Testosterone to 17β-estradiol Ratio in Rat Males with Dominant and Submissive Types of Behaviour

Popova L. D., Vasylyeva I. M., Bogdanova T. V.

BIOLOGY

Scentific article

Aggression and suicide are significant problems of modern society. The investigation of features of neurohumoral status in animals predisposed to dominant or submissive types of behaviour and the identification of peripheral markers of these features are very important to prevent the development of aggression and depression in humans. Testosterone is involved in regulation of aggression both in animals and in humans. The conversion of testosterone into estradiol is a key mechanism of many physiological and behavioural processes regulation by testosterone. The objective of the study was to investigate plasma testosterone and 17β-estradiol levels and their ratio in rat males with dominant and submissive types of behaviour. Experiments were carried out on 76 Wistar rat males (three-, six- and twelve-month-old). According to classification of age groups of laboratory animals, tree-month-old rats belong to II period (juvenile); six- and twelve- month-old rats belong to III – reproductive (to young reproductive and mature reproductive, respectively). The animals were separated according to the sensory contact model with some modifications into 3 groups: dominant, balanced and submissive ones. Plasma testosterone and 17β-estradiol levels were determined by method of immune-enzymatic analysis using “Alkor-Bio” and ELISA kits. Statistical analysis of the results was carried out by methods of nonparametric statistics using the package “Statistica 6. 0”. Nonparametric analogues of dispersion analysis – Kruskal-Wallis and median tests – were used to reveal the dependence of parameters on group. Mann- Whitney test and correlation analysis according to Spearman were used to compare groups in pairs. Blood plasma testosterone level was found to vary depending on the period of adulthood. Analysis of blood plasma testosterone level in rats of different age groups but the same behaviour type revealed the following predictability: in rat males independently on a type of behaviour the testosterone level was significantly increased in six-month-old rats versus three-month-old ones and decreased in twelve-month-old rats versus six-month-old ones. No differences were found between testosterone levels in three- and twelve-month-old rats with the same type of behaviour. In all investigated age groups the testosterone level was revealed to depend on behaviour type. It was increased in dominant rat males versus both balanced and submissive ones. Testosterone level in balanced rats was higher than in submissive males but lower than in dominant ones. The most considerable differences were observed in six-month-old rats. The blood plasma 17β-estradiol was revealed to decrease in dominant rat males versus both submissive and balanced ones. The level of 17β-estradiol in balanced rats was higher than in dominant males but lower than in submissive ones. Statistically significant negative correlation between testosterone and 17β-estradiol levels was revealed in all investigated age groups regardless of the behaviour type. Statistically significant differences of testosterone/17β-estradiol ratio were found between males with alternative types of behaviour. The highest ratio of testosterone to 17β-estradiol was found in dominant rat males. Considerable difference between testosterone/17β-estradiol ratio in males with dominant and submissive types of behaviour may be used to determine the predisposition of organism to aggression or depression. The research of testosterone and 17β-estradiol and their ratio in men with different predisposition to aggression will be carried out.

testosterone, 17β-estradiol, dominant and submissive rat males

• Bartolomeos K. Third Milestones of a Global Campaign for Violence Prevention Report WHO Library Cataloguing-In-Publication Data / K. Bartolomeos, D. Brown, A. Butchart [et al.]. – Geneva : World Health Organization, 2007. – 32 p.
• Chichinadze K. N. Is the blood plasma testosterone level linked with aggressive behaviour of prisoner men? / K. N. Chichinadze, T. R. Dominiadze, T. Matitaischvili [et al.]. // Bul. Exp. Biol. Med. – 2010. – Vol. 149, № 1. – P. 11-13.
• Doris A. Depressive illness / A. Doris, K. Ebmeier, Р. Shajahan // Lancet. – 1999. – № 354. – Р. 1369-1375.
• Fava M. Major depressive disorder / M. Fava, K. S. Kendler // Neuron. – 2000. – № 28. – Р. 335-341.
• Gelinas S. α- and β-estradiol protect neuronal but not native PC12 cells from paraquat-induced oxidative stress / S. Gelinas, G. Bureau, B. Valsatro [et al.] // Neurotox. Res. – 2004. – № 6. – P. 141-148.
• Goncalves D. Brain aromatase mRNA expression in two populations of peacock blenny Salaria pave with divergent mating sys- tems / D. Goncalves, J. Saraiva, M. Teles [et al.] // Horm. Behav. – 2010. – Vol. 57, № 2. – P. 155-161.
• Grgurevic N. Aggressive Behaviors in Adult SF-1 Knockout Mice That Are Not Exposed to Gonadal Steroids During Development / N. Grgurevic, T. Bьdefeld, A. S. Tobet [et al.]. // Behav. Neurosci. – 2008. – Vol. 122, № 4. – P. 76-884.
• Hutchison JB. Gender-specific steroid metabolism in neural differentiation / J. B. Hutchison // Cell Mol Neurobiol. – 1997. – Vol. 17, № 6. – P. 603-626.
• Koolhaas J. M. The organization of intraspecific agonistic behaviour in the rat / J. M. Koolhaas, T. Schuurman, P. R. Wiepkema // Prog Neurobiol. – 1980. – № 15. – P. 247-268.
• Kudryavtseva N. N. The sensory contact model for the study of aggressive and submissive behaviours male mice / N. N. Kudry- avtseva // Aggres. Behav. – 1991. – Vol. 17, № 5. – P. 285-291.
• Levin-Allerhand J. A. 17α-estradiol and 17β-estradiol treatments are effective in lowering cerebral amyloid-β levels in AβPPSWE transgenic mice / J. A. Levin-Allerhand, C. E. Lominska, J. Wang, J. D. Smith // J. Alzheimers. Dis. – 2002. – № 4. – P. 449-457.
• Li X. Suicide among the elderly in mainland China / X. Li, Z. Xiao, S. Xiao // Psychogeriatric. – 2009. – № 9. – Р. 62-66.
• Mac Lusky N. J. The 17α and 17β isomers of estradiol both induce rapid spine synapse formation in the CA1 hippocampal sub- field of ovariectomized female rats / N. J. Mac Lusky, V. N. Luine, T Hajszan, C. Leranth // Endocrinology. – 2004. – № 146. – P. 287-293.
• Neumann I. D. Aggression and anxiety: social context and neurobiological links / I. D. Neumann // Front. Behav. Neurosci. – 2010. – № 4. – P. 1-12.
• Nomura M. Genotype/age interactions on aggressive behavior in gonadally intact estrogen receptor beta knockout (betaERKO) male mice / M. Nomura, L. Durbak, J. Chan [et al.] // Horm. Behav. – 2002. – Vol. 41, № 3. – P. 288-296.
• Popova L. D. Determination of behaviour type of rodents / L. D. Popova, I. M. Vasyl’eva // Patent on useful model № 55046 10.12.2010 Bul. № 23 MPK (2009) А61В5/16 U201002821).
• Roselli C. E. Brain aromatization. Classical roles and new perspectives / C. E. Roselli, M. Lice, P. P. Hurn // Semin. Reprod. Med. – 2009. – Vol. 27, № 3. – P. 207-227.
• Scordalakes E. M. Aggression and arginine vasopressin immunoreactivity regulation by androgen receptor and estrogen receptor alpha / E. M. Scordalakes, E. F. Rissman // Genes. Brain Behav. – 2004. – Vol. 3, № 1. – P. 20-26.
• Susman E. J. Hormones, emotional dispositions, and aggressive attributes in young adolescents / E. J. Susman, G. Inoff-Ger- main, E. D. Nottelmann [et al.] // Child. Dev. – 1987. – № 58. – P. 1114-1134.
• Swaab D. F. The stress system in the human brain in depression and neurodegeneration / D. F. Swaab, A. M. Bao, P. J. Lucassen // Ageing. Res. Rev. – 2005. – Vol. 4, № 2. – P. 141-194.
• Taziaux M. Sexual behavior activity tracks rapid changes in brain estrogen concentration / M. Taziaux, M. Keller, J. Bakker, J. Balthazart // J. Neurosci. – 2007. – Vol. 27, № 24. – P. 6563-6572.
• Tepperman J. Metabolic and endocrine physiology an introductory text / J. Tepperman, H. M. Tepperman. – Chicago-London : Year book Medical Publishers, 1987. – P. 177-220.
• Toran-Allerand C. D. 17α-Estradiol: A Brain-Active Estrogen? / C. D. Toran-Allerand, A. A. Tinnikov, R. J. Singh, I. S. Nethrapalli // Endocrinology. – 2005. – Vol. 146, № 9. – P. 3843-3850.
• van Bokhoven I. Salivary testosterone and aggression, delinquency, and social dominance in a population-based longitudinal study of adolescent males / I. van Bokhoven, S. H. van Goozen, H. van Engeland [et al.] // Horm Behav. – 2006. – № 50. – P. 118-125.
• Wingfield J. C. Avoiding the ‘costs’ of testosterone: ecological bases of hormone-behavior interactions / J. C. Wingfield, S. Lynn, K. K. Soma // Brain Behav. – 2001. – № 57. – P. 239-251.
• Witte T. K. Do major depressive disorder and dysthymic disorder confer differential risk for suicide? / T. K. Witte, K. A. Timmons, E. Fink [et al.] // J. Affect Disord. – 2009. – № 115. – Р. 69-78.
• Zapadnuk I. P. Laboratory animals. / I. P. Zapadnuk, V. I. Zapadnuk, E. A. Zaharya, B. V. Zapadnuk. – Kiev : Vyshca Schola, 1983. – P. 22-26.

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