Deficits in Pituitary and Brain Cell Nuclear Retention of (3H)Estradiol in Diabetic Rats Deprived of Insulin: Time Course and Metabolic Correlates

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Abstract
Withdrawal of exogenous insulin for 24 h in ovariectomized, streptozotocin-diabetic rats significantly impairs estradiol uptake in whole homogenate fractions of hypothalamus-preoptic area and pituitary gland. Significant reductions in cell nuclear fractions from the same tissues are seen after 36 h of insulin deprivation. Subsequent reinstatement of insulin treatment does not yield full recovery of estradiol uptake after 24 h of insulin replacement. Fat content of the diet has no effect on brain or pituitary estradiol uptake in diabetic animals deprived of insulin for 36 h. Circulating levels of triglycerides, ketones, glucose, glycerol and free fatty acids were found to predict uptake levels to a significant extent, but no single metabolite is reliably predictive across tissues. These data demonstrate that insulin-dependent changes in brain and pituitary uptake of estradiol in rats are slow to develop, and they support the hypothesis that at least some of the reproductive dysfunctions observed in diabetic rats may be the result of impaired cell nuclear estradiol binding in hypothalamus and pituitary.