Rapid mechanisms of glucocorticoid signaling in the Leydig cell

Stress-mediated elevations in circulating glucocorticoid levels lead to corresponding rapid declines in testosterone production by Leydig cells in the testis. In previous studies we have established that glucocorticoids act on Leydig cells directly, through the classic glucocorticoid receptor (GR), and that access to the GR is controlled prior to the GR by a metabolizing pathway mediated by the type 1 isoform of 11beta-hydroxysteroid dehydrogenase (11betaHSD1). This enzyme is bidirectional (with both oxidase and reductase activities) and in the rat testis is exclusively localized in Leydig cells where it is abundantly expressed and may catalyze the oxidative inactivation of glucocorticoids. The predominant reductase direction of 11betaHSD1 activity in liver cells is determined by an enzyme, hexose-6-phosphate dehydrogenase (H6PDH), on the luminal side of the smooth endoplasmic reticulum (SER). Generation of the pyridine nucleotide cofactor NADPH by H6PDH stimulates the reductase direction of 11betaHSD1 resulting in increased levels of active glucocorticoids in liver cells. Unlike liver cells, steroidogenic enzymes including 17beta-hydroxysteroid dehydrogenase 3 (17betaHSD3) forms the coupling with 11betaHSD1. Thus the physiological concentrations of androstenedione serve as a substrate for 17betaHSD3 utilizing NADPH to generate NADP+, which drives 11betaHSD1 in Leydig cells primarily as an oxidase; thus eliminating the adverse effects of glucocorticoids on testosterone production. At the same time 11betaHSD1 generates NADPH which promotes testosterone biosynthesis by stimulating 17betaHSD3 in a cooperative cycle. This enzymatic coupling constitutes a rapid mechanism for modulating glucocorticoid control of testosterone biosynthesis. Under stress conditions, glucocorticoids also have rapid actions to suppress cAMP formation thus to lower testosterone production.     

NADPH generating enzymes in Leydig cells from diabetic rats.

Impaired testosterone biosynthesis in Leydig cells from streptozotocin treated rats is correlated with the reduced activity of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and isocitrate dehydrogenase. The results shown demonstrate that in the diabetic state the activity of these enzymes is reduced by almost 50 to 59% from normal levels. Insulin treatment restored their activities to normal levels. The diminished supply of NADPH in diabetic interstitial tissue is not the unique factor in the control of steroidogenesis, since the availability of large amounts of exogenous NADPH in the incubations of Leydig cell did not reduce the differences in testosterone synthesis observed when compared with normal cells.     

A histochemical study of the circumtesticular Leydig cells of a teiid lizard, Cnemidophorus tigris

Several oxidative enzymes in the testis of the teiid lizard Cnemidophorus tigris were studied histochemically. The cells of the circumtesticular sheath (Leydig cell tunic) are functionally equivalent to Leydig cells of the interstitium on the basis of similar histochemical reactions for the five enzyme systems studied. Both groups of cells were positive for 3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase, NADH diaphorase, NADPH diaphorase, and glucose-6-phosphate dehydrogenase. These results support the hypothesis that the circumtesticular sheath has endocrine function as indicated by its vascularity and its ability to catalyze histochemical reactions involving steroid biosynthesis.     

NADPH production by the pentose phosphate pathway in the zona fasciculata of rat adrenal gland.

Biosynthesis of steroid hormones in the cortex of the adrenal gland takes place in smooth endoplasmic reticulum and mitochondria and requires NADPH. Four enzymes produce NADPH: glucose-6-phosphate dehydrogenase (G6PD), the key regulatory enzyme of the pentose phosphate pathway, phosphogluconate dehydrogenase (PGD), the third enzyme of that pathway, malate dehydrogenase (MDH), and isocitrate dehydrogenase (ICDH). However, the contribution of each enzyme to NADPH production in the cortex of adrenal gland has not been established. Therefore, activity of G6PD, PGD, MDH, and ICDH was localized and quantified in rat adrenocortical tissue using metabolic mapping, image analysis, and electron microscopy. The four enzymes have similar localization patterns in adrenal gland with highest activities in the zona fasciculata of the cortex. G6PD activity was strongest, PGD, MDH, and ICDH activity was approximately 60%, 15%, and 7% of G6PD activity, respectively. The K(m) value of G6PD for glucose-6-phosphate was two times higher than the K(m) value of PGD for phosphogluconate. As a consequence, virtual flux rates through G6PD and PGD are largely similar. It is concluded that G6PD and PGD provide the major part of NADPH in adrenocortical cells. Their activity is localized in the cytoplasm associated with free ribosomes and membranes of the smooth endoplasmic reticulum, indicating that NADPH-demanding processes related to biosynthesis of steroid hormones take place at these sites. Complete inhibition of G6PD by androsterones suggests that there is feedback regulation of steroid hormone biosynthesis via G6PD.     

Some effects of medroxyprogesterone acetate on intermediary metabolism in rat liver.

This study examines the effects of MPA (medroxyprogesterone acetate) on some of the hepatic enzymes of carbohydrate and lipid metabolism in the rat, and compares these with the effects of cortisol and saline. Levels of reduced nicotinamide adenine dinucleotide phosphate (NADPH) were also measured. Intact mature female Wistar rats with average initial weight of 200 gms were injected with MPA (mO mg/kg IM) once a week for 4 weeks and were sacrificed 3 to 5 days after the last injection. Hydrocortisone (Solu-Cortef [R]) 40 mg/kg IM were given to cortisol-treated animals twice daily for 7 days. The animals were sacrificed 2-4 hours after the last dose was given. Normal saline (0.2 mg. IM) was injected in control animals twice a day. The method of Jellinek, Amako, and Willman was used to analyze NADPH. Liver samples were assayed for various enzymatic activities such as phophofructokinase (PFK); pyruvate kinase (PK), glycerol-3-phosphate dehydrogenase (G3PD), "malic" enzyme (ME), and glucose-6-phosphate dehydrogenase (G6PD). The methods of Colowick and Kaplan were used in enzymatic analyses. Lipogenic stimulation by MPA is indicated by increased levels of G3PD and ME, both of which are implicated in lipogenesis, as well as by NADPH. PFK, PK, and G6PD were all unaffected by the MPA regimen, suggesting that elevation of ME and NADPH activities may reflect increased amino acid conservation. The enzymatic pattern of MPA treatment shows lipogenesis and protein conservation, while that of cortisol regimen shows significantly lower levels of ME, G3PD, and PRK.     

Metabolic Coupling Determines the Activity: Comparison of 11β-Hydroxysteroid Dehydrogenase 1 and Its Coupling between Liver Parenchymal Cells and Testicular Leydig Cells

Background

11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) interconverts active 11β-hydroxyl glucocorticoids and inactive 11keto forms. However, its directionality is determined by availability of NADP+/NADPH. In liver cells, 11β-HSD1 behaves as a primary reductase, while in Leydig cells it acts as a primary oxidase. However, the exact mechanism is not clear. The direction of 11β-HSD1 has been proposed to be regulated by hexose-6-phosphate dehydrogenase (H6PDH), which catalyzes glucose-6-phosphate (G6P) to generate NADPH that drives 11β-HSD1 towards reduction.

Methodology

To examine the coupling between 11β-HSD1 and H6PDH, we added G6P to rat and human liver and testis or Leydig cell microsomes, and 11β-HSD1 activity was measured by radiometry.

Results and Conclusions

G6P stimulated 11β-HSD1 reductase activity in rat (3 fold) or human liver (1.5 fold), but not at all in testis. S3483, a G6P transporter inhibitor, reversed the G6P-mediated increases of 11β-HSD1 reductase activity. We compared the extent to which 11β-HSD1 in rat Leydig and liver cells might be coupled to H6PDH. In order to clarify the location of H6PDH within the testis, we used the Leydig cell toxicant ethane dimethanesulfonate (EDS) to selectively deplete Leydig cells. The depletion of Leydig cells eliminated Hsd11b1 (encoding 11β-HSD1) expression but did not affect the expression of H6pd (encoding H6PDH) and Slc37a4 (encoding G6P transporter). H6pd mRNA level and H6PDH activity were barely detectable in purified rat Leydig cells. In conclusion, the availability of H6PDH determines the different direction of 11β-HSD1 in liver and Leydig cells.     

Ontogenesis of oxidative reaction of 17beta-hydroxysteroid dehydrogenase and 11beta-hydroxysteroid dehydrogenase in rat Leydig cells,a histochemical study

The enzyme 17beta-hydroxysteroid dehydrogenase is required for the synthesis and 11beta-hydroxysteroid dehydrogenase for the regulation of androgens in rat Leydig cells. This histochemical study describes ontogenetic changes in distribution and intensity of these enzymes in Leydig cells from postnatal day (pnd) 1-90. Using NAD or NADP as the cofactor, 17beta-hydroxysteroid dehydrogenase (substrate: 5-androstene-3beta,17beta-diol) peaks were observed on pnd 16 for fetal Leydig cells and on pnd 19 and 37 for adult Leydig cells. Between pnd 13 and 25 the fetal cells showed a higher intensity for the 17beta-enzyme than the adult cells; more fetal Leydig cells were stained with NADP, whereas more adult cells were positive with NAD on pnd 13 and 16. A nearly identical distribution of 11beta-hydroxysteroid dehydrogenase (substrate: corticosterone) was observed with NAD or NADP as the cofactor; the reaction was present from pnd 31 onwards, first in a few adult Leydig cells and later in almost all these cells homogeneously. The ontogenetic curves of the two enzymes show an inverse relationship. To conclude: (1) Generally, a stronger reaction for 17beta-hydroxysteroid dehydrogenase is shown with NAD as cofactor than with NADP; using NADP, fetal Leydig cells show a stronger staining than adult Leydig cells. (2) The data possibly support the notion of a new isoform of 11beta-hydroxysteroid dehydrogenase in addition to types 1 and 2.     

Analysis of lines of mice selected for fat content. 1. Correlated responses in the activities of NADPH-generating enzymes

Estimates of the activities (Vmax) of four enzymes that generate the coenzyme NADPH, an absolute requirement for tissue fatty-acid synthesis, and of the concentration of NADP plus NADPH were made in lines of mice differing in fat content. These lines had been selected from the same base population for 20 generations, and 3 high, 3 low replicates and 1 unselected control were used. Analyses were performed on liver and gonadal fat pad (GFP) of males at 5 and 10 weeks of age. In both the liver and the GFP, measurable activities of the four enzymes: glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), isocitrate dehydrogenase (IDH) and malic enzyme (ME) expressed per mg soluble protein were, with minor exceptions, higher in the Fat (F) than in the Lean (L) lines at both ages; the highest ratio being 2.2 for ME in the GFP. The relationships between these measurable activities (Vmax) and in vivo lipogenesis are not however known. When expressed per gram tissue, the ratios for F to L in the GFP were less than 1 in most cases, presumably because of the very different adipocyte numbers and/or sizes between the lines. There were no significant differences between the lines in the concentration of NADP plus NADPH per gram tissue in liver or GFP, suggesting that F lines converted NADP to NADPH faster than L lines. It is predicted that selection on the enzyme activities would be less efficient than direct selection at changing fat content.     

Purification and Characterization of the Main Isozyme of Polyphenol Oxidase in Mung Bean (Vigna mungo) Seedlings

The induction of NADPH-generating enzymes by polychlorinated biphenyls (PCB) in rats was investigated. The administration of PCB to rats for 3 and 14 days increased the activities of malic enzyme (ME, EC 1.1.1.40), glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49), and 6-phosphogluconate dehydrogenase (6PGD, EC 1.1.1.44) about 2-fold above the control level in the liver. Hepatic mRNA levels of ME, G6PD, and 6PGD, except for G6PD mRNA of the 14-day group, were also elevated to the same degree as the enzyme activities in PCB-treated rats. In rats fed a PCB-containing diet for 1 day, the hepatic mRNA levels of ME and G6PD were elevated prior to the induction of enzyme activity. In the kidney, lung, spleen, heart, and testis, the mRNA levels of ME, G6PD, and 6PGD were not affected by PCB. The induction of hepatic NADPH-generating enzymes would imply an increased demand of NADPH in the liver of rats fed with a PCB-containing diet.     

Histochemical studies on the submandibular ganglia of marmosets (Callithrix jacchus and Callithrix penecillata).

The histochemistry of the neural cells was studied in the submandibular ganglia of 5 Callithrix jacchus (3 males and 2 females) and 4 Callithrix penicillata (2 males and 2 females). These cells contain neutral mucopolysaccharides, nucleoproteins and lipidic materia, but are apparently devoid of glycogen. It is impossible to demonstrate in them any reactivity for UDPG-GT, phosphorylases, ATPase at pH 6.3, leucine aminopeptidase and alanyl aminopeptidas. The reaction for the other searched enzymes was as follows: weak (F-1,6-P Ald and cytochrome oxidase), weak to moderate (ADH, 6-P-GDH, ICDH, SDH, MDH, alpha-GPDH and beta-OHBDH), moderate (G-6-PDH, F-1,6-PA, LDH and GDH), moderate to strong (ATPase at pH 7.4, nonspecific esterase and acid phosphatase) and strong (G-6-PA, NADH2,-TR, NADPH2-TR, ATPase at pH 8.5 and 9.4 and alkaline phosphatase).     

Isozymes of Glucose-6-phosphate Dehydrogenase and NAD+-malate Dehydrogenase in Shoot-forming Foliar Discs of Tobacco

Discrete pale, meristematic, shoot-forming zones (SF) and green,relatively nondividing, non-shoot-forming zones (NSF) of cellswere obtained from leaf discs of tobacco cultured for 12 dayson a shoot-forming medium. Higher chlorophyll and starch content,increased rates of O₂ evolution and CO₂ fixation in light, andincreased activities of amylases and chloroplastic enzymes suchas ribulose 1,5-bisphosphate carboxylase and NADP⁺-linked glyceraldehyde-3-phosphatedehydrogenase (G3PDH) were characteristic of the cells constitutingNSF. On the other hand, active participation of sucrose hydrolysis,dark-mediated CO₂ incorporation, an oxidative pentose phosphatepathway, glycolysis and mitochondrial complements in shoot formationwere evident from the significantly high activities of phosphoenolpyruvatecarboxylase, invertase, glucose-6-phosphate dehydrogenase (G6PDH),NAD+-G3PDH and NAD+-linked malate dehydrogenase (NAD+-MDH) respectively,in SF cells. Detection of activity of the enzymes by stainingon polyacrylamide gels disclosed synthesis of additional isoenzyme(s)of G6PDH, NAD+-MDH and peroxidase in shoot initiation sites.The much pronounced activity and isozyme groups of G6PDH andNAD+-MDH in the photosynthetically incompetent shoot-formingcells, are considered to increase the carbon budget of the differentiatingcells through non-autotrohpic CO₂ fixation and to supplementreducing power (NADPH) for the organogenetic process which requiresmuch energy. The changes in isozymes of these enzymes, as inthe isoperoxidase system, probably can serve as useful markersof the differentiation process. (Received January 23, 1981; Accepted June 17, 1981)     

Histology and histochemistry of the testis and ovary of the platyfish,Xiphophorus maculatus,from birth to sexual maturity

Summary The gonads of 3-day- to 7-month-old male and female platyfish (Xiphophorus maculatus) were examined for the presence of 5-3-hydroxysteroid dehydrogenase (3-HSD) and glucose-6-phosphate dehydrogenase (G6PD) by histochemical means. In 3-day-old males a positive response for both enzymes is localized in the Leydig cells. With subsequent testicular development, these cells increase in number and display greater activity at the periphery of the testis and around the efferent ducts. In 3-day-old females 3-HSD and G6PD are localized in the stromal cells of the ovary. These cells increase in number and activity as the animals become sexually mature. Sertoli cells, efferent duct epithelium, and ovarian granulosa cells are negative at all stages of development examined. Our findings suggest that the gonads of neonatal fish possess the potential for steroidogenesis. The role played by sexsteroid hormones in the maturation of the brain-pituitary-gonad axis is discussed.     

Suppression of interleukin-1 beta-induced nitric oxide production in RINm5F cells by inhibition of glucose-6-phosphate dehydrogenase

In rat pancreatic islets and insulin-producing cell lines, IL-1beta induces expression of inducible nitric oxide synthase and NO production leading to impairment of glucose-stimulated insulin release and decreased cell survival. NADPH is an obligatory cosubstrate for iNOS synthesis of NO. We hypothesized that IL-1beta stimulates an increase in activity of NADPH-producing enzyme(s) prior to NO production and that this increase is necessary for NO production. Using rat insulin-secreting RINm5F cells, we found that (1) IL-1beta caused a biphasic change in the NADPH level (increased by 6 h and decreased after prolonged incubation in the presence of 2 ng/mL IL-1beta); (2) IL-1beta stimulated increased activity of glucose-6-phosphate dehydrogenase (G6PD) in a time- and dose-dependent manner, and G6PD expression was increased by about 80% after exposure to 2 ng/mL IL-1beta for 18 h: (3) IL-1beta-stimulated NO production was positively correlated with increased G6PD activity; (4) IL-1beta did not cause any significant change in enzyme activity of another NADPH-producing enzyme, malic enzyme; (5) IL-1beta-induced NO production was significantly reduced either by inhibiting G6PD activity using an inhibitor of G6PD (dehydroepiandrosterone) or by inhibiting G6PD expression using an antisense oligonucleotide to G6PD mRNA; and (6) IL-1beta stimulated a decrease in the cAMP level. 8-Bromo-cAMP caused decreased G6PD activity, and the protein kinase A inhibitor H89 led to a increase in G6PD activity in RINm5F cells. In conclusion, our data show that IL-1beta stimulated G6PD activity and expression level, providing NADPH that is required by iNOS for NO production in RINm5F cells. Also, inhibition of the cAMP-dependent PKA signal pathway is involved in an IL-1beta-stimulated increase in G6PD activity.     

Autoradiographical localization of luteinizing hormone releasing hormone (LHRH) receptors on rat testicular intertubular cells fractionated on Percoll density gradients

The specific binding of 125I-labelled [D-Ser(tBu)6,des-GlyNH2(10)] LHRH ethylamide (LHRH-A) to testicular intertubular cells fractionated on Percoll density gradients was investigated. The greatest binding per cell occurred in the density region which contained the largest proportion of Leydig cells (sp. gr. 1.0820-1.0585). Autoradiographs of the cells from this region confirmed that silver stains were predominantly located over the Leydig cell, significantly (P less than 0.01) more grains were observed over this cell type in the total binding fractions than in the non-specific binding fractions. However, 5.9% of cells other than Leydig cells (testicular macrophages and indeterminate connective tissue cells) from this region also displayed significant displaceable binding (P less than 0.01). The location of [125I]LHRH-A binding to cells in other density regions, which did not contain identifiable Leydig cells, could not be established by autoradiography. These results confirm that the Leydig cell possesses LHRH receptors, but also indicate that other testicular cells have specific, high-affinity binding sites for LHRH-A, and may either be responsive to direct stimulation by LHRH, or may partially mediate the effects of LHRH and its agonists on Leydig cell function.     

Histochemical changes in the Leydig cells of rats drinking the aqueous hollyhock extract

The effect of aqueous hollyhock flower (Althaea rosea Cav. var. nigra) extract on the rat Leydig cell metabolism and morphology was studied using histochemical, morphometric and radioimmunological methods. The rats were drinking the extract for 30 days (group A1) and for 180 days (group A2). Leydig cells of group A1 manifested marked increase in the 3beta-HSD, G6PD and NADPD activities and in the Khanolkar reaction intensity. These findings were accompanied by the increase in the volume of Leydig cells and their nuclei. In group A2 Leydig cells, statistically insignificant changes in the G6PD and NADPD activities were observed, however, the significant increase in the 3beta-HSD activity and the Khanolkar reaction intensity indicated compensatory changes. The statistically significant elevation of the androgen level accompanied by a decrease in estrogen content in homogenates of group A2 testes pointed to weak antiestrogenic effect of the extract. The obtained results indicate an influence of the hollyhock extract on steroid metabolism.     

Possible involvement of NADPH requirement in regulation of Glucose-6-Phosphate and 6-Phosphogluconate dehydrogenase levels in rat liver

Summary Previous studies examining regulation of synthesis of Glucose-6-Phosphate and 6-Phosphogluconate dehydrogenase in rat liver have focussed on the induction of these enzymes by different diets and some hormones. However, the precise mechanism regulating increases in the activities of these enzymes is unknown and the factors involved remain unidentified. Considering that many of these metabolic conditions occur simultaneously with the increase of some NADPH consuming pathway, in particular fatty acid synthesis, we suggest that the activities of Glucose-6-Phosphate and 6-Phosphogluconate dehydrogenase could be regulated through a mechanism involving changes in the NADPH requirement. Here, we have studied the effect of changes in the flux through different NADPH consuming pathways on the NADPH/NADP ratio and on Glucose-6-Phosphate and 6-Phosphogluconate levels. The results show that: i) an increase in consumption of NADPH, caused by activation of fatty acid synthesis or the detoxification system which consumes NADPH, is paralleled by an increase in levels of these enzymes; ii) when increase in consumption of NADPH is prevented, Glucose-6-Phosphate and 6-Phosphogluconate dehydrogenase levels do not change.Abbreviations G6PDH Glucose-6-Phosphate Dehydrogenase - 6PGDH 6-Phosphogluconate Dehydrogenase - ME Malic Enzyme - NF Nitrofurantoin - CumOOH Cumene Hydroperoxide - t-BHP t-Butyl hydroperoxide - BCNU 1,3,-Bis (2-chloroethyl)-1-nitrosourea - GR Glutathione Dehydrogenase - 2-ME 2-Mercaptoethanol - DTT Dithiothreitol - NADP B-Nicotinamide-Adenine Dinucleotide Phosphate - NADPH B-Nicotinamide-Adenine Dinucleotide Phosphate Reduced - EDTA Ethylenediaminetetraacetic Acid - GSH Glutathione Reduced Form - GSSG Glutathione Oxidized Form     

Inactivation of enzymes and an enzyme inhibitor by oxidative modification with chlorinated amines and metal-catalyzed oxidation systems.

Oxidative inactivation of various key enzymes and alpha-1-proteinase inhibitor (alpha-1-PI) was studied by treatment with N-chloramines and the metal-catalyzed oxidation (MCO)-systems ascorbate/Fe(III) and ascorbate/Cu(II). Chlorinated amines completely inhibited alpha-1-PI, fructose-1,6-bis phosphatase (Fru-P2ase) and glyceraldehyde phosphate dehydrogenase (GAPD) at a low molar excess, and glucose-6-phosphate dehydrogenase (G6PD) at a high molar excess, but did not impair beta-N-acetylglucosaminidase (beta-NAG), alkaline phosphatase (AP) or lactate dehydrogenase (LDH). MCO-systems affected the activities of Fru-P2ase, GAPD, AP, LDH and G6PD, but not those of beta-NAG or alpha-1-PI. EDTA prevented inactivation of Fru-P2ase, G6PD and LDH by ascorbate/Cu(II) and of Fru-P2ase by ascorbate/Fe(III) suggesting a site-specific oxidation catalyzed by a protein-bound metal ion. In conclusion, N-chloramines and MCO-systems exhibited different properties with regard to oxidative inactivation, sulfhydryl-enzymes were susceptible to both systems, but other enzymes were only susceptible to one or neither system.     

The role of NADPH in the regulation of glucose-6-phosphate and 6-phosphogluconate dehydrogenases in rat adipose tissue

Summary Previous studies examining the regulation of the synthesis of G6PDH and 6PGDH in rat liver and adipose tissue have focused on the induction of these enzymes by different diets and some hormones. In rat liver these enzymatic activities seem to be regulated by a mechanism involving changes in the NADPH requirements. In this paper we have studied the effect of changes in the flux through different NADPH-consuming pathways on G6PDH and 6PGDH levels in adipose tissue and on the NADPH/NADP ratio. The results show that: I) an increase in the consumption of NADPH, caused by the activation of either fatty acid synthesis or detoxification systems which consume NADPH, is paralleled by an increase in the levels of these enzymes; II) when the increase in consumption of NADPH is prevented, the G6PDH and 6PGDH levels do not change.Abbreviations G6PDH Glucose-6-Phosphate Dehydrogenase - 6PGDH 6-Phosphogluconate Dehydrogenase - GR Glutathione Reductase - ME Malic Enzyme - tBHP t-Butyl Hydroperoxide - NF Nitrofurantoin - CumOOH Cumene Hydroperoxide     

Histochemistry of oxidative enzymes in experimental allergic encephalomyelitis.

The histoenzymic pattern of oxidative enzymes (G3PD, IDH, SD, G6PD,HBD, NADPH: dehydrogenase) was investigated in experimental allergic encephalomyelitis (EAE) produced in rats according to PATERSON [13]. The results obtained lead to following conclusions: (1) The neuroglia, including the white matter oligodendroglia of immunized rats, exhibits increased oxidoreductase activities; (2) The neuroallergic reaction induces some stimulation of the oxidoreductive metabolism of oligoden-droglia; (3) The enzymatic hyperactivity in EAE does not show any relation to the morphological signs of alterations of the myelin sheath.