Preservation of GHRH and GH-releasing peptide-2 efficacy in young men with experimentally induced hypogonadism.
BACKGROUND
Somatostatin (SS), GHRH, GH-releasing peptide (GHRP), and the sex-steroid milieu regulate GH secretion.


OBJECTIVE
To test whether GHRH and GHRP remain effective secretagogs in the face of short-term hypogonadism.


METHODS
Prospective, randomized double-blind.


METHODS
Healthy young men (n=24) received a GnRH agonist twice 3 weeks apart followed by placebo (n=13, Pl) or testosterone (n=11, testosterone) addback.


METHODS
were then given consecutive i.v. infusions of l-arginine (to restrain SS outflow) and a maximally effective dose of GHRH or GHRP-2 (to test corresponding secretagog pathways).


RESULTS
GH secretion stimulated by l-arginine/GHRH and by l-arginine/GHRP-2 was unaffected by combined testosterone/estradiol (E(2)) depletion. The low testosterone/E(2) milieu decreased basal (nonpulsatile) GH secretion (P=0.038), without altering fasting pulsatile GH secretion or IGF1 or IGF-binding protein (IGFBP)-3 concentrations. IGFBP-1 (P<0.0001) and abdominal visceral fat (AVF, P=0.017) correlated negatively with fasting basal GH secretion. By contrast, IGF1 (P=0.0012) and IGFBP-3 (P=0.015) correlated positively with fasting pulsatile GH secretion. AVF (P=0.0024) was a negative determinant, and IGF1 a positive determinant (P=0.018), of GHRH-driven GH pulses. Responses to GHRP-2 were unrelated to any of these factors.


CONCLUSIONS
l-arginine/GHRP-2 appears to be an especially robust stimulus of GH secretion, since efficacy is unmodified by profound short-term hypogonadism, a range of AVF estimates, and a spectrum of IGF1, IGFBP-1, and IGFBP-3 concentrations. Whether robustness also applies to chronic hypogonadism is not known.
Veldhuis
Johannes D
JD
Endocrine Research Unit, Mayo School of Graduate Medical Education, Clinical Translational Science Center, Mayo Clinic, Rochester, Minnesota 55905, USA. veldhuis.johannes@mayo.edu
Keenan
Daniel M
DM
Bailey
Joy N
JN
Miles
John M
JM
Bowers
Cyril Y
CY
D000328:Adult; D001120:Arginine / Q000008:administration & dosage; D015331:Cohort Studies; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood / Q000172:deficiency; D005640:Follicle Stimulating Hormone / Q000097:blood; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage* / Q000819:agonists; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D016729:Leuprolide / Q000008:administration & dosage; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage*; D011446:Prospective Studies; D012709:Serum Albumin / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000172:deficiency / Q000494:pharmacology; D055815:Young Adult
C515497:IGFBP3 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D009842:Oligopeptides; D012709:Serum Albumin; D012738:Sex Hormone-Binding Globulin; D019382:Human Growth Hormone; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; C004648:testosterone enanthate; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine; C091874:growth hormone-releasing peptide-2; D016729:Leuprolide