title: Unaltered ratio of circulating levels of growth hormone/GH isoforms in adults with Prader-Willi syndrome after GHRH plus arginine administration.
abstract: Human growth hormone (GH) is a heterogeneous protein hormone consisting of several isoforms, the most abundant being 22 kDa- and 20 kDa-GH. The availability of analytical methods to measure these GH isoforms might represent a valuable diagnostic tool to investigate GH hyposecretory states, including Prader-Willi syndrome (PWS), one of the most common causes of syndromic obesity. The aim of the present study was to measure circulating levels of 22 kDa- and 20 kDa-GH in PWS adults (n=14; M/F: 5/9; genotype DEL15/UPD15: 12/2; age: 19.0±3.7 years; BMI: 29.9±8.7 kg/m2) after combined GH releasing hormone (GHRH) plus arginine (ARG) administration. The results were analysed subdividing the study population in obese vs. nonobese (6/8) and GH deficient vs. nonGH deficient (GHD) (6/8) subjects, according to appropriate BMI-related diagnostic cut-off limits of GH peak response to the provocative test. Circulating levels of 22 kDa-GH were measured by a chemiluminescent method based on a detection monoclonal antibody targeting an epitope in the loop connecting helix 1 and 2 of GH, which is missing in 20 kDa-GH; the 20 kDa-GH was measured using a time resolved fluorescence assay based on two monoclonal antibodies with no cross-reactivity to 22-kDa GH. GHRH plus ARG significantly stimulated the secretions of 22 kDa- and 20 kDa-GH in nonobese (at 30, 45, 60 and 90 min and at 45, 60, 90 and 120 min vs. 0 min, p<0.05, with GH peaks of 15.8±10.3 ng/ml and 2.7±1.2 ng/ml, respectively) and in nonGHD PWS (at 30, 45 and 60 min and at 45, 60 and 90 min vs 0 min, p<0.05, with GH peaks of 12.5±9.0 ng/ml and 2.0±1.8 ng/ml, respectively). No significant GHRH plus ARG-induced changes in 22 kDa- and 20 kDa-GH were observed in obese or GHD PWS patients, the only exception being the increase of 22 kDa-GH (p<0.05) 60 min after the stimulus administration in GHD group (with GH peaks of 6.9±4.7 ng/ml and 0.8±0.6 ng/ml in obese subjects and 8.5±6.0 ng/ml and 1.2±1.0 ng/ml in GHD subjects for 22 kDa- and 20 kDa-GH, respectively). The GH responses for both isoforms were significantly higher in nonobese than in obese PWS patients (at 45 and 60 min for 22 kDa-GH and at 45, 60, 90 and 120 min for 20 kDa-GH, p<0.05), while no differences were detected between GHD vs. nonGHD groups. As previously reported in healthy subjects, the ratios of circulating levels of 22 kDa- to 20 kDa-GH remained constant after GHRH plus ARG both in obese/non-obese and GHD/non-GHD groups, thus suggesting the preservation of a normal balance in GH isoforms in PWS.
authors.affiliation: University of Milan, Department of Clinical Sciences and Community Health, Milan, Italy. Electronic address: antonello.rigamonti@guest.unimi.it.
authors.forename: A E
authors.initials: AE
authors.lastname: Rigamonti
authors.affiliation: Istituto Auxologico Italiano, IRCCS, Experimental Laboratory for Auxo-endocrinological Research, Milan and Verbania, Italy; Istituto Auxologico Italiano, IRCCS, Division of Auxology, Verbania, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Grugni
authors.affiliation: Istituto Auxologico Italiano, IRCCS, Experimental Laboratory for Auxo-endocrinological Research, Milan and Verbania, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Marazzi
authors.affiliation: University of Milan, Department of Clinical Sciences and Community Health, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Bini
authors.affiliation: Endocrine Research Laboratories, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Bidlingmaier
authors.affiliation: Istituto Auxologico Italiano, IRCCS, Experimental Laboratory for Auxo-endocrinological Research, Milan and Verbania, Italy; Istituto Auxologico Italiano, IRCCS, Division of Auxology, Verbania, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Sartorio
mesh_terms: D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000494:pharmacology*; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency / Q000187:drug effects*; D006801:Humans; D007018:Hypopituitarism / Q000097:blood* / Q000150:complications; D008297:Male; D009765:Obesity / Q000097:blood* / Q000150:complications; D011218:Prader-Willi Syndrome / Q000097:blood* / Q000150:complications; D020033:Protein Isoforms / Q000097:blood; D055815:Young Adult
chemical_list: D020033:Protein Isoforms; D019382:Human Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine
keywords: GH deficiency; GH isoforms; GHRH plus arginine; Obesity; Prader–Willi syndrome