title: Sex differences in hepatic regulation of cholesterol homeostasis.
abstract: Physiological sex differences may influence metabolic status and then alter the onset of some diseases. According to recent studies, it is now well established that females are more protected from hypercholesterolemia-related diseases, such as cardiovascular diseases until menopause. Female protection from hypercholesterolemia is mediated by the hypolipidemic properties of estrogens, even if mechanisms underlying this protection remain still debated. Even though the regulatory mechanisms of cholesterol homeostasis maintenance are well known, few data are available on the supposed differences between male and female in these processes. So, the aim of this work was to define, through an in vivo study, the putative sex-dependent regulation of the processes underlying cholesterol homeostasis maintenance. We examined 3-hydroxy 3-methylglutaryl coenzyme A reductase and its regulatory protein network as well as the amount of low-density lipoprotein receptor and cholesterol. The study was conducted in the liver and plasma of male and female rats, on adults and during postnatal development, and on 17-beta-estradiol-treated male rats. Our data support that physiological differences in proteins involved in cholesterol balance are present between the sexes and, in particular, 3-hydroxy 3-methylglutaryl coenzyme A reductase shows lower activity and expression in female and 17-beta-estradiol-treated male rats than in adult untreated male. Our data suggest that sex differences in enzyme expression depend on variation in regulatory proteins and seem to be related to estrogen presence. This work adds new evidence in the complicated picture of sex-dependent cellular physiology and establishes a new role for reductase regulatory proteins as a link between estrogen protective effects and cholesterol homeostasis.
authors.affiliation: Department of Biology, University of Roma Tre, Viale Marconi, 446, 00146 Rome, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: De Marinis
authors.forename: Chiara
authors.initials: C
authors.lastname: Martini
authors.forename: Anna
authors.initials: A
authors.lastname: Trentalance
authors.forename: Valentina
authors.initials: V
authors.lastname: Pallottini
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism
chemical_list: C491574:Insig1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051782:Sterol Regulatory Element Binding Protein 2; D004958:Estradiol; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases