Vol. 302, Issue 2, 525-531, August 2002

Gender Differences in Hypothalamic Tyrosine Hydroxylase and ₂-Adrenoceptor Subtype Gene Expression in Cafeteria Diet-Induced Hypertension and Consequences of Neonatal Androgenization

Charles Plut, Catherine Ribiere, Yves Giudicelli and Jean-Pierre Dausse

Department of Biochemistry and Molecular Biology, Faculté de Médecine de Paris-Ouest, Université René Descartes, Paris, France

This study investigated the incidence of cafeteria-diet induced hypertension on hypothalamic tyrosine hydroxylase (TH) and ₂-adrenoceptor subtype gene expression in male, female, and neonatally testosterone-imprinted female rats. After 10 weeks of cafeteria diet, all these rats were hyperleptinemic. In contrast, males and testosterone-treated females developed hypertension, whereas intact females remained normotensive. In these rats, cafeteria diet up-regulated TH gene expression only in males and testosterone-treated females. On the other hand, cafeteria diet differentially affected hypothalamic gene expression of ₂-adrenoceptor subtypes. In fact, this diet increased _2A-adrenoceptor mRNA levels only in intact normotensive females. In contrast, gene expression of the _2B-adrenoceptor was up-regulated only in male and testosterone-treated female cafeteria-fed rats. Furthermore, an _2C-adrenoceptor gene over-expression was also induced, but only in male cafeteria-fed rats. If one assumes that the up-regulations in TH and _2B-adrenoceptor gene expression are indicative of increased sympathetic nervous activity, then, these altered gene expressions could be responsible for the maintenance of high blood pressure in male and testosterone-treated female cafeteria-fed rats. Conversely, in intact females, the absence of these over-expressions and the up-regulation of the _2A-adrenoceptor gene expression could reflect an adaptive response to the diet and, consequently, could be protective against cafeteria diet-induced hypertension. Moreover, neonatal testosterone imprinting in females could have induced an irreversible android susceptibility to the cafeteria diet, leading to the onset of hypertension.