the cytokine may use these intracellular transducing systems to
increase the LDH-A expression reported in the present study. We are
investigating such a possibility.
Finally, although there are now several reports indicating that in
addition to the endocrine control, Sertoli cell activity is also
regulated by germ cells such as spermatids (for references, see Refs.
2, 44, and 45), the germ cell signaling molecules involved in such a
control of Sertoli cells remain largely unknown. Our present findings,
demonstrating that TNF (produced in spermatids) (21) stimulates
lactate production in Sertoli cells make this cytokine a good candidate
for involvement in the control exerted by germ cells on Sertoli cell
activity. Furthermore, that Sertoli cell lactate production is under
both the endocrine (FSH and IGF-I) and local control raises the
question of whether the actions of two systems might be additive,
synergistic, or antagonistic. Recent observations from our laboratory
indicating that TNF antagonizes both FSH (27) and IGF-I (28) action
in cultured Sertoli cells suggest that probably in the adult gonad, the
local control may well be the predominant one. More specifically, it is
possible that spermatids at particular stages of the seminiferous
epithelium cycle control and direct, via the cytokine, glucose
metabolism in the Sertoli cell toward the formation of lactate, a
metabolite that they use as a preferential energetic substrate. Such a
potential local and stage-specific control of lactate is probably more
appropriate than the systemic (endocrine) control, in that it better
takes into account the specific germ cell metabolic requirements.
In conclusion, by using porcine cultured Sertoli cells as a model, we
report that TNF stimulates lactate production, probably through an
increase in LDH-A expression and activity. Assuming that the cytokine
originates from spermatids that prefer lactate as an energy substrate,
it is suggested that TNF may represent one of the signaling
molecules involved in germ cell-Sertoli cell metabolic cooperation.
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Acknowledgments |
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Footnotes |
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Received August 13, 1996.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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in mouse
spermatogenic cells. Endocrinology 133:389–396[Abstract]
antagonizes follicle-stimulating hormone action in cultured Sertoli
cells. Endocrinology 133:69–76[Abstract]
stimulates IGF binding
protein 3 expression in cultured porcine Sertoli cells. Endocrinology 137:296–303[Abstract]
and their receptors
during post-natal development and spermatogenesis of the boar testis.
Mol Cell Endocrinol 123:61–69[CrossRef][Medline]
. J Biol Chem 265:20506–20516-induced glucose transporter (Glut 1) mRNA
stabilization in 3T3–L1 preadipocytes. J Biol Chem 267:8336–8341 receptor p55 is under hormonal
(follicle-stimulating hormone) control in testicular Sertoli cells.
Biochem Biophys Res Commun 224:631–637[CrossRef][Medline]
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R.;a. Grataroli, F. Boussouar, and M. Benahmed Role of Sphingosine in the Tumor Necrosis Factor {alpha} Stimulatory Effect on Lactate Dehydrogenase A Expression and Activity in Porcine Sertoli Cells Biol Reprod, November 1, 2000; 63(5): 1473 - 1481. [Abstract] [Full Text]
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F. Boussouar and M. Benahmed Epidermal Growth Factor Regulates Glucose Metabolism Through Lactate Dehydrogenase A Messenger Ribonucleic Acid Expression in Cultured Porcine Sertoli Cells Biol Reprod, October 1, 1999; 61(4): 1139 - 1145. [Abstract] [Full Text]
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 F. Boussouar, R. Grataroli, J. Ji, and M. Benahmed Tumor Necrosis Factor-{alpha} Stimulates Lactate Dehydrogenase A Expression in Porcine Cultured Sertoli Cells: Mechanisms of Action Endocrinology, July 1, 1999; 140(7): 3054 - 3062. [Abstract] [Full Text]
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 F. Delfino and W. H. Walker Stage-Specific Nuclear Expression of NF-{kappa}B in Mammalian Testis Mol. Endocrinol., November 1, 1998; 12(11): 1696 - 1707. [Abstract] [Full Text]
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