Effect of inhibiting 5α-reductase activity on the ability of testosterone to inhibit luteinizing hormone release in male sheep

Abstract

The extent to which inhibitory effects of testosterone (T) on LH secretion in the ram are mediated by its metabolite dihydrotestosterone (DHT) is unknown. Our objective was to determine the effect of inhibiting 5α- reductase activity on pulsatile patterns of LH release in castrated, T- treated male sheep. Nine Dorset and six Hampshire castrated male sheep were allocated equally to one of three treatment groups: 1) infusion of T (768 μg/kg/day), 2) infusion of the reductase inhibitor (RI) L-651,723 (0.6 mg/kg/day), and 3) T+RI infusion. Treatments were continuously infused for 3 days. Blood samples were collected via an indwelling jugular catheter at 10- min intervals for 4 h immediately prior to (Day 0) and during the final 4 h of infusion (Day 3). Changes in mean LH, LH pulse amplitude, LH interpulse interval (IPI), T, 17β-estradiol (E), and DHT were derived for each animal by subtracting values for Day 0 from Day 3. Data were subjected to one-way analysis of variance. The increase in T and E after infusion of T was similar (p < 0.10) in T- and T+RI-treated males and greater (p < 0.01) than in RI- treated males. The increase of DHT was greater (p < 0.01) in T-treated than either T+RI- or RI-treated males whereas the change was similar (p < 0.10) for T+RI- and RI-treated males. T decreased mean LH more (p < 0.01) than RI. T+RI suppressed mean LH more (p < 0.01) than RI but not as much (p < 0.01) as T alone. The LH IPI was longer (p < 0.05) in T-treated males than in RI- treated males. The LH IPI for T+RI-treated males was intermediate between those in RI-treated (p = 0.06) and in T-treated (p > 0.10) males. Changes in LH pulse amplitude were similar (p > 0.10) for T- and RI-treated males and for T+RI- and RI-treated males. However, LH pulse amplitude was increased (p < 0.05) by T+RI treatment compared to T treatment alone. We conclude that the conversion of T to DHT by 5α-reductase represents a physiologically important step whereby T inhibits LH secretion in the ram.