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

Ghulam Nabi, Hamid Ullah, Suliman Khan, Fazal Wahab, Pengfei Duan, Rahim Ullah, Lunguang Yao, Muhammad Shahab, Ghulam Nabi, Hamid Ullah, Suliman Khan, Fazal Wahab, Pengfei Duan, Rahim Ullah, Lunguang Yao, Muhammad Shahab

Abstract

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.

Figures

Figure 1
Figure 1
Comparison of overall mean ± SEM plasma LH and testosterone concentrations observed before and after kisspeptin administration in Tanner stage I boys. Paired t-test showed that post-kisspeptin plasma LH level was comparable to the pre-kisspeptin level. Testosterone level was below the range of detection in both pre- and post-kisspeptin plasma.
Figure 2
Figure 2
(a) Comparison of overall mean ± SEM peak testosterone concentration observed following kisspeptin-10 administration with mean overall basal values in Tanner stage IV boys. Paired t-test on a log-transformed data showed a significant (∗P < 0.05) increase in mean peak testosterone level as compared to the mean basal testosterone value. (b) Comparison of overall mean ± SEM peak LH concentration observed following kisspeptin-10 administration with mean overall basal values in Tanner stage V boys. Paired t-test on a log-transformed data showed a significant (∗P < 0.05) increase in mean peak LH level as compared to the mean basal LH value.
Figure 3
Figure 3
Comparison of overall mean ± SEM plasma LH and testosterone concentrations observed before and after kisspeptin administration in Tanner stage V boys. Paired t-test showed that the post-kisspeptin plasma LH level was insignificant to the pre-kisspeptin level. However, paired t-test on a log-transformed data showed that the post-kisspeptin plasma testosterone level was significantly (∗P < 0.05) increased as compared to pre-kisspeptin level.
Figure 4
Figure 4
Comparison of overall mean ± SEM plasma LH and testosterone concentrations observed before and after kisspeptin-10 administration in adult men. Paired t-test on a log-transformed data showed significant (∗P < 0.05) increase in both post-kisspeptin LH and testosterone levels versus pre-kisspeptin levels.
Figure 5
Figure 5
Comparison of the basal and post-kisspeptin mean ± SEM plasma testosterone level observed at different Tanner stages and adulthood (n = 5/stage). One-way ANOVA followed by a post hoc analysis indicated significant (∗∗P < 0.05) elevation in the mean post-kisspeptin testosterone level at adulthood as compared to Tanner stages I–IV. No significant (P < 0.05) variations in the basal levels of testosterone were observed across the groups.

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