Chronic Insulin Treatment, but not Chronic ACTH Administration Increases Plasma Dehydroepiandrosterone Sulfate Levels in Adolescent Male Rats

Summary

The chronic effect of daily i.m. administration of ACTH (1 U/kg bodyweight (BW), group A) and of insulin (15 /kg BW, group B) on circulating dehydroepiandrosterone sulfate (DHEA-S) and testosterone was investigated in postpubertal male Wistar rats. NaCl-injected animals served as controls (group C). After at least 8 days under the respective hormone or NaCl treatment “basally” circulating testosterone levels were slightly suppressed in insulin- (1.56±0.86ng/ml) and markedly reduced (0.54 ± 0.21 ng/ml) in ACTH-treated rats vs. controls (2.33 ±0.69ng/ml). DHEA-S levels, however, nearly doubled under chronic insulin administration (0.4 ±0.18 ng/ml) in comparison to the groups A (0.22 ±0.11 ng/ml) and C (0.23 ±0.09ng/ml). Food intake and weight gain were also elevated (vs. groups A and C) as were the basal plasma corticosterone levels (vs. group C) in insulin treated rats. Following an acute ACTH stimulation test (12U/kg BW i. m.) performed in all three treatment groups, plasma DHEA-S showed a further increase in the animals receiving insulin (0.75 ±0.32 ng/ml), whereas no response was detectable in rats from group A (0.27 ±0.13 ng/ml) or C (0.24 ±0.11 ng/ml). Further measurements of corticosterone or testosterone responses following endocrinological stimulation tests with supraphysiological doses of either ACTH or human chorionic gonadotropin (hCG) indicated that a lowering in the catabolism (metabolic clearance) of corticosteroids or androgens could not be the cause for the elevated DHEA-S levels seen after daily insulin injections. In conclusion, chronic low-dose ACTH administration (which partly suppresses the hypothalamic-pituitary axis) obviously fails to raise the plasma DHEA-S concentrations of rats. On the other hand, evidence is provided for a stimulatory long-term effect of insulin on circulating DHEA-S during an anabolic state characterized by an activation of the entire hypothalamic-pituitary-adrenal axis.

Key words

Dehydroepiandrosterone Sulfate - Corticosterone - Testosterone - ACTH - Insulin - hCG