Inhibition of steroid 5α-reductase in vivo: Effect on suppression of luteinizing hormone and stimulation of accessory sex organs by testosterone in the orchidectomized rat

An inhibitor of 5α-reductase, the 17β-carboxylic acid derivative of testosterone (testosterone-17βCA), has been used to evaluate the importance of the 5α-reduction of testosterone in its action on the suppression of LH secretion in male rats. The potential of testosterone-17βCA to inhibit the formation of 5α-dihydrotestosterone (DHT) was first demonstrated in vitro. When homogenates of hypothalami or anterior pituitary glands were incubated with [³H]testosterone in the presence of a 50-fold excess of testosterone-17βCA, the formation of labelled DHT was inhibited by more than 80%. Adult male rats that had been castrated for 1-2 mth were fitted with chronic intravenous catheters and implanted with silicone elastomer sheets: one group received one sheet, 0.5-2.0 cm² in size containing 1.6% testosterone, a second group received one 50 cm² sheet containing 1.6% testosterone-17βCA and a third group received two sheets, one sheet 50 cm² in size containing 1.6% testosterone-17βCA and the second ranging in size from 0.5 to 2.0 cm² and containing 1.6% testosterone. Blood was withdrawn daily from each rat over a 4-5 day period after implantation of the steroids and the level of LH in the plasma was measured by radioimmunoassay. The seminal vesicles and the ventral prostate gland were removed at autopsy on day 4 or 5; the weights of these organs were shown to have increased progressively as the size of the implant of testosterone increased. In contrast, the level of LH in the plasma was suppressed to a comparable extent by implants of testosterone between 0.6 and 2 cm², whereas a 0.5 cm² implant of testosterone had no effect. Implants of testosterone-17βCA alone did not influence the weight of the accessory organs or the level of LH. When testosterone-17βCA and testosterone were implanted together, the growth-promoting effect of the latter on the accessory sex organs was significantly reduced. The effectiveness of testosterone in suppressing the level of LH in the plasma of these animals was not influenced by the presence of testosterone-17βCA and in certain instances the level was raised.