AJP - Endocrinology and Metabolism, Vol 252, Issue 4 E467-E476, Copyright © 1987 by American Physiological Society
Sexual dimorphism in adrenergic regulation of hepatic glycogenolysis
R. K. Studer
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.
