Normalization of estradiol receptor kinetics and hormonal activity in uterus of streptozotocin-induced diabetic rats treated with insulin.

In response to ip 17 beta-estradiol injection, ovariectomized streptozotocin-induced diabetic rats showed a decreased early and late stimulation of uterine protein synthesis as compared to nondiabetic controls. An early nuclear loss of estradiol-receptor complex and an accelerated estradiol clearance from the circulating blood were also observed in these animals. To establish whether these alterations in hormone kinetics and activity were related to the diabetic state, further investigation was done by treating diabetic animals with insulin, during 18 consecutive days after 3 to 8 months of long standing diabetes (type I treatment) or during 10 weeks starting immediately at the onset of the streptozotocin-induced disease (type II treatment). Both types of treatment either restored (type I) or preserved (type II) a normal body weight, low glycemia, and absence of glycosuria. Both types of treatment also restored a normal hormonal clearance so that higher plasma levels of estradiol at 30 and 90 min were noted after ip injection when compared to untreated diabetics. Nuclear retention of the estradiol-receptor complex was significantly higher in treated diabetics at 210 min as compared to the nondiabetic controls. Finally, stimulation of early protein synthesis at 90 min was normalized after both types of treatment. From the above observations it is concluded that insulin treatment restored a normal estrogen metabolism in diabetics, resulting in a prolonged retention of the estradiol-receptor complex in the uterine nuclei; the latter event in turn elicited a normal hormonal activity on protein synthesis. A direct influence of the diabetic state and of insulin treatment on the receptor kinetics and/or on the tissue response to the hormonal stimulus may however not be excluded.