Effects of female sex hormones on mitochondria: possible role in acute fatty liver of pregnancy.
Acute fatty liver of pregnancy occurs in some women. As other cases of microvesicular steatosis are due to impaired mitochondrial oxidation of fatty acids, we investigated the effects of female sex hormones on liver mitochondria in female mice. Three hours after administration of both estradiol (36 mumol/kg) and progesterone (150 mumol/kg), the in vitro beta-oxidation of [U-14C]palmitic acid and the activity of the tricarboxylic acid cycle decreased 49 and 54%, whereas the in vivo oxidation of [U-14C]palmitic acid decreased 38%. One week of treatment with both sex hormones produced ultrastructural lesions of mitochondria, decreased the recovery of mitochondrial proteins by 34%, increased state 4 respiration by 54-77%, and decreased the activities per gram of liver of several enzymes involved in the activation, mitochondrial uptake, and oxidation of fatty acids by 34-54%. We conclude that female sex hormones have deleterious effects on liver mitochondria and suggest that these effects, together with other factors, may contribute to the development of acute fatty liver of pregnancy in some women.
Institut National de la Santé et de la Recherche Médicale Unité-24, Clichy, France.
S
S
Grimbert
C
C
Fisch
D
D
Deschamps
A
A
Berson
B
B
Fromenty
G
G
Feldmann
D
D
Pessayre
D000208:Acute Disease; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005234:Fatty Liver / Q000209:etiology*; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology*; D011374:Progesterone / Q000494:pharmacology*; D013997:Time Factors
D011374:Progesterone; D004958:Estradiol