Blockade of endogenous growth hormone-releasing hormone receptors dissociates nocturnal growth hormone secretion and slow-wave sleep. 2004

Stacy K Jessup, and Beth A Malow, and Kathleen V Symons, and Ariel L Barkan
Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Michigan Medical Center, Ann Arbor, Michigan, USA.

OBJECTIVE A temporal association between non-rapid eye movement (NREM) sleep stages 3 and 4 and nocturnal augmentation of GH release was found long ago, yet the precise mechanism for this association has not been identified. It has been shown, however that pulsatile GHRH administration increases both slow-wave sleep (SWS) and GH. Based on these data, a role for GHRH as an inducer of SWS was proposed. To test this hypothesis, we have performed the corollary experiment whereby the action of endogenous GHRH has been antagonized. METHODS Healthy men (20-33 years old) had an infusion of GHRH antagonist ((N-Ac-Tyr(1), D-Arg(2)) GHRH-29 (NH(2))) or saline for a 12-h period, between 2100 and 0900 h. An i.v. bolus of GHRH was given at 0700 h and GH samples were drawn from 0700 to 0900 h to document the efficacy of GH suppression by the GHRH antagonist. METHODS A limited montage sleep study was recorded from 2300 to 0700 h during each admission. Plasma GH concentrations were analyzed by the use of a sensitive chemiluminometric assay. RESULTS Effectiveness of the GHRH antagonist was validated in all subjects by demonstrating 93+/-1.8% (P=0.012) suppression of GH response to a GHRH bolus. Polysomnography demonstrated that the percentage of SWS was not different when saline and GHRH antagonist nights were compared (P=0.607); other quantifiable sleep parameters were also unchanged. CONCLUSIONS We conclude that endogenous GHRH is indispensable for the nocturnal augmentation of GH secretion, but that it is unlikely to participate in the genesis of SWS.

UI MeSH Term Description Entries
D008297 Male Males
D002940 Circadian Rhythm The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli. Diurnal Rhythm,Nyctohemeral Rhythm,Twenty-Four Hour Rhythm,Nycthemeral Rhythm,Circadian Rhythms,Diurnal Rhythms,Nycthemeral Rhythms,Nyctohemeral Rhythms,Rhythm, Circadian,Rhythm, Diurnal,Rhythm, Nycthemeral,Rhythm, Nyctohemeral,Rhythm, Twenty-Four Hour,Rhythms, Circadian,Rhythms, Diurnal,Rhythms, Nycthemeral,Rhythms, Nyctohemeral,Rhythms, Twenty-Four Hour,Twenty Four Hour Rhythm,Twenty-Four Hour Rhythms
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D012894 Sleep Stages Periods of sleep manifested by changes in EEG activity and certain behavioral correlates; they formerly included Stage 1: sleep onset, drowsy sleep; Stage 2: light sleep; Stages 3 and 4: delta sleep, light sleep, deep sleep, telencephalic sleep. In 2007, sleep stages were redefined by The American Academy of Sleep Medicine (AASM) as: N1-N2 (sleep onset - light sleep), N3 (SLOW-WAVE SLEEP), and REM SLEEP. N1-Sleep,N2-Sleep,NREM Stage 1,NREM Stage 2,N1 Sleep,N2 Sleep,Sleep Stage,Stage, Sleep,Stages, Sleep
D013007 Growth Hormone-Releasing Hormone A peptide of 44 amino acids in most species that stimulates the release and synthesis of GROWTH HORMONE. GHRF (or GRF) is synthesized by neurons in the ARCUATE NUCLEUS of the HYPOTHALAMUS. After being released into the pituitary portal circulation, GHRF stimulates GH release by the SOMATOTROPHS in the PITUITARY GLAND. Growth Hormone-Releasing Factor,Somatocrinin,Somatotropin-Releasing Factor 44,Somatotropin-Releasing Hormone,GHRH 1-44,GRF 1-44,Growth Hormone-Releasing Factor 44,Human Pancreatic Growth Hormone-Releasing Factor,Somatoliberin,hpGRF 44,Growth Hormone Releasing Factor,Growth Hormone Releasing Factor 44,Growth Hormone Releasing Hormone,Somatotropin Releasing Factor 44,Somatotropin Releasing Hormone
D017337 Sermorelin The biologically active fragment of human growth hormone-releasing factor, consisting of GHRH(1-29)-amide. This N-terminal sequence is identical in several mammalian species, such as human, pig, and cattle. It is used to diagnose or treat patients with GROWTH HORMONE deficiency. Growth Hormone-Releasing Factor(1-29)Amide,Somatotropin-Releasing-Hormone(1-29)Amide,GHRH(1-29)NH2,GRF(1-29)NH2,Geref,Sermorelin Acetate,hGHRH(1-29)NH2
D018013 Receptors, Neuropeptide Cell surface receptors that bind specific neuropeptides with high affinity and trigger intracellular changes influencing the behavior of cells. Many neuropeptides are also hormones outside of the nervous system. Neuropeptide Receptors,Neuropeptide Receptor,Receptors, Neuropeptides,Neuropeptides Receptors,Receptor, Neuropeptide
D018017 Receptors, Pituitary Hormone-Regulating Hormone Cell surface receptors that bind the hypothalamic hormones regulating pituitary cell differentiation, proliferation, and hormone synthesis and release, including the pituitary-releasing and release-inhibiting hormones. The pituitary hormone-regulating hormones are also released by cells other than hypothalamic neurons, and their receptors also occur on non-pituitary cells, especially brain neurons, where their role is less well understood. Receptors for dopamine, which is a prolactin release-inhibiting hormone as well as a common neurotransmitter, are not included here. Hypothalamic Release-Inhibiting Hormone Receptors,Hypothalamic Releasing Hormone Receptors,Pituitary Hormone-Regulating Hormone Receptors,Pituitary Hormone-Releasing Hormone Receptors,Receptors, Hypothalamic Release-Inhibiting Hormones,Receptors, Hypothalamic Releasing Hormones,Receptors, Pituitary Hormone Release Inhibiting Hormones,Receptors, Pituitary Hormone-Releasing Hormone,Hypothalamic Release Inhibiting Hormone Receptors,Pituitary Hormone Regulating Hormone Receptors,Pituitary Hormone Releasing Hormone Receptors,Receptors, Hypothalamic Release Inhibiting Hormones,Receptors, Pituitary Hormone Regulating Hormone,Receptors, Pituitary Hormone Releasing Hormone
D019382 Human Growth Hormone A 191-amino acid polypeptide hormone secreted by the human adenohypophysis (PITUITARY GLAND, ANTERIOR), also known as GH or somatotropin. Synthetic growth hormone, termed somatropin, has replaced the natural form in therapeutic usage such as treatment of dwarfism in children with growth hormone deficiency. Somatotropin (Human),Somatropin (Human),Cryo-Tropin,Genotonorm,Genotropin,Humatrope,Maxomat,Norditropin,Norditropin Simplexx,Norditropine,Nutropin,Omnitrope,Recombinant Human Growth Hormone (Mammalian),Saizen,Serostim,Somatropin,Umatrope,Zomacton,hGH (Human Growth Hormone),r-hGH(m),r-hGH-M,Cryo Tropin,CryoTropin,Growth Hormone, Human

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