sermorelin and Acute-Disease

Anorexia nervosa is associated with several abnormalities in GH secretion elicited by different stimuli. To investigate the precise mechanism of this alteration, GHRH was administered to 14 women: a group of eight anorexia nervosa patients in the acute phase of their illness and a control group of six age-matched volunteers. As patients with anorexia nervosa have chronic low oestrogen values, the volunteer women of the control group underwent a second GHRH test after pretreatment with the oestrogen receptor blocker tamoxifen. GHRH 1-29 (1 microgram/kg i.v.) induced a GH peak (mean +/- SEM) of 28.2 +/- 5.1 ng/ml (GH ng/ml x 2 = mU/l) at 30 min in the anorectic patients. This value was no different from the GHRH-stimulated GH peak in the control women (28.1 +/- 10.0 ng/ml). Tamoxifen pretreated women had a GH peak after GHRH of 35.6 +/- 9.7 ng/ml, not significant versus control test. Compared with the control group, oestrogen levels were significantly lower in anorectic patients and higher in tamoxifen-treated women. GHRH administration induced a small PRL peak at 15 min that was similar in the three groups tested. After this 15 min peak, PRL in both anorexic and tamoxifen-treated women returned toward basal values steadily. However, in untreated control women a second PRL peak was evident at 60 min. In conclusion, GHRH-induced GH secretion in anorexia nervosa patients was similar to that in control subjects and in controls under oestrogen receptor blockade.

Topics: Acute Disease; Adolescent; Adult; Anorexia Nervosa; Female; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Peptide Fragments; Prolactin; Sermorelin; Tamoxifen

The aim of the current study is to investigate the effects of growth hormone releasing hormone (GHRH) antagonist on acetaminophen (APAP)-induced acute liver injury in mice. Healthy C57/B6L mice were orally treated with 200 mg/kg APAP with or without a 30-min pre-treatment with 300 µg/kg GHRH antagonist MZ-5-156. After 12 hours, serum, plasma, and liver samples from each mouse were collected for analyses. Our results showed that twelve-hour treatment with APAP caused obvious liver injury, elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, increased oxidative stress, reduced expressions of antioxidant enzymes, accumulated expression of pro-inflammatory cytokines, and increased circulating levels of growth hormone (GH) and insulin-like growth factor-I (IGF-I). Pre-treatment with MZ-5-156 aggravated liver injury, further increased serum ALT and AST levels, exacerbated oxidative stress and inflammation induced by APAP. Treatment of MZ-5-156 also blocked the phosphorylation form and total form of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5). Treatment of GHRH super-agonist JI-38 immediately after MZ-5-156 treatment partly reversed the liver injury caused by APAP and MZ-5-156. In conclusion, GHRH plays essential protective role in APAP-induced acute liver injury in vivo. The protective properties of GHRH are partially through GH/IGF-I axis and JAK/STAT pathway.

Topics: Acetaminophen; Acute Disease; Animals; Chemical and Drug Induced Liver Injury; Drug Evaluation, Preclinical; Drug Interactions; Growth Hormone; Growth Hormone-Releasing Hormone; Hormone Antagonists; Insulin-Like Growth Factor I; Male; Mice; Mice, Inbred C57BL; Sermorelin; Signal Transduction