Association of total, acylated and unacylated ghrelin with apolipoprotein A1 and insulin concentrations in acromegalic patients.

BACKGROUND: Ghrelin is a hormone that occurs in acylated (AG) or unacylated (UG) form. Ghrelin strongly stimulates growth hormone (GH) secretion from anterior pituitary, as well as regulates the energy balance and various metabolic parameters. Increased consideration is given to UG, thought to be inactive. OBJECTIVES: We aimed to evaluate the levels of total ghrelin, AG and UG in medically naive and treated patients with biochemically active acromegaly, with respect to variables of lipid and glucose metabolism. MATERIAL AND METHODS: We studied total ghrelin, AG and calculated UG levels in a group of 24 patients with active acromegaly and 15 healthy controls. Plasma levels of GH, insulin-like growth factor 1 (IGF-1), insulin, glucose, total cholesterol (TC), high-density lipoprotein (HDL) cholesterol and calculated low-density lipoprotein (LDL) cholesterol, triglycerides (TG), apolipoproteins A1 (APO A1), and B-100 (APO B-100) were measured. RESULTS: Patients with acromegaly revealed lower levels of total ghrelin than healthy controls. In pooled data of all subgroups, simple linear regression analysis revealed that total ghrelin concentration was significantly associated with APO A1 concentration (ß = 0.8087; p = 0.0315) and AG concentration was significantly associated with fasting insulin concentration (ß = 15.5183; p = 0.011). There was an inverse association between UG and the patients' age, and positive association between UG and APO A1. CONCLUSIONS: Our results suggest that ghrelin may influence metabolic disturbances in acromegaly. It seems that the assessment of AG and UG is superior to total ghrelin measurement. Mechanisms regulating ghrelin acylation and function of each form need elucidation in order to improve diagnostics and treatment of metabolic disturbances, not only acromegaly.

Expression of ghrelin and ghrelin functional receptor GHSR1a in human pituitary adenomas.

INTRODUCTION    Pituitary adenomas are heterogenous lesions commonly observed in the central nervous system. Signal transduction of ghrelin, an endogenous ligand specific for growth hormone secretagogue receptor (GHSR), has been reported to be involved in the development of endocrine tumors. However, there are limited data concerning the role of ghrelin and its functional receptor in pituitary adenomas. OBJECTIVES    The aim of the study was to establish the expression pattern of GHRL and its functional receptor GHSR1a in human pituitary adenomas. PATIENTS AND METHODS    Tissue specimens, including somatotropinomas (n = 20), prolactinomas (n = 5), and nonfunctioning adenomas (n = 52) were obtained from 77 patients. Thirteen normal pituitaries served as controls. The expression pattern of GHRL and GHSR1a mRNAs was established using reverse transcription followed by quantitative polymerase chain reaction. RESULTS    Ghrelin mRNA was detected in 92.2% of the samples including controls, while GHSR1a transcripts were detected in 54.4% of the cases. Significant differences were found among subgroups in the GHSR1a expression (P <0.0001) but not in that of GHRL (P = 0.7). The relative GHSR1a expression level was significantly lower for nonfunctioning tumors than for the control group or somatotropinomas. Controls revealed a strong positive correlation between the expression of both genes (r = 0.8; P <0.0001), unlike adenomas, which showed a weak negative correlation (r = -0.3; P >0.05). The maximum tumor diameter for nonfunctioning adenomas was higher than that for somatotropinomas (mean [SD], 31.4 [76] mm vs 24.8 [10.9] mm; P = 0.01). Neither the GHRL nor GHSR1a expression showed a significant correlation with tumor size in the subgroups. CONCLUSIONS    The presence of GHRL and GHSR1a in the neural system indicates their effect on pituitary function regulation and suggests their possible role in adenoma pathogenesis.