Sex determination in mammals — Before and after the evolution of SRY

Therian mammals (marsupials and placentals) have an XX female: XY male sex chromosome system, which is homologous to autosomes in other vertebrates. The testis-determining gene, SRY, is conserved on the Y throughout therians, but is absent in other vertebrates, suggesting that the mammal system evolved about 310 million years ago (MYA). However, recent work on the basal monotreme mammals has completely changed our conception of how and when this change occurred. Platypus and echidna lack SRY, and the therian X and Y are represented by autosomes, implying that SRY evolved in therians after their divergence from monotremes only 166 MYA. Clues to the ancestral mechanism usurped by SRY in therians are provided by the monotremes, whose sex chromosomes are homologous to the ZW of birds. This suggests that the therian X and Y, and the SRY gene, evolved from an ancient bird-like sex chromosome system which predates the divergence of mammals and reptiles 310 MYA. Received 4 March 2008; received after revision 22 April 2008; accepted 3 June 2008     

Changes in the concentration of adenohypophyseal prolactin and morphological manifestations in the adenohypophysis of lactating rats after administration of D-6-methyl-8-[β-isopropylaminoethyl] ergoline-I

Summary The four days administration of D-6-methyl-8-[-isopropylaminoethyl]ergoline-I (VÚFB-10726) to nursing rats decreases adenohypophyseal prolactin as determined with disc electrophoresis, and produces changes in the histological appearance of adenohypophyses, which indicate the inhibition of prolaction production and secretion.The authors thank Dr.I. J. Skála, Mrs.J. Boubínová, Mrs.J. Emanuelová and Mrs.V. Maitová for technical assistence.     

Levels ofβ-trace protein and lysozyme in human amniotic fluids

Summary The levels of -trace protein and lysozyme were estimated in amniotic fluids from normal fetuses and from fetuses with neuraltube defects. The values of these proteins in normal amniotic fluids were found to be similar to those detected in fetuses with anencephaly and spina bifida. The levels of lysozyme were shown to be correlated with gestational age.     

Biosynthesis ofα- andβ-ecdysone by the CrayfishOrconectes limosus in vivo and by its Y-Organs in vitro

Summary - and -ecdysone were synthesized from labelled cholesterol by premolt crayfish in vivo and by their Y-organs in vitro.     

Completion of the natural groups of ergot alkaloids: Syntheses and pharmacological profiles ofβ-ergosine andβ-ergoptine

Summary The syntheses and pharmacological potencies of -ergosine and -ergoptine, the missing links in the natural groups of ergot peptide alkaloids are described.86th communication on ergot alkaloids.     

The effect of γ-irradiation on the amount of 5-hydroxytryptamine in the gut and spleen in the early phase after irradiation

Résumé 24 et 48 h après irradiation- (900 r) la quantité de 5-hydroxytryptamine dans l'intestin du rat n'a pas changé de manière significative. La quantité de 5-hydroxytryptamine dans la rate du rat, exprimée par g de tissu frais a augmenté. Le prétraitement avec de la cystéamine abaisse nettement la quantité de 5-hydroxytryptamine dans la rate, après l'irradiation.     

Changes in body temperature and circulating levels of interleukin-6 after intra-arterial injections or infusions of tumor necrosis factor α in guinea pigs

Tumor necrosis factor (TNF) is released systematically during the early phase of endotoxin induced fever. To study the effects of this cytokine in guinea pigs, 2 g TNF were intra-arterially injected as a bolus or slowly infused within 60 min. Both modes of administration induced a biphasic elevation of the animals' abdominal temperature lasting 6 h and stimulated the release of endogenous interleukin-6 (IL-6)-like activity. The second phase of the thermal response and the release of endogenous IL-6-like activity were significantly higher, when TNF was slowly infused into the animals' circulation, in spite of a transiently higher TNF-like activity after the bolus injection of TNF. Both TNF and IL-6 may therefore be regarded as candidates to trigger the febrile response in guinea pigs.     

β-Endorphin in normozoospermic and pathologic human semen

Summary -Endorphin was estimated in normozoospermic, oligozoospermic and azoospermic human semen. The mean amount in normozoospermic specimens was 278.6±43.6 (SE) pg/ml while in the others only 191.1±25 pg/ml. Both values are significantly higher than those present in the blood.     

Influence of cyproterone acetate on the activity ofβ-glucuronidase in the hypothalamus and cerebral cortex of the male mouse

Summary Daily s.c. injections of cyproterone acetate greatly decrease the protein content and-glucuronidase activity in the mouse hypothalamus. These effects are reversible and the recovery capacity of the animal seems to be inversely related to the duration of antiandrogenic treatment.Financial aid was given by CNR (finalized project Biologia della Riproduzione) and Ministry of Education. Thanks are also due to Prof. G. Chieffi for suggestions and to Mr R. Auriemma for maintenance of experimental animals.     

Role of Cys221 and Asn116 in the zinc-binding sites of the Aeromonas hydrophila metallo-β-lactamase

The CphA metallo--lactamase produced by Aeromonas hydrophila exhibits two zinc-binding sites. Maximum activity is obtained upon binding of one zinc ion, whereas binding of the second zinc ion results in a drastic decrease in the hydrolytic activity. In this study, we analyzed the role of Asn116 and Cys221, two residues of the active site. These residues were replaced by site-directed mutagenesis and the different mutants were characterized. The C221S and C221A mutants were seriously impaired in their ability to bind the first, catalytic zinc ion and were nearly completely inactive, indicating a major role for Cys221 in the binding of the catalytic metal ion. By contrast, the binding of the second zinc ion was only slightly affected, at least for the C221S mutant. Mutation of Asn116 did not lead to a drastic decrease in the hydrolytic activity, indicating that this residue does not play a key role in the catalytic mechanism. However, the substitution of Asn116 by a Cys or His residue resulted in an approximately fivefold increase in the affinity for the second, inhibitory zinc ion. Together, these data suggested that the first zinc ion is located in the binding site involving the Cys221 and that the second zinc ion binds in the binding site involving Asn116 and, presumably, His118 and His196.Received 3 March 2003; received after revision 4 August 2003; accepted 25 August 2003     

α-andβ-activity of O-methylated derivatives of norepinephrine and epinephrine

Summary Metanephrine, iso-metanephrine, normetanephrine and isonormetanephrine were tested for - and -activity on various tissues obtained from rats, guinea-pigs and cats. It was found that methylation of the hydroxyl groups of norepinephrine or epinephrine in either the 3-or 4-position markedly reduces or abolishes -and -activity with the exception of the nictitating membrane of the cat. This receptor seems to show a tissue difference.Acknowledgment. W. H. V. would like to thank the Federal Republik of Germany for the U. S. Senior Scientist Award which enabled him to work at the Department of Pharmacology, University of Mainz, and to conduct part of this work. W. H. V. would also like to thank Prof. Dr E. Muscholl, Mainz, for his hospitality, help and advice during this stay.     

Action ofβ-(4-chlorophenyl-GABA) on uptake and metabolism of GABA in different subcellular fractions of rat brain

Summary -(4-chlorophenyl)-GABA, a GABA mimetic compound, acts as an inhibitor of GABA metabolism in both synaptosomal and extrasynaptosomal compartments. It has no significant action on GABA or Glu uptake by synaptosomes.     

Involvement of xanthine oxidase and hypoxia-inducible factor 1 in Toll-like receptor 7/8-mediated activation of caspase 1 and interleukin-1β

Inflammatory reactions to ssRNA viruses are induced by the endosomal Toll-like receptors (TLRs) 7 and 8. TLR7/8-mediated inflammatory reaction results in activation of the Nalp3 inflammasome via an unknown mechanism. Here we report for the first time that TLR7/8 mediate activation of xanthine oxidase (XOD) in an HIF-1α-dependent manner. XOD produces uric acid and reactive oxygen species, which could activate Nalp3 and therefore induce activation of caspase 1, known to convert inactive pro-IL-1β into active IL-1β. Specific inhibition of the XOD activity attenuates TLR7/8-mediated activation of caspase 1 and IL-1β release. These results were obtained using human THP-1 myeloid macrophages. The findings were verified by conducting in vivo experiments on mice.     

Dopamine-β-Hydroxylase activity in serum of developing rats

Summary After birth, the activity of dopamine--hydroxylase in rat serum increased up to 14 days maximal level and decreased gradully to reach a low level at 42 days which was about 14% of the activity of maximal activity at 14 days.     

Enterohepatic cycling of O-(β-hydroxyethyl) rutosides and their biliary metabolites in the rat

Summary O-(-Hydroxyethyl)rutosides are shown to undergo reabsorption from the intestine following their secretion in bile.Acknowledgment. The authors wish to thank Mr P. B. Wood and Mr S. D. Godfrey for skilled technical assistance and Zyma, S. A., Nyon, Switzerland, for financial support.     

Effect of glucose and phloretin-2′-β-D-glucose (phloridzin) on in vitro fertilization of mouse ova

Summary The fertilization ratio of mouse ova in vitro decreased when glucose concentration in the medium was lowered. However, the addition of phloretin-2--D-glucose (phloridzin), known as a glucose uptake inhibitor, restored the fertilization ratio back to the control level. The glucose moiety of the phloridzin seemed to be responsible for this effect.     

Correlation between serum dopamine-β-hydroxylase activity and dopamine-β-hydroxylase and tyrosine hydroxylase activities in central and peripheral adrenergic neurons and adrenal glands

Summary Serum dopamine--hydroxylase activity in spontaneously hypertensive rats and Wistar-Kyoto rats had a positive correlation with dopamine--hydroxylase and tyrosine hydroxylase activities in mesenteric vessels, vas deferens, and adrenal glands at 14–16 weeks of age, a negative correlation with dopamine--hydroxylase activity in locus coeruleus at 3 weeks and 14–16 weeks of age, and a positive correlation with tyrosine hydroxylase activity only at 3 weeks of age, but not at 14–16 weeks of age.     

Opposite effects ofβ-adrenoceptor stimulation and 8-bromo-cyclic AMP on potassium efflux in mammalian heart muscle

Summary -adrenoceptor stimulation by isoprenaline increases the potassium efflux in beating guinea-pig atria. This effect is not mimicked by 8-bromo-cyclic AMP, a cyclic AMP analogue which exerts a positive inotropic effect in this preparation.     

Histochemistry of 3β-hydroxysteroid dehydrogenase in monkey adrenal cortex

Zusammenfassung Es wird über mit Hydrocortisonacetat, ACTH und Aldosteronacetat induzierte morphologische und histochemische Veränderungen in der Nebennierenrinde desM. rhesus berichtet. Die bedeutende Verminderung der Steroid-3-ol-dehydrogenasischen Tätigkeit nach Cortisol und deren Zunahme nach ACTH wird hervorgehoben.