Institute Cytology and Genetics

Phisiological Genetics Laboratory

Head Academican of the RAS, Prof. L.N.Ivanova

Development of the cellular mechanisms of vasopressin action is needed for weaning ratlings

Research carried out at the Laboratory is aimed at understanding the molecular-genetic mechanisms regulating functional systems during development in mammals. Progress has been achieved by using various experimental models. In the developing mammalian kidney, the establishment of the sensitivity of vasopressin and aldosterone, the major hormones regulating water salt balance, are under study. It was demonstrated that the kidneys become responsive to vasopressin when all the elements of the system transducing the hormonal signal in the epithelium are mature (from the V2 receptor coupled with adenylate cyclase to the insertion of the protein forming the water channels, aquaporin-2). The key event is an increase in the activities of the V2 receptor gene and of the gene for aquaporin. The integration of the system as a whole gives rise to the sensitivity of the kidneys to vasopressin and to their reabsorptive capacity. Aldosterone starts to stimulate sodium reabsorption in the developing rat kidney from day 20 of postnatal development. It was established at the Laboratory that the effect is related to the formation of the capacity of the cytosolic hormone receptor complex to induce the expression of the mineral corticoid-dependent Na-K-ATPase (sodium pump). This is associated with membrane reception of aldosterone coupled with the secondary messenger system and Na-K-ATP phosphorylation. Phosphorylation of Na-K-ATPase by protein kinase C causes conformational shift and change in enzyme properties.

Work at the Laboratory is also centered on the physiological mechanisms maintaining the diversity for the coat color genes in Arvicola terrestis, the water vole, populations. The water vole population can retain the mutation provided that its gene carriers are superior to the carriers of the other genes in breeding success and viability under extreme (stress) conditions. Black voles, carrying the recessivic mutation nonagouti (a) in the Agouti (A) gene controlling coat color, occurred among brown voles in natural populations. Many year experiments at the Laboratory demonstrated that the hormonal response of the hypothalamic-pituitary adrenal axis to the stress of food and water deprivation was decreased in females with the nonagouti (a) mutation: these females bred better than those of the other genotypes when food deprived: the number of nonagouti (a) offspring born to mothers food deprived during pregnancy was significantly higher. It was concluded that the Agouti gene has a pleiotropic effect on the function of the most important physiological systems providing adaptation to stress (the hypothalamic-pituitary adrenal axis) and the reproductive system. This is additional to the effect the gene has on coat color. The potential of the reproductive capacity of black voles manifested under stress conditions was designated as "adaptive polymorphism". It is the mechanism promoting the retention of the recessive mutation and the maintenance of population heterogeneity for coat color in natural populations.