Effects of pulsatile and continuous luteinizing hormone (LH) infusions on testosterone responses to LH in rams actively immunized against gonadotropin-releasing hormone

Yearling rams actively immunized against GnRH were used as a hypogonadotropic model for studies of the significance of the pulsatility of LH secretion in determining the trophic actions of the hormone on testicular steroidogenesis. GnRH-immunized rams, in which testicular regression was complete, were infused iv for 12-20 days with ovine LH (NIDDK oLH 24) in three different regimens, delivering a total daily dose of 60 micrograms/100 kg: 1) 1-min pulses of 5 micrograms/100 kg every 2 h (low amplitude, high frequency), 2) 1-min pulses of 30 micrograms/100 kg every 12 h (high amplitude, low frequency), or 3) continuous infusion of 2.5 micrograms/100 kg.h. Serum testosterone levels and acute responses to LH challenges were monitored at intervals throughout the infusion periods. Acute responses to LH were evaluated in terms of the area under the curve for serum testosterone vs. time after LH and the lag time between the infusion of LH and attainment of maximum serum testosterone levels. At the beginning of the experiments, serum testosterone was at castrate values, and testosterone responses to LH were of low magnitude with a long lag time. LH infusion in the low amplitude, high frequency regimen consistently increased the magnitude and decreased the lag time of acute responses to LH; these effects were significant by the sixth day of treatment and persisted for the duration of the experiments. This regimen also had positive effects on morphological features of testes and Leydig cells. Infusion of the high amplitude, low frequency regimen, however, had neither of the positive effects on responsiveness to LH, but did seem to improve testicular and Leydig cell morphology. Continuous infusion of LH also increased the magnitude and decreased the lag time of responses to low amplitude pulses of LH, at least as well as the high frequency infusion regimen did. These results suggest that the high frequency, low amplitude pattern of LH secretion characteristic of reproductively active animals has trophic actions on the testes, increasing their responsiveness to acute gonadotropic stimulation, but the pulsatility of that pattern of LH secretion is not necessary for its trophic actions. The efficacy of high frequency LH secretion may depend only on the elevation of basal or mean LH concentrations, rather than on the low amplitude peaks or the dynamic changes in LH concentrations to which the testes are exposed.