Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2012) 28 OC1.1

SFEBES2012 Oral Communications Young Endocrinologists prize session (8 abstracts)

Functional characterisation and translational clinical applications of kisspeptin-10

Jyothis George 1 , Richard Quinton 4 , Jacques Young 5 , Johannes Veldhuis 3 , Robert Millar 2 & Richard Anderson 1


1MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom; 2Centre for Integrative Physiology, University of Edinburgh, Edinburgh, United Kingdom; 3Endocrine Research Unit, Mayo Clinic, Rochester, MN; 4Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom; 5Service d’Endocrinologie et des Maladies de la Reproduction, Hôpital de Bicêtre, Paris, France.


Hypothesis: Exogenous kisspeptin-10 (Kp10) enhances pulsatile LH. Research strategy: A first-in-man dosing study of kp10 was first performed. Healthy volunteers and hypogonadal patients were subsequently infused with kp10. Dose titration study Rapid increases in LH with clear dose-dependency (P<0.0001) were observed in healthy men (n=6), with the 0.3 and 1 µg/kg doses being maximally stimulatory (P<0.01). Effect of sex-steroid milieu: LH responses to iv Kp10 (0.3 µg/kg,) in the follicular phase (n=10) was compared with that in postmenopausal women (n=6) and in women taking combined contraceptives (n=8). LH increased significantly and comparably following Kp10 in the follicular phase (6.3±1.2 to 9.4±1.3 IU/L P=0.006), postmenopausal (35.3±2.8 to 44.7±3.4 IU/L P=0.005) and COCP groups (2.2±0.9 to 3.7±1.4 IU/L P<0.001). Pulse-frequency study: LH pulses increased in healthy men from 0.7±0.1 to 1.0±0.2 pulses/hr (P = 0.01) during a 12 hr 4 µg/kg per hr infusion, with LH increasing from 5.2±0.8 to 14.1±1.7 IU/L (P<0.01). High dose infusion study: Four healthy men were admitted for 34 hrs and an infusion of Kp10 (4 µg/kg per hr) maintained for 22.5 hrs. LH increased from 5.5±0.8 to 20.9±4.9 IU/L (P <0.05) and testosterone from 16.6±2.4 to 24.0±2.5 nmol/L (P <0.001). Studies in hypogonadal patients: An infusion of kp10 (4 mcg/kg per hr) increased LH (3.9±0.1 to 20.7±1.1 IU/L (P=0.03) and testosterone (8.5±1.0 to 11.4±0.9 nmol/L, P=0.002) in T2DM. LH pulse-frequency at baseline was lower in T2DM (0.6±0.1 vs. 0.8±0.1 pulses/hr, P=0.03) and increased to 0.9±0 pulses/hr (P=0.05. Mean LH and LH pulse-frequency increased with kisspeptin-10 (P<0.05) in patients with TAC3 or TACR3 mutations. However, individuals with Kallmann syndrome did not respond.

Summary of LH Responses to kisspeptin-10 and GnRH Kisspeptin-10 (0.3 mcg/kg) was administered as bolus with 15-min blood sampling for 3 hours before and after.

Conclusions: Kisspeptin-10 increases LH pulse frequency. Proof-of-concept studies demonstrate potential clinical applications for this novel peptide.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.

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