title: Effect in vivo of endogenous sexual hormones upon the liver mitochondrial function compared in male and female diabetic rats.
abstract: Chronic diabetes induced by the injection of streptozotocin in male and female albino adult rats provoked significant alteration of liver mitochondrial function 30 or 35 days after administration of the drug. Thus, we obtained mean values of respiratory control (RC) and state 3 (S3) with 3-hydroxybutyrate as substrate 40 or 50% lower than those of non-diabetic animals. With other substrates (malate-glutamate, succinate) the decrease of RC and S3 in the diabetic animals was 20% or 30% of the normal mean values. The osmotic damped oscillations of mitochondria were measured as another parameter of the organella function. It was assayed with valinomycin as K+ ionophore and succinate as substrate. In diabetic rats of both sexes we found a significant increase of the mean damping factor of these oscillatory variations compared with normal values. The above-mentioned results indicate a lesser elasticity and an impaired K+ transport of mitochondria across the inner membrane in diabetic animals. Both reported parameters, respiration and oscillatory variations of liver mitochondria, were measured in normal non-diabetic rats and in the groups of diabetic rats referred to as follows: 1) intact (male and female), 2) gonadectomized (male and female), 3) oophorectomized with restitution of 17 beta-estradiol. Ovariectomized diabetic rats showed a significant increase in the values of the RC and S3 of liver mitochondria compared with intact female diabetic animals. The withdrawal of the ovarian hormone in female diabetic rats significantly decreased the values of the damping factors of the oscillatory mechanism and they were similar to the normal. The restitution of 17 beta-estradiol to oophorectomized diabetic rats resulted in a decrease of liver mitochondrial respiration. The damping factor of liver mitochondria of the oophorectomized diabetic rats treated with the estrogen showed values significantly higher than those of female diabetic animals without the hormone and similar to the values of the intact diabetic female rats. Castration of male rats did not produce any effect upon the liver mitochondrial RC and S3 or upon the mean damping factor of the oscillatory variation either. Then the castration of male diabetic rats did not modify the mitochondrial function. In contrast, the oophorectomy of diabetic animals produced amelioration of mitochondrial respiration and oscillatory behavior. The conclusion is drawn that in female rats the circulating 17 beta-estradiol produced a pernicious effect upon liver mitochondrial function in the experimental diabetic state.
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, UBA, Argentina.
authors.forename: J A
authors.initials: JA
authors.lastname: Brignone
authors.forename: C M
authors.initials: CM
authors.lastname: Campos de Brignone
authors.forename: R R
authors.initials: RR
authors.lastname: Rodríguez
authors.forename: A
authors.initials: A
authors.lastname: Marzi
authors.forename: I
authors.initials: I
authors.lastname: Rebagliati de Mignone
authors.forename: M J
authors.initials: MJ
authors.lastname: Rodoni
authors.forename: M C
authors.initials: MC
authors.lastname: Susemihl
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006884:Hydroxybutyrate Dehydrogenase / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009919:Orchiectomy; D010052:Ovariectomy; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D013311:Streptozocin
chemical_list: D004958:Estradiol; D013311:Streptozocin; D006884:Hydroxybutyrate Dehydrogenase