Link Between the Sensitivity of Kisspeptin Signalling and Pubertal Onset in Boys.

Study Overview
=================
Brief Summary
-----------------
The specific objective of this study was to investigate the sensitivity of Kisspeptin receptor 1 (KISS1R) by determining the responsiveness of GnRH neuron to kisspeptin administration across the pubertal stages and adult group through measuring plasma LH (luteinizing hormone) and testosterone concentrations.

Detailed Description
-----------------
No studies in humans are available regarding KISS1R signalling that, whether expression of the KISS1 or KISS1R sensitivity increases during the pubertal transition in boys. Kisspeptin regulates HPG (hypothalamic pituitary gonadal) axis by secreting GnRH that acts on the pituitary gonadotrophs to secrete LH and FSH. But in contrast to pubertal period, juvenile period kisspeptin pulsatility is reduced, that leads to low GnRH pulsatility and low level of plasma LH, FSH and testosterone. The objective of this study was to determine the response of exogenous kisspeptin in various juvenile stages up to puberty and also in the adults by measuring the level of plasma LH and testosterone. This study would help us to determine that whether there is any link between the increased sensitivity of kisspeptin signalling and puberty onset?, Or at what Tanner stage pre pubertal boys enter into puberty.

Official Title
-----------------
Changes in the Responsiveness of the Hypothalamic-pituitary-gonadal (HPG) Axis to Kisspeptin-10 Administration During Pubertal Transition in Boys

Conditions
-----------------
Reproductive Physiological Phenomena

Intervention / Treatment
-----------------
* Biological: Kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Boys were classified into 5 different Tanner stages (I-V) according to the criteria of Feingold D. In Atlas of physical diagnosis. Pediatric endocrinology. 2nd ed. Philadelphia. WB Saunders; 1992, pp. 16-19. For comparison, adult men were also recruited. Exclusion Criteria: Individuals with chronic illness or disorder, i.e. hepatic and renal complications, epilepsy, pneumonia, asthma, orchitis, hernia, cryptorchidism, mental retardation, etc. were excluded from this study
Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All the groups were injected with exogenous IV kisspeptin according to the body weight.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tanner Stage I<br>A 1ml blood sample was obtained for 30 minutes pre and 120 minutes post-kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany) injection periods at 30 min intervals (-30, 0, 30, 60, 90, 120). The dose was 9.5 µg/BW. | Biological: Kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany)<br>* A neurohormone<br>|
| Experimental: Tanner Stage II<br>A 1ml blood sample was obtained for 30 minutes pre and 120 minutes post-kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany) injection periods at 30 min intervals (-30, 0, 30, 60, 90, 120). The dose was 11.50 µg/BW. | Biological: Kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany)<br>* A neurohormone<br>|
| Experimental: Tanner Stage III<br>A 1ml blood sample was obtained for 30 minutes pre and 120 minutes post-kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany) injection periods at 30 min intervals (-30, 0, 30, 60, 90, 120). The dose was 12.67 µg/BW. | Biological: Kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany)<br>* A neurohormone<br>|
| Experimental: Tanner Stage IV<br>A 1ml blood sample was obtained for 30 minutes pre and 120 minutes post-kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany) injection periods at 30 min intervals (-30, 0, 30, 60, 90, 120). The dose was 15.11 µg/BW. | Biological: Kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany)<br>* A neurohormone<br>|
| Experimental: Tanner stage V<br>A 1ml blood sample was obtained for 30 minutes pre and 120 minutes post-kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany) injection periods at 30 min intervals (-30, 0, 30, 60, 90, 120). The dose was 20.5 µg/BW. | Biological: Kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany)<br>* A neurohormone<br>|
| Experimental: Adult Group<br>A 1ml blood sample was obtained for 30 minutes pre and 120 minutes post-kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany) injection periods at 30 min intervals (-30, 0, 30, 60, 90, 120). The dose was 1 µg/kg. | Biological: Kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany)<br>* A neurohormone<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate the sensitivity of KISS1R by determining the responsiveness of GnRH neuron to kisspeptin administration across the pubertal stages and adult group through measuring plasma luteinizing hormone and testosterone concentrations |  | A time frame for each individual was 3 hours. Kisspeptin-10 was injected intravenously and the blood samples were collected at 30 minutes intervals for 30 minutes pre and 2 hours post kisspeptin-10 injection through cannula. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Puberty, Sexuality