Effect of gonadotropin‐inhibitory hormone on luteinizing hormone secretion in humans. (26th March 2017)

• Record Type: Journal Article
• Authors: George, J.T.; Hendrikse, M.; Veldhuis, J.D.; Clarke, I.J.; Anderson, R.A.; Millar, R.P.
• Is Part Of: Clinical endocrinology. Volume 86:Number 5(2017)
• Page Start: 731
• Page End: 738
• Publication Date: 2017-03-26
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1111/cen.13308
• Languages: English
• ISSNs: 0300-0664

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: <50 pmol/l) and men (39·8 ± 2·1 years, mean total testosterone 12·1 ± 1·8 nmol/l, LH 2·2 ± 0·2 IU/l). Primary outcome: Change in area under curve (AUC) of LH during GnIH 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.