Sexual dimorphism in adrenergic regulation of hepatic glycogenolysis.
The total phosphorylase a plus b of hepatocytes isolated from females and incubated in the absence or presence of estradiol and progesterone at concentrations found in vivo does not vary during the estrous cycle. However, there is a slight but significant influence of the estrous cycle on basal and epinephrine-stimulated phosphorylase a activity, with a nadir being seen on diestrus. The relative contributions of the alpha- and beta-mediated pathways to phosphorylase a activation do not vary with the estrous cycle but are constant at 75 and 56%, respectively, of the response to 5 X 10(-8) M epinephrine. When the epinephrine-stimulated glucose release from glycogen stores in cells from females and males is compared, the release from the female is greater than that from the male, while the alpha-receptor-mediated stimulation in the female is comparable with that in the male. The beta-mediated pathway causes glucose release which averages 45% of that stimulated by epinephrine alone in cells from females. Basal cytosolic free calcium is similar in cells from males and females (142 vs. 149 nM, respectively). The epinephrine-stimulated increase in cytostolic free calcium (Cai) is greater in the male than the female at 10(-6) M (489 vs. 380 nM) but greater in the female than the male at 5 X 10(-9) M (54 vs. 27 nM). The changes in Cai are equivalent at intermediate epinephrine concentrations. When considered with our prior analysis of 45Ca efflux after adrenergic stimulation, this suggests there may be a sexual dimorphism in hepatocyte calcium transport systems. The glucose release for a given increase in Cai is greater in the female than the male probably due to the concomitant action of the beta-mediated increase in cAMP and the alpha-mediated increase in Cai. This supports the conclusion that the beta-mediated component does make a significant contribution to the catecholamine regulation of glycogenolysis in hepatocytes from adult female rats.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004971:Estrus; D005260:Female; D005947:Glucose / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D006005:Phosphorylases / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012723:Sex
D008112:Liver Glycogen; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011374:Progesterone; D004958:Estradiol; D006005:Phosphorylases; D005947:Glucose; D002118:Calcium; D004837:Epinephrine