Insulin signaling in the liver and uterus of ovariectomized rats treated with estradiol.
We used rat hepatic and uterine tissues to examine the impact of estradiol (E2) on insulin (INS) signaling. Ovariectomized (OVX) female Wistar rats were treated with E2 (20 microg/kg b.wt., i.p.) and used for the experiment 6h after E2 administration. To highlight E2 effects on tyrosine phosphorylation of INS receptor (IR) and INS receptor substrates (IRSs) and IRSs association with p85 subunit of phosphatidylinositol 3-kinase (PI3-K) in the context of INS signaling, E2-treated OVX rats were also injected with INS (20 IU, i.p.), 30 min before the experiment. Treatment with E2 did not change the levels of plasma INS and glucose (Glu). However, it significantly decreased the free fatty acid (FFA) level and increased uterine weight. Furthermore, the results show that E2 had no effect on the content of hepatic IR protein, but significantly increased IR protein content in the uterus and decreased IR tyrosine phosphorylation in both the liver and uterus. Compared to the control, hepatic IRS-1 and IRS-2 were significantly decreased and increased, respectively, after E2 treatment. Protein content of both molecules, IRS-1 and IRS-2, was increased in uterine tissue after E2 administration. Protein content of the p85 subunit of PI3-K and that of protein kinase B (Akt) were increased in the uterus, with no changes in the liver. The results suggest that E2 treatment induces tissue-specific changes in INS signaling. The consequences of E2 treatment on INS signaling molecules are more apparent in the uterus, but their physiological relevance for INS action is probably greater in the liver.
Koricanac
G
G
Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, Belgrade, Serbia. gogi@rt270.vin.bg.ac.yu
Milosavljevic
T
T
Stojiljkovic
M
M
Zakula
Z
Z
Ribarac-Stepic
N
N
Isenovic
E R
ER
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004958:Estradiol / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D007328:Insulin / Q000097:blood / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D004958:Estradiol; D011972:Receptor, Insulin