Female sex hormones, perinatal, and peripubertal androgenization on hepatocyte insulin dynamics in rats.
The effects of female sex hormones on insulin binding and receptor-mediated insulin degradation were investigated in hepatocytes from ovariectomized rats. The influences of perinatal and peripubertal androgenization on these events were examined. Estradiol treatment increased insulin binding and receptor-mediated insulin degradation by increasing cell surface insulin receptor number. Progesterone also increased both binding and degradation, but the increase in degradation exceeded the increase in binding. Perinatal exposure to testosterone blunted the estradiol-induced increase in insulin binding and decreased degradation, whereas the progesterone-mediated increases were completely suppressed. Peripubertal testosterone decreased binding, with a much greater reduction in insulin degradation. Perinatal androgenization did not influence the peripubertal testosterone effects. Thus peripubertal female sex hormones exert regulatory influences on both hepatic cell surface insulin receptor number and postreceptor events mediating insulin degradation. These events are modulated by perinatal and peripubertal exposure to androgens. Abnormalities in sex hormone levels and/or hepatic androgenization could therefore contribute to altered insulin metabolism and hyperinsulinemia in some hyperandrogenized women with abdominal obesity and increased androgenic activity.
Krakower
G R
GR
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226.
Meier
D A
DA
Kissebah
A H
AH
D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007328:Insulin / Q000378:metabolism* / Q000502:physiology; D008099:Liver / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D013739:Testosterone / Q000378:metabolism / Q000502:physiology; D014770:Virilism / Q000209:etiology / Q000503:physiopathology*
D000728:Androgens; D007328:Insulin; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D011972:Receptor, Insulin