LUTEINIZING-HORMONE PULSATILITY IN SUBJECTS WITH 5-ALPHA-REDUCTASE DEFICIENCY AND DECREASED DIHYDROTESTOSTERONE PRODUCTION

The pattern of LH pulsatility in male pseudohermaphrodites with inherited 5 alpha-reductase-2 deficiency (5 alpha RD) and decreased levels of plasma dihydrotestosterone was compared to that in normal males. Analysis of 10-min plasma LH sampling during either a 10- or 24-h period demonstrated that the subjects with 5 alpha RD had 1) a mean plasma LH level, mean LH pulse amplitude, and mean plasma LH nadir that were approximately twice normal; and 2) a mean LH pulse frequency similar to that in normal males, whether described as pulses per h or pulses per study period. An increased plasma LH response to GnRH administration was also noted. The findings suggest that a deficiency of DHT results in decreased negative feedback at the level of the hypothalamus and/or pituitary, resulting in an increase in mean plasma LH, LH pulse amplitude, and LH responsiveness to GnRH. In response to increased LH, mean plasma testosterone (T), free T, and plasma estradiol (E(2)) are increased. The pulse amplitude is increased despite elevated plasma T and E(2) levels; this underscores the importance of DHT in pulse amplitude regulation. LH pulse frequency is not decreased despite elevated plasma T and E(2), raising the possibility that DHT deficiency increased pulse frequency that was normalized by increased T and/or E(2) In conclusion, studies of LH pulsatility in subjects with 5 alpha RD suggest a role for DHT in the modulation of LH.