4.4 Article

A single injection of kisspeptin-54 temporarily increases luteinizing hormone pulsatility in healthy women

Journal

CLINICAL ENDOCRINOLOGY
Volume 79, Issue 4, Pages 558-563

Publisher

WILEY
DOI: 10.1111/cen.12179

Keywords

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Funding

  1. NIHR Clinical Lectureship
  2. AMS/Wellcome Starter Grant for Clinical Lecturers
  3. Society for Endocrinology Early Career Grant
  4. Imperial College Healthcare Charity Fellowship
  5. Wellcome/GSK Translational Research Fellowship
  6. NIHR Career Development Fellowship
  7. MRC
  8. Integrative Mammalian Biology (IMB) Capacity Building Award
  9. NIHR Biomedical Research Centre Funding Scheme
  10. MRC [G0701679, G1000455] Funding Source: UKRI
  11. Academy of Medical Sciences (AMS) [AMS-SGCL5-Jayasena] Funding Source: researchfish
  12. Medical Research Council [G1000455, G0701679] Funding Source: researchfish
  13. National Institute for Health Research [CDF-2009-02-05, ACF-2008-21-018, ACF-2013-21-007, CL-2009-21-004, ACF-2010-21-015] Funding Source: researchfish

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Background Kisspeptin is a novel hypothalamic peptide which stimulates endogenous gonadotrophin releasing hormone (GnRH) secretion. A single subcutaneous bolus injection of kisspeptin-54 increases circulating luteinizing hormone (LH) levels in women, but its acute effects on LH pulsatility are not known. Aims To investigate the effects of a single subcutaneous (sc) injection of kisspeptin-54 administration on LH pulsatility in healthy female volunteers. Methods Six healthy female adult volunteers underwent 10-minute blood sampling for serum LH measurement for 8 h during the follicular phase of menstrual cycle. Sc bolus injection of saline or kisspeptin-54 (0.15, 0.30 or 0.60 nmol/kg) was administered 4h after commencing the study. A previously described, blinded deconvolution method was used to detect LH pulses. Results Mean number of LH pulses was increased significantly following 0.30 and 0.60 nmol/kg kisspeptin-54 when compared with saline (mean increase in number of LH pulses per 4h, following injection: -0.17 +/- 0.54, saline; +2.33 +/- 0.56, 0.30 nmol/kg kisspeptin-54, P < 0.05 vs saline; +2.33 +/- 0.80, 0.60 nmol/kg kisspeptin-54, P < 0.05 vs saline). LH pulse secretory mass increased following injection of 0.60nmol/kg in five of six subjects, but the mean change in all subjects was non-significant when compared with saline (mean increase in pulse secretory mass in IU/l following injection: +0.35 +/- 0.40, saline; +2.61 +/- 1.17, 060nmol/kg kisspeptin-54, P = 0.10 vs saline). Conclusions A single injection of kisspeptin-54 temporarily stimulates the number of LH pulses in healthy women. Further studies are required to investigate the therapeutic potential of kisspeptin-54 injection to restore LH pulsatility in patients with reproductive disorders caused by impaired GnRH secretion.

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