3. Laboratory of Physiological Genetics.

(1) Staff:

• Ludmila N. Ivanova, Prof., Dr. Sci., Head of the Laboratory
• Nadezhda M. Bazhan, Ph.D.
• Ninel S. Logvinenko, Ph.D.
• Nina N. Melidi, Ph.D.
• Marina N. Zelenina, Ph.D.
• Alexander A. Tinnikov, Ph.D.
• Viktor A. Shulga, Ph.D.
• Igor I. Khegay, Ph.D.
• Evgeny I. Solenov, Dr.Sci.
• Tamara G. Amstislavskaya, Ph.D.
• Tatjana V. Yakovleva

(2) Subject of Research:

• Molecular and genetics mechanisms of hormone regulation of functional systems in ontogenesis of mammals.
• Physiological and genetics mechanisms of maintenance of agouti locus polimorphism in the water vole.
• The functional role of corticosteroid-binding globulin in the corticosteroid regulation of adaptive and developmental processes.

(3) General Results 1993-1995:

• The development of mechanisms of vasopressin action were investigated. We have found that expression of coupling Gs-protein alpha-subunit mRNA in the rat renal papilla revealed the specific developmental pattern with maximal level during the first week after birth and at the end of weaning. Binding and catalytic activity of papillary cytosolic cAMP-dependent protein kinases display similar ontogenetic changes. Resembling age-related changes were demonstrated also for actin gene expression in rat renal papilla. We conclude that the development of the different components of VP signal transduction mechanism follows the common pattern, the complicated character of which may reflect the complexity of the process of the formation of integrated system of VP stimulus realization.
• Mapping of the vasopressin gene in Rattus Norvegicus was carried out. We have established the position of the gene in the fourth linkage group of the Rattus Norvegicus. Using the in situ hybridization we have mapped the vasopressin gene to chromosomal region 3q41-q42 in the rat karyotype.
• Hyaluronate hydrolases of the amphibian urinary bladder were demonstrated to involve to the hydroosmotic effect of vasopressin. An exposure of isolated frog urinary bladders to AVP was found to increase the net water flow simulteniously with the enhancment of the hyaluronate hydrolases (HH) activities. The activities of other lysosomal enzymes (beta-galactosidase and acid phosphatase) remained unchanged. Cytochalasin B and glutaraldehyde blocked the hydroosmotic response to AVP. It suggested that VP induces the specific activation of HH and their release out of epithelial cells by cAMP-dependent mechanism.
• We investigated the level of glucocorticoids and corticosteroid-binding globulin (transcortin) in blood during starvation, increase of blood pressure, and reperfusion under heart surgery. It is established that transcortin have adaptive significance independently on adrenocorticoid level.
• The effects of food deprivation on day 15 and again on day 18 of the pregnancy on the reproduction of the water vole females and their female and male progeny were examined. In the group of deprived mothers fecundity was diminished and litter sex ratio was skewed toward males. Maternal food deprivation in late pregnancy had no effect on the reproductive performance of male young, but it increased reproductive potency of female young.
• The effects of maternal food deprivation on day 3 and again on day 5 of the pregnancy on the development of gonads and adrenals in female young were examined in the water voles. It was demonstrated that maternal food deprivation before implantation had adverse effect on the overall development and postnatal maturation of endocrine function of gonads and adrenals in female young.
• Families, the residents of the Altai territory exposed to radionuclides pollution, in which cases of hyperbilirubinemia (HBN) in children have been registered, and healthy families were examined. Variation was detected in the level of thyreoid hormones in parents (decrease) and in children with HBN (upper norm level) compared to healthy families, as well as decrease of cortisol excretion and excretory function of kidney in children with HBN and in their sibs without it. Changes in the hormonal status correlate with the changes in psycho-physiological parameters. HBN is supposed to be one of pleiotropic effects of somatic mutations expressed by disturbances in the system which controls the neuroendocrine mechanisms of ontogenesis.

(4) Publications:

1. Tinnikov A.A., Legan M.V., Pavlova I.P., Litasova E.E., Ivanova L.N. (1993). Serum corticosteroid-binding globulin levels in children undergoing heart surgery. Steroids 58:536 -539.
2. Ivanova L.N. (1993). Osmoregulatory function of the kidney in ontogeny. In: Sov. Sci. Rev. F. Physiol. Gen. Biol., Horwood Academic Publishers, pp.141-206.
3. Tinnikov A.A. (1993). On the role of corticosteroid-binding globulin (CBG) in moduluting activity of glucocorticoids: developmental patterns for CBG, corticosterone and alpha-fetoprotein in the ret serum. Japanese Journal of Physiology 43:247-251.
4. Tinnikov A.A. (1993). Corticosteroid-binding globulin levels in the rat serum under conditions of starvation and restriction of motions. Hormone and Metabolic Research 25:88-89.
5. Tinnikov A.A., Legan M.V. (1994). Serum transcortin level in children during heart surgery. European Journal of Physiology 130(Suppl.2):108.
6. Zelenina M.N., Zelenin S.M., Ivanova L.N. (1994). Vasopressin signal transduction during postnatal development. Eur. J. Endocrinol 130(Suppl.2):196.
7. Ivanova L.N., Solenov E.I., Zelenina M.N. (1994). Development of the kidney response to vasopressin at the molecular level. In: Proceedings of 1st European Kidney Research Forum. Kloster Banz, Germany, April 23-27, 1994, p.104.
8. Krymskaya L.G., Gromykhina N.Yu., Tinnikov A.A., Kozlov V.A. (1994). The interaction between Interleukin-1 and glucocorticoids in the in vivo antibody response of mice to three concentrations of antigen. Brain, Behaviour, and Immunity 8:327-340.
9. Tinnikov A.A., Oskina I.N. (1994). Seasonal variations in corticosteroid-binding globulin levels in white laboratory and Norway rats. Hormone and Metabolic Research 26:559-560.
10. Bazhan N.M., Yakovleva T.V. (1994). Maternal stress in early pregnancy and postnatal maturation of adrenals and ovaries. European Journal of Endocrinology 130(Suppl.2):217.
11. Bazhan N.M., Makarova E.N. (1994). Effect of maternal stress in late pregnancy on offspring reproduction in the water vole. In: First World Congress on Stress, Bethesda, Maryland, USA, p.39.
12. Bazhan N.M., Yakovleva T.V. (1994). Adrenal and ovary postnatal ontogenesis in female progeny in the water vole after maternal starvation in early pregnancy. In: Abstracts of 17-th Conference of Euriopean Comparative Endocrinologists, Cordoba, Spain, p.26.
13. Tinnikov A.A., Oskina I.N. (1995). Seasonal pattern for transcortin activity in the rat. Journal of Endocrinolody 144(Suppl):153.
14. Yakovleva T.V., Bazhan N.H., Makarova E.V. (1995). Maternal stress in early pregnancy and offspring reproduction in the water vole (Arvicola terrestris). J. Repr. Fert., AS, 15:73.
15. Gulevitch R.G., Klotchkov D.V., Ivanova L.N., Osadchuk L.V. (1995). Gonadal function in minkunder artificial photoperiods. J. Repr. Fert., 103:147-152.
16. Ivanova L.N., Melidi N.N. (1995). Involvement of hyaluronate hydrolases of the amphibian urinary bladder to the hydroosmotic effect of vasopressin. In: The First Joint World Congress of Neurohypophysis and Vasopressin. Japan, p.112.
17. Khegay I.I. (1995). Mapping of the vasopressin gene in rattus norvegicus. In: The First Joint World Congres of Neurohypophysis and Vasopressin. Japan, p.95.
18. Zelenina M.N., Zelenin S.M. (1995). Mechanism of vasopressin action in developing Kidney. In: The First Joint World Congres of Neurohypophysis and Vasopressin. Japan, p.136.
19. Solenov E.I., Khegay I.I. (1995). Vasopressin receptors in the Kidney of Wistar and Brattleboro rats. In: The First Joint World Congres of Neurohypophysis and Vasopressin. Japan, p.110.
20. Gritsko N., Shulga V., Ivanova L. (1995). Investigations of autonomic nervous system by electrolytes of saliva in man with different constitutional types under vibration exposure. In: Proc. Internat. Conf. 1995 III sec. Human response to vibration 9. England, Silsoe, pp.1-10.
21. Ivanova L.N., Logvinenko N.S., Solenov E.I., Zelenina M.N. (1995). Development of the kidney response to vasopressin and aldosterone at the molecular level. Kidney Internat. 47:660-661.

(5) Participation in State and International Programs:

• State programms:
• Physical-chemical bases of vital activity
• Polygon-Altai
• New Trends in Genetics
• The University of Russia
• RFBR
• International programs:
• International Science Foundation

(6) Subjects of Scientific Collaboration:

• Investigation of the development of molecular mechanisms of kidney responsiveness to vasopressin.
• Investigation of functions and development of aquaporin system in kidney.
• The role of free fatty acids released in response to stress in modulating binding activities of corticosteroid-binding globulin (CBG). Molecular mechanisms underlying adaptive and developmental changes in binding activity of CBG. Functional implications of adaptive and developmental changes in the activity of CBG.
• Maintenance of agouti locus polymorphism.

Abstract.