Dihydrotestosterone may inhibit hypothalamo-pituitary-adrenal activity by acting through estrogen receptor in the male mouse

Neuroscience Letters
Trent D LundRobert J Handa

Abstract

The corticosterone (CORT) response to environmental perturbation has been shown to be enhanced by estrogen but inhibited by the androgen dihydrotestosterone (DHT). However, the mechanism of androgen's action has not been identified. This study examined the effects of estradiol benzoate (EB), the non-aromatizable androgen DHT, and the DHT metabolite 5alpha-androstan-3beta, 17beta-diol (3beta-diol) on the corticosterone response to stress. Adult male CBB6/F1 mice were gonadectomized and injected subcutaneously (once a day for 4 days) with the above compounds (controls received oil vehicle injections). Animals (within treatments) were randomly assigned to stress or non-stress conditions. The non-stress animals were taken directly from their home cages and killed. Animals were stressed by a 30 min restraint prior to being killed. Hormone levels were determined in plasma via radioimmunoassay. In agreement with previous studies, the CORT response to immobilization was enhanced by EB and inhibited by DHT. Surprisingly, 3beta-diol inhibited the CORT response similar to the effect of DHT. In a second study, concomitant injections of the androgen receptor antagonist flutamide only partially blocked DHT's, but had no effect on 3beta-diol'...Continue Reading

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Citations

Apr 21, 2005·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·David R RubinowLynnette Nieman
Apr 23, 2009·American Journal of Physiology. Endocrinology and Metabolism·Toni R PakRobert J Handa
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