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Direct comparison of the effects of intravenous kisspeptin-10, kisspeptin-54 and GnRH on gonadotrophin secretion in healthy men.

Jayasena CN, Abbara A, Narayanaswamy S, Comninos AN, Ratnasabapathy R, Bassett P, Mogford JT, Malik Z, Calley J, Ghatei MA, Bloom SR, Dhillo WS - Hum. Reprod. (2015)

Bottom Line: How potently does the novel hypothalamic stimulator of reproduction, kisspeptin, increase gonadotrophin secretion when compared with GnRH in healthy men?At the doses tested, intravenous administration of either of two major kisspeptin isoforms, kisspeptin-10 and -54, was associated with similar levels of gonadotrophin secretion in healthy men; however, GnRH was more potent when compared with either kisspeptin isoform.Rodent studies suggest that kisspeptin-54 is more potent when compared with kisspepitn-10; however, their effects have not previously been directly compared in humans, or compared with direct pituitary stimulation of gonadotrophin secretion using GnRH.

View Article: PubMed Central - PubMed

Affiliation: Department of Investigative Medicine, Imperial College London, Hammersmith Hospital, 6th Floor, Commonwealth Building, London W12 0NN, UK.

No MeSH data available.


Related in: MedlinePlus

Protocol diagram for study visits in healthy male subjects. Blood samples taken every 10 min from t = 0 to t = 240 min for serum LH and FSH. Blood samples were also taken for plasma kisspeptin IR at t = 0, 60, 70, 80, 90, 120, 180 and 240 min. After 1 h of baseline blood sampling, the infusions of vehicle, kisspeptin-10, kisspeptin-54 or GnRH were commenced. Maintenance infusion doses were 0.1, 0.3 and 1.0 nmol/kg/h of each peptide. Each participant received the same dose of each peptide in random order at least 1 week apart (n = 5/group). 
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DEV143F1: Protocol diagram for study visits in healthy male subjects. Blood samples taken every 10 min from t = 0 to t = 240 min for serum LH and FSH. Blood samples were also taken for plasma kisspeptin IR at t = 0, 60, 70, 80, 90, 120, 180 and 240 min. After 1 h of baseline blood sampling, the infusions of vehicle, kisspeptin-10, kisspeptin-54 or GnRH were commenced. Maintenance infusion doses were 0.1, 0.3 and 1.0 nmol/kg/h of each peptide. Each participant received the same dose of each peptide in random order at least 1 week apart (n = 5/group). 

Mentions: Patients were admitted to our clinical investigation unit in the morning and asked to lay supine (see Fig. 1 for protocol summary). Baseline blood sampling was performed at 10 min intervals between 0 and 60 min. A single-blinded 3 h continuous intravenous infusion of gelofusin (vehicle), kisspeptin-10 (0.10, 0.30 or 1.00 nmol/kg/h), kisspeptin-54 (0.10, 0.30 or 1.00 nmol/kg/h) or GnRH (0.10, 0.30 or 1.00 nmol/kg/h) was commenced at time 60 min and continued until 240 min (n = 5 subjects per group; see Table II for dose allocation of subjects). The doses selected during this study were based on previous studies that have demonstrated an LH rise during intravenous infusion of kisspeptin-54 in healthy men (Dhillo et al., 2005). A 2-fold higher infusion rate was administered during the first 30 min of each infusion, in order to achieve steady-state plasma levels (Edwards et al., 1999). Therefore, total doses of 0.35, 1.05 or 3.50 nmol/kg peptide were administered during 3 h infusions with maintenance administration rates of 0.10, 0.30 or 1.00 nmol/kg/h, respectively. Blood samples were taken through a cannula at 10 min intervals from t = 0 to t = 240 min to measure gonadotrophin levels. Blood samples were also taken for plasma kisspeptin immunoreactivity (kisspeptin IR) and at t = 0, 60, 70, 80, 90, 120, 180 and 240 min. Study visits for individual patients were scheduled a minimum of a week apart and performed in a random order.Table II


Direct comparison of the effects of intravenous kisspeptin-10, kisspeptin-54 and GnRH on gonadotrophin secretion in healthy men.

Jayasena CN, Abbara A, Narayanaswamy S, Comninos AN, Ratnasabapathy R, Bassett P, Mogford JT, Malik Z, Calley J, Ghatei MA, Bloom SR, Dhillo WS - Hum. Reprod. (2015)

Protocol diagram for study visits in healthy male subjects. Blood samples taken every 10 min from t = 0 to t = 240 min for serum LH and FSH. Blood samples were also taken for plasma kisspeptin IR at t = 0, 60, 70, 80, 90, 120, 180 and 240 min. After 1 h of baseline blood sampling, the infusions of vehicle, kisspeptin-10, kisspeptin-54 or GnRH were commenced. Maintenance infusion doses were 0.1, 0.3 and 1.0 nmol/kg/h of each peptide. Each participant received the same dose of each peptide in random order at least 1 week apart (n = 5/group). 
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4507333&req=5

DEV143F1: Protocol diagram for study visits in healthy male subjects. Blood samples taken every 10 min from t = 0 to t = 240 min for serum LH and FSH. Blood samples were also taken for plasma kisspeptin IR at t = 0, 60, 70, 80, 90, 120, 180 and 240 min. After 1 h of baseline blood sampling, the infusions of vehicle, kisspeptin-10, kisspeptin-54 or GnRH were commenced. Maintenance infusion doses were 0.1, 0.3 and 1.0 nmol/kg/h of each peptide. Each participant received the same dose of each peptide in random order at least 1 week apart (n = 5/group). 
Mentions: Patients were admitted to our clinical investigation unit in the morning and asked to lay supine (see Fig. 1 for protocol summary). Baseline blood sampling was performed at 10 min intervals between 0 and 60 min. A single-blinded 3 h continuous intravenous infusion of gelofusin (vehicle), kisspeptin-10 (0.10, 0.30 or 1.00 nmol/kg/h), kisspeptin-54 (0.10, 0.30 or 1.00 nmol/kg/h) or GnRH (0.10, 0.30 or 1.00 nmol/kg/h) was commenced at time 60 min and continued until 240 min (n = 5 subjects per group; see Table II for dose allocation of subjects). The doses selected during this study were based on previous studies that have demonstrated an LH rise during intravenous infusion of kisspeptin-54 in healthy men (Dhillo et al., 2005). A 2-fold higher infusion rate was administered during the first 30 min of each infusion, in order to achieve steady-state plasma levels (Edwards et al., 1999). Therefore, total doses of 0.35, 1.05 or 3.50 nmol/kg peptide were administered during 3 h infusions with maintenance administration rates of 0.10, 0.30 or 1.00 nmol/kg/h, respectively. Blood samples were taken through a cannula at 10 min intervals from t = 0 to t = 240 min to measure gonadotrophin levels. Blood samples were also taken for plasma kisspeptin immunoreactivity (kisspeptin IR) and at t = 0, 60, 70, 80, 90, 120, 180 and 240 min. Study visits for individual patients were scheduled a minimum of a week apart and performed in a random order.Table II

Bottom Line: How potently does the novel hypothalamic stimulator of reproduction, kisspeptin, increase gonadotrophin secretion when compared with GnRH in healthy men?At the doses tested, intravenous administration of either of two major kisspeptin isoforms, kisspeptin-10 and -54, was associated with similar levels of gonadotrophin secretion in healthy men; however, GnRH was more potent when compared with either kisspeptin isoform.Rodent studies suggest that kisspeptin-54 is more potent when compared with kisspepitn-10; however, their effects have not previously been directly compared in humans, or compared with direct pituitary stimulation of gonadotrophin secretion using GnRH.

View Article: PubMed Central - PubMed

Affiliation: Department of Investigative Medicine, Imperial College London, Hammersmith Hospital, 6th Floor, Commonwealth Building, London W12 0NN, UK.

No MeSH data available.


Related in: MedlinePlus