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Effect of gonadotropin‐inhibitory hormone on luteinizing hormone secretion in humans
Author(s) -
George J.T.,
Hendrikse M.,
Veldhuis J.D.,
Clarke I.J.,
Anderson R.A.,
Millar R.P.
Publication year - 2017
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.13308
Subject(s) - kisspeptin , endocrinology , medicine , luteinizing hormone , gonadotropin , testosterone (patch) , gonadotropin releasing hormone , area under the curve , hormone
Summary Background Gonadotropin‐inhibitory hormone (Gn IH , 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 Gn IH 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 Gn IH 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 Gn IH (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 Gn IH vs vehicle. Results During Gn IH 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 Gn IH 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 Gn IH , P = 0·72). Exogenous Gn IH 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 Gn IH .