Changes in the Responsiveness of the Hypothalamic-Pituitary-Gonadal Axis to Kisspeptin-10 Administration during Pubertal Transition in Boys

In human, no studies are available regarding changes in kisspeptin1 receptor (KISS1R) sensitivity during pubertal transition. In this study, healthy boys were classified into 5 Tanner stages of puberty (n = 5/stage). Human kisspeptin-10 was administered to boys at each Tanner stage and to adult men (n = 5) as an IV bolus for comparison. Serial blood samples were collected for 30 min pre- and 120 min post-kisspeptin injection periods at 30 min interval for measuring plasma LH and testosterone levels. There was insignificant effect of kisspeptin on LH and testosterone levels in boys of Tanner stages I–III. At Tanner stage IV, the effect of kisspeptin on plasma LH was insignificant. However, a paired t-test on a log-transformed data showed a significant (P < 0.05) increase in mean peak post-kisspeptin testosterone level. In Tanner stage V, a significant (P < 0.05) increase was observed in mean post-kisspeptin peak LH level as compared to the mean basal LH value. Post-kisspeptin plasma testosterone levels were also significantly (P < 0.05) increased as compared to the pre-kisspeptin level in Tanner stage V. Our data suggest that sensitivity of KISS1R on GnRH neurons with reference to LH stimulation in boys develops during the later part of puberty reaching to adult level at Tanner stage V. This trial is registered with WHO International Clinical Trial Registration ID NCT03286517.