Orally administered melatonin stimulates the 3α/β-hydroxysteroid oxidoreductase but not the 5α-reductase in the ventral prostate and seminal vesicles of pinealectomized rats

Summary Pinealectomized rats were treated orally with melatonin (MEL) for 14 days. Prostates and seminal vesicles were investigated for the activity of the 4-3-ketosteroid-5-oxidoreductase (5-R) and of the 3/-hydroxysteroid-oxidoreductase (3-HSO). The activity of the 3a-HSO was significantly stimulated (p<0.01, Friedman test) when compared to controls. The activity of the 5-R did not change significantly.This work was supported by the Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 34 (Endokrinologie).     

The benzilic acid rearrangement of 3α,17β-Diacetoxy-11-hydroxy-12-oxo-5β-androst-9(11)-ene

Zusammenfassung Die Bildung von 11-Carboxy-3, 11, 17-trihydroxy-13-C-nor-5-androstan 11a,17-Lakton aus 3, 17-Diacetoxy-11-hydroxy-12-oxo-5-⁹(11)-androsten wird beschrieben. Der Mechanismus und die Stereochemie dieser Umwandlung (Retro-Aldolkondensation und Benzilsäureumlagerung) wird diskutiert.     

Über die Brenzkatechinamine im Froschherzen und in der Froschhaut vor und nach Verabfolgung von α-Methyldopa

Summary (1) The adrenalin of the frog heart was found to be localized mainly in the granular fraction (100,000g). After pretreatment with -methyldopa (-MD), the heart also contained -methyldopamine, -methylnoradrenalin, and -methyladrenalin. (2) -MD caused a maximal expansion of the melanophores. This action was counteracted byl-dopa, which per se caused a contraction of the melanophores. After pretreatment with -MD the skin contained besides adrenalin also -methyldopamine and -methyladrenalin. In addition also 5-hydroxytryptophan expanded the melanophores.     

Single amino acid substitutions insn-glycerol-3-phosphate dehydrogenase allozymes fromDrosophila virilis

Summary The amino acid sequence was compared among the three allelic variants (allozymes) ofsn-glycerol-3-phosphate dehydrogenase inD. virilis, which are detected by one-dimensional electrophoresis. The GPDH^f variant was different from the GPDH^m by only one substitution of 68-lysine for asparagine; GPDH^s differed from GPDH^m by substitution of 127-glycine for arginine. No electrophoretically silent substitutions were found in a total of 352 amino acid residues.     

Hydra vulgaris ω10-lipoxygenase is used in vivo to synthesize new α-linolenic acid metabolites

Previous studies conducted in cytosolic extracts of the freshwater hydrozoanHydra vulgaris led to the finding of an abundant 11(R)-lipoxygenase catalyzing the peroxidation of polyunsaturated fatty acid (PUFAs) on the tenth carbon atom from the aliphatic end (10 peroxidation). Here we describe experiments aimed at identifying the actual metabolites generated in vivo by such enzymic activity. Homogenates ofH. vulgaris polyps were analyzed by HPLC. This showed the presence of three major components chromatographically identical to three metabolites obtained when incubating the homogenates with exogenous -linolenic acid (-LA). The presence, in extracts of polyps prelabelled with [¹⁴C]--linolenic acid, of radioactive metabolites displaying the same chromatographic properties, substantiated the hypothesis that the natural products isolated in vivo are derived from -LA. Gas chromatographic analyses revealed that this was the most abundant PUFA in both free and phosphoglyceride-bound fatty acid pools. [¹H]-NMR analysis of the endogenous substances, carried out in comparison with products obtained from exogenously incubated -LA, indicated that their structures were those of 9-hydroxy-, 9-hydroperoxy- and 9-keto-octadeca-10E-12Z-15Z-trienoic acids (9--HOTrE,-HPOTrE and-KOTrE).Hydra homogenates transformed 9--HPOTrE partly into 9--HOTrE and partly into 9--KOTrE. Chiral phase HPLC conducted on 9--HOTrE established that this metabolite was composed mostly of theR anantiomer. These observations, and the finding that the presence of exogenous arachidonic acid in incubated homogenates significantly reduces the production of -LA metabolites, provide strong evidence that these compounds are produced by an enzymic activity identical to the previously-describedH. vulgaris (R)-10-lipoxygenase. Further experiments suggested that -LA, acting as the native substrate for this enzyme, is mainly esterified on the 2 position ofHydra phosphoglycerides, and that the production of the -LA metabolites described here for the first time from natural sources, can be potentially enhanced in vivo by stimuli activating phospholipase A₂.     

Testosterone metabolism by mouse placenta in vitro

Zusammenfassung 4-C¹⁴-Testosteron wurde durch Mäuseplazenta in vitro zu Steroiden umgesetzt: 3-Hydroxy-5-androstan-3, 17-dion, 3-Hydroxy-5-androstan-3, 17-dion, 4-Androsten-3, 17-dion und 5-Androstan-3, 17-dion. Eine Umsetzung von Testosteron zu Östrogenen wurde nicht nachgewiesen.     

The effects of some tetracycline derivates on Ehrlich ascites carcinoma and HeLa cells in vitro

Zusammenfassung In-vitro-Nachweis der Hemmung der Proteo- und Nukleosynthese in den EAC-Zellen, sowie des Wachstums der HeLa-Zellen mit folgenden Derivaten des Tetrazyklins: Anhydrotetrazyklin, 4, 12-Anhydrodedimethylaminotetrazyklin und 12-Deoxydedimethylaminotetrazyklin.     

Effects of injury on the concentration ofα 1 andα 2 in the plasmas of male and female rats

Summary The effects of injury on the concentration of ₁-macroglobulin and ₂-macroglobulin in the plasmas of male and female rats has been investigated. At 5 days after injury to the male rats the ₁-macroglobulin concentration increased to 131% of its preinjury value. The ₂-macroglobulin concentration increased more rapidly to a maximum of 86 times its initial value. In the female rats ₂-macroglobulin increased only slightly and ₁-macroglobulin not at all.     

Tumor necrosis factor-α inhibits collagen synthesis in human and rat granulation tissue fibroblasts

The purpose of the study was to examine the effects of tumor necrosis factor- (TNF-) on collagen gene expression in rat and human granulation tissue fibroblast cultures. The cells were exposed to 0.1, 1, 10, or 100 ng/ml of TNF-, and the rate of collagen synthesis was measured as synthesis of protein-bound³H-hydroxyproline. Total cellular RNA was isolated from fibroblasts, and measurements of specific cellular RNAs from fibroblasts were performed by Northern blot hybridizations using³²P-labeled cDNA probes. In cultures of rat granulation tissue fibroblasts TNF- decreased³H-hydroxyproline production to about 75% of that in controls and it also decreased pro1(I) and pro1(III) collagen mRNA levels, maximally to 33% and 23% of the control levels, respectively. In cultures of human granulation tissue fibroblasts a similar inhibiting effect in the production of collagen was seen. TNF- decreased the production of³H-hydroxyproline to 56% of the control value with a dose of 100 ng/ml also having an inhibiting effect on pro1(I) collagen mRNA levels of up to 43% of the control level. However, no effect was seen on pro1(III) collagen mRNA levels.     

Exchange of tritium from randomly tritiated taurocholate by microbial bile salt oxidoreductases

Summary Tritium distribution on randomly labelled taurocholate (TC) was estimated at 28%, 4%, 1% and <0.5% on the hydrogens opposite the 3-, 7- and 12-OH groups and taurine moiety respectively. Anomalously,C. perfringens 3-hydroxysteroid dehydrogenase (3-HSDH) catalyzed tritium loss of 36% on formation of 7-, 12-dihydroxy-3-keto-5-cholanoate, implying additional losses of tritium at other sites by this enzyme.This work is supported by the National Cancer Institute.     

Age- and sex-related differences in the content of prothymosinα in rat tissues

Differences in the tissue content of prothymosin during the early postnatal development of male and female rats are reported. Thymus and spleen have been found to contain significantly higher amounts of prothymosin in the newborn and prepubertal animals, as compared to adults, whereas liver has been found to contain low levels of prothymosin throughout development. These findings indicate a functional association of prothymosin with the proliferating lymphoid tissues of the young rat.     

Carbohydrase and esterase activity in the gut of larvalCallosobruchus maculatus

Summary Carbohydrase activity has been demonstrated in homogenates of the alimentary tracts of late instar larvae ofC. maculatus:-D galactosidase, -D glucosidase and N-acetyl-D glucosaminidase activities were comparable and significantly greater than -D galactosidase,-D glucosidase and -D mannosidase. The effects of pH and substrate concentration are reported. The presence and changes in pattern of non-specific esterase activity in larval and adult gut homogenates is also described.     

ω10-Lipoxygenase products of α-linolenic acid are esterified to phospholipids inHydra vulgaris

We have recently reported the occurrence of 9(R)-hydroxy-, 9(R)-hydroperoxy- and 9-keto-octadeca-10E,12Z,15Z-trienoic acids (9-HOTrE, 9-HPOTrE and 9-KOTrE) inHydra vulgaris, and their biosynthesis from -linolenic acid (-LA) through the action of an enantioselective 10(R)-lipoxygenase (10-LO). Here we describe the finding of these -LA metabolites as esters to the 2-position of phosphatidylcholine, phosphatidylethanolamine and, in trace amounts, phosphatidylinositol. Small amounts of a compound co-eluting with an authentic standard of 9(R)-hydroxy-octadeca-10E,12Z-dienoic acid, a metabolite potentially derived from the action of 10-LO on linoleic acid, were also found esterified with phospholipids. Since direct peroxidation of membrane lipids has been described, experiments were aimed at establishing whether -LA metabolite-containing phospholipids could originate, inH. vulgaris, from either spontaneous or 10-LO-catalyzed oxidation of phospholipid-bound -LA. Incubation of either unlabelled or radiolabelled PUFA-containing phosphoglycerides withH. vulgaris 10-LO did not result in their peroxidation. This suggests that -LA and LA metabolites are incorporated into glycerophospholipids after their formation by 10-LO, and that, as in mamals, membrane phospholipids may serve as a reservoir for these bioactive compounds. This is the first example in an invertebrate species of lipoxygenase products esterified to phosphoglycerides.     

Antigastric secretory activity of 4-chloro-α,α-dimethylphenethylaminopropan-2-one and related compounds

Zusammenfassung AY-14,948 [4-Chlor-,-Dimethylphenethylaminopropan-2-on] setzt die basale Ausscheidung von Magensäure in der Ratte herab. Die Prüfung der strukturverwandten Verbindungen ergab, dass AY-18,672 [,-Dimethylphenethylaminopropan-2-on] in dieser Hinischt wirksamer ist als AY-14,948, indem es auch die reserpinbedingte Erregung der Magensäureausscheidung blockiert.     

A new antiandrogen. 6α-Bromo-17β-hydroxy-17α-methyl-4-oxa-5α-androstan-3-one

Zusammenfassung Es wird gezeigt, dass 6-Brom-17-hydroxy-17-methyl-4-oxa-5-androstan-3-one beträchtliche antiandrogene Wirkung besitzt. Isomere dieser Verbindung mit verschiedener Konfiguration an C-5 und C-6 wurden als inaktiv befunden.     

A postsynaptic α, 2-receptor: The alpha-adrenergic receptor of hamster white fat cells

Summary The effects of selected -agonists and -antagonists on theophylline-induced lipolysis were investigate in isolated hamster white fat cells ₂-Agonists (tramazoline, clonidine) inhibited theophylline-induced lipolysis while an ₂-agonist (methoxamine) was without any effect. The inhibitory effect of ₂-agonists was suppressed by yohimbine (₂-antagonist), whereas ₂-antagonists were inefficient. This result implies that the -adrenergic receptor of hamster fat cells is of the ₂-type, although located postsynaptically.Acknowledgments. This work was supported by grants from CNRS (ERA 412) and DGRST (grant No. 787 1078). We thank M. Dauzats for excellent technical assistance. We thank Prof. H. Schmitt for tramazoline and AR-C 239 and for helpful discussion.     

Lack of tolerance development to tumor necrosis factor α inside the central nervous system

Tumor necrosis factor (TNF) was repeatedly microinfused into the lateral ventricle of guinea pig brains at a dose of 200 ng, 4 times within 150 min, at intervals of 3 days. In comparison to guinea pigs infused with solvent according to the same time schedule, the animals responded to TNF with pronounced fevers. The quantity of the fever response was the same after each of the 4 microinfusions of TNF. Three days after the last infusion of TNF or solvent all animals received an intramuscular injection of bacterial lipopolysaccharide (LPS). The fever in response to LPS was the same in both groups. Thus, the reported development of tolerance to repeated systemic administration of TNF^1–3 does not develop inside the blood-brain barrier. Also, the febrile response to LPS is not influenced by repeated central pre-treatment with TNF, whereas repeated peripheral treatment does have an effect.     

Changes of the level of proteinase inhibitors in rat plasma during turpentine-induced inflammation

Summary The levels of rat plasma -macroglobulins, -cysteine proteinase inhibitor, haptoglobin and antipapain activity were studied during the acute-phase reaction after an injection of -pinen. An increase in concentration of all the compounds examined was observed.     

Die Wirkung von Progesteron und Progesteronmetaboliten auf das Wachstum von embryonalem Knorpel in vitro

Summary Embryonic chick bones were cultured in vitro in the presence of progesterone and of a series of progesterone metabolites. It was found that only 5-pregnane-3,20-dione, 3-hydroxy-5-pregnane-20-one, and ⁴-pregnene-20-ol-3-one influence the growth of bones in vitro in a manner similar to progesterone. All other investigated progesterone metabolites exert either a different or no demonstrable action on bone growth.