Gender differences in hypothalamic tyrosine hydroxylase and alpha(2)-adrenoceptor subtype gene expression in cafeteria diet-induced hypertension and consequences of neonatal androgenization.
This study investigated the incidence of cafeteria-diet induced hypertension on hypothalamic tyrosine hydroxylase (TH) and alpha(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 alpha(2)-adrenoceptor subtypes. In fact, this diet increased alpha(2A)-adrenoceptor mRNA levels only in intact normotensive females. In contrast, gene expression of the alpha(2B)-adrenoceptor was up-regulated only in male and testosterone-treated female cafeteria-fed rats. Furthermore, an alpha(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 alpha(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 alpha(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.
Department of Biochemistry and Molecular Biology, Faculté de Médecine de Paris-Ouest, Université René Descartes, Paris, France.
Charles
C
Plut
Catherine
C
Ribiere
Yves
Y
Giudicelli
Jean-Pierre
JP
Dausse
D000273:Adipose Tissue / Q000033:anatomy & histology*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D001835:Body Weight; D004032:Diet; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006973:Hypertension / Q000209:etiology; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012147:Restaurants; D012727:Sex Characteristics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D018343:Receptors, Adrenergic, beta-2; D014446:Tyrosine 3-Monooxygenase