Central 5-alpha reduction of testosterone is required for testosterone's inhibition of the hypothalamo-pituitary–adrenal axis response to restraint stress in adult male rats

In adult male rats, removal of the gonads amplified both ACTH and corticosterone responses to restraint stress within 48 hours, and testosterone replacement restored the normal stress response. Treating intact males with finasteride for 48 hours produced the same exaggerated stress-hormone response as gonadectomy, showing that blocking 5α-reduction disinhibits the HPA axis. Testosterone's calming effect on the stress response was abolished when finasteride was delivered directly into the brain's third ventricle, whereas the non-aromatizable androgen DHT still suppressed stress responses regardless. The findings indicate that testosterone must be converted to DHT inside the central nervous system to restrain HPA reactivity.