Effect of gonadotropin‐inhibitory hormone on luteinizing hormone secretion in humans

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Abstract
Summary: Background: Gonadotropin‐inhibitory hormone (GnIH, human homologue of RFRP‐3) suppresses gonadotropin secretion in animal models, but its effects have not been studied in the human.Objective: We tested the hypotheses that exogenous GnIH inhibits LH secretion (i) in postmenopausal women and (ii) in men concurrently administered exogenous kisspeptin.Design: Following in vitro and in vivo preclinical studies to functionally characterize the GnIH peptide, a dose‐finding study (human GnIH: 1·5–150 μg/kg/h, iv for 3 h) was undertaken, and 50 μg/kg/h selected for further evaluation. Five postmenopausal women were administered 50 μg/kg/h iv infusion for 3 h or vehicle on two separate days. Four men were administered kisspeptin‐10 (0·3 μg/kg iv bolus) with simultaneous infusion of GnIH (50 μg/kg/h, iv for 3 h) or vehicle.Participants: Healthy postmenopausal women (mean age 58 ± 2 years, LH: 30·8 ± 2·9 IU/l, FSH: 78·7 ± 6·4 IU/l, oestradiol: vs vehicle.Results: During GnIH administration in postmenopausal women, LH secretion decreased (ΔAUC: −9·9 ± 1·8 IU/3 h) vs vehicle (ΔAUC: −0·5 ± 1·7 IU/3 h; P = 0·02). Kisspeptin‐10‐stimulated LH responses in men were not affected by GnIH co‐administration (60‐min AUC of LH 6·2 ± 0·8 IU/h with kisspeptin‐10 alone, 6·3 ± 1·0 IU/h, kisspeptin‐10 with GnIH, P = 0·72). Exogenous GnIH was well tolerated, with no adverse events reported.Conclusions: Gonadotropin‐inhibitory hormone decreased LH secretion in postmenopausal women in this first‐in‐human study. Kisspeptin‐stimulated LH secretion in men was not inhibited during concomitant administration of GnIH.
Funding Information
  • Medical Research Council (G0701682)
  • Ferring

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