CHRONIC INSULIN-TREATMENT, BUT NOT CHRONIC ACTH ADMINISTRATION INCREASES PLASMA DEHYDROEPIANDROSTERONE-SULFATE LEVELS IN ADOLESCENT MALE-RATS

The chronic effect of daily i. m. administration of ACTH (I 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 +/- 0.86 ng/ml) and markedly reduced (0.54 +/- 0.21 ng/ml) in ACTH-treated rats vs. controls (2.33 +/- 0.69 ng/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 +/- 0.09 ng/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 (12 U/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.