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Biomedical subjects

Carlos Dieguez

Publications and source records attributed to Carlos Dieguez.

At least 19 recordsLinked to original sources
PubMed2007

Obestatin-mediated proliferation of human retinal pigment epithelial cells: regulatory mechanisms.

In this work, we have evaluated the effect of the new discovered peptide obestatin on cell proliferation in primary cultures of human retinal epithelial cells (hRPE cells). The results showed that this peptide induced, in a dose-dependent manner, cell proliferation by MEK/ERK 1/2 phosphorylation. A sequential analysis of the obestatin transmembrane signaling pathway showed that the ERK 1/2 activity is partially blocked after preincubation of the cells with pertussis toxin (PTX), as well as by wortmannin (an inhibitor of PI3K), claphostin C (an inhibitor of PKC), and PP2 (which inhibits the non receptor tyrosine kinase Src). Upon administration of obestatin, the intracellular levels of phospho-PKCepsilon-, theta-, and micro-isoenzymes rise with different time courses, from which PKCepsilon might be responsible for ERK 1/2 response. Based on the experimental data, a signaling pathway involving the consecutive activation of Gi, PI3K, novel PKC (probably PKCepsilon), and Src for ERK 1/2 activation is proposed. These results incorporate a new mitogenic factor to the group of factors that regulate proliferation of hRPE cells.

Cell Count↗
PubMed2006

Regulation of pituitary cell function by adiponectin.

Adiponectin is a member of the family of adipose tissue-related hormones known as adipokines, which exerts antidiabetic, antiatherogenic, antiinflammatory, and antiangiogenic properties. Adiponectin actions are primarily mediated through binding to two receptors expressed in several tissues, AdipoR1 and AdipoR2. Likewise, adiponectin expression has been detected in adipocytes as well as in a variety of extra-adipose tissues, including the chicken pituitary. Interestingly, adiponectin secretion and adiponectin receptor expression in adipocytes have been shown to be regulated by pituitary hormones. These observations led us to investigate whether adiponectin, like the adipokine leptin, regulates pituitary hormone production. Specifically, we focused our analysis on somatotrophs and gonadotrophs because of the relationship between the control of energy metabolism, growth and reproduction. To this end, the effects of adiponectin on both GH and LH secretion as well as its interaction with major stimulatory regulators of somatotrophs (ghrelin and GHRH) and gonadotrophs (GnRH) and with their corresponding receptors (GHS-R, GHRH-R, and GnRH-R), were evaluated in rat pituitary cell cultures. Results show that adiponectin inhibits GH and LH release as well as both ghrelin-induced GH release and GnRH-stimulated LH secretion in short-term (4 h) treated cell cultures, wherein the adipokine also increases GHRH-R and GHS-R mRNA content while decreasing that of GnRH-R. Additionally, we demonstrate that the pituitary expresses both adiponectin and adiponectin receptors under the regulation of the adipokine. In sum, our data indicate that adiponectin, either locally produced or from other sources, may play a neuroendocrine role in the control of both somatotrophs and gonadotrophs.

Adiponectin↗
PubMed2006

One ancestor, several peptides post-translational modifications of preproghrelin generate several peptides with antithetical effects.

Preproghrelin is the polypeptide precursor of ghrelin. First discovered in gastric extract as a growth hormone releasing peptide and food intake modulator, it has more recently been revealed to have other physiological aspects. The fine molecular mechanisms of ghrelin biosynthesis show that this peptide is but one piece of a puzzle which contains many other peptides obtained from alternative splicing of the same gene or from extensive post-translational modifications. Recent developments have shown that pro-ghrelin cleavage generates another active peptide named obestatin with an intriguingly subtle but opposite physiological action to ghrelin. Noteworthy, and similar to ghrelin, which requires post-translational processing close to its amino terminus by acylation, the biological activity of the ghrelin-associated peptide obestatin also depends on modification, but by amidation at its carboxyl terminus. In this review we will summarize the steps which led to the identification of pre-proghrelin gene products and will examine the significance and perspectives of the different peptides generated from the same ancestor gene.

Animals↗
PubMed2006

Effect of obesity and morbid obesity on the growth hormone (GH) secretion elicited by the combined GHRH + GHRP-6 test.

OBJECTIVE: Obesity is characterized by low basal levels of growth hormone (GH) and impeded GH release. However, the main problem arises in the diagnosis of GH deficiency in adults, as all accepted cut-offs in the diagnostic tests of GH reserve are no longer valid in obese subjects. In this work, the role of obesity in the GH response elicited by the GHRH + GHRP-6 test was assessed in a large population of obese and nonobese subjects. PATIENTS: GHRH + GHRP-6-induced GH peaks were evaluated in 542 subjects. One hundred and five were healthy obese, 50 were morbid obese, and 261 were nonobese (both normal weight and overweight). One hundred and seventy-six GH-deficient patients (obese and nonobese) were also studied. RESULTS: A regression analysis of the 366 subjects with normal pituitary function indicated that adiposity had a negative effect on the elicited GH peak (r = -0.503, P < 0.0001). A receiver operating characteristic (ROC) curve analysis showed that in subjects with a BMI < or =35, the currently accepted cut-offs of the GHRH + GHRP-6 test (GH peaks > or =20 microg/l: normal secretion; GH peaks < or =10 microg/l: GH deficiency), were fully operative. However, in subjects with a BMI > 35, normality was indicated by GH peaks > or =15 microg/l and GH deficiency by peaks < or =5 microg/l (1 microg/l = 2.6 mU/l). CONCLUSIONS: This study confirms: (a) that the combined provocative test is adequate to separate normal and GH-deficient subjects; (b) the negative effect of obesity on GH secretion; (c) that obesity accounts for 25% of the reduction of GH release; and (d) that present cut-off values are applicable to normal weight, overweight and grade I obesity subjects, whereas in obese subjects with a BMI exceeding 35, all the normative limits of the GHRH-GHRP +6 test must be reduced by 5 microg/l.

Adolescent↗
PubMed2006

Circulating hormones and hypothalamic energy balance: regulatory gene expression in the Lou/C and Wistar rats.

To ascertain the mechanisms underlying low caloric intake and low body weight in the Lou/C rat, the circulating hormone levels and gene expression of hypothalamic peptides and receptors important in energy balance and the induction of suppressor of cytokine signalling 3 (SOCS3) gene expression in response to leptin challenge were compared with Wistar rats. Plasma leptin levels were lower in the Lou/C rat, as were levels of rat corticosterone, TSH and T4 but not T3. Ghrelin levels were higher in the Lou/C rat. Total leptin receptor (Ob-R) and the long form of the leptin receptor (Ob-Rb) gene expression were lower in the arcuate (ARC) and ventromedial nuclei (VMN) in Lou/C rat. Ghrelin receptor expression in the ARC and VMN was lower in Lou/C than in Wistar rats. However, agouti gene-related peptide (AgRP) and neuropeptide Y (NPY) gene expression were higher in the Lou/C rat. There was no difference in the level of cocaine- and amphetamine-regulated transcript gene expression in the ARC, but both were higher in the paraventricular nuclei of the Lou/C breed. There was no difference in Ob-R gene expression in, or [(125)I]leptin binding to, the choroid plexus. SOCS3 mRNA induction in response to leptin was lower in the Lou/C rat. This study reveals that the comparatively low plasma leptin, TSH and T4 levels, and high ghrelin levels together with high levels of AgRP and NPY gene expression seen in the Lou/C rat are indicative of a strong drive to eat and decreased energy expenditure, which are in direct opposition to the comparatively low body weight and adiposity of this rat strain.

Agouti-Related Protein↗
PubMed2006

Negative energy balance and leptin regulate neuromedin-U expression in the rat pars tuberalis.

Central neuromedin U (NMU) functions in energy balance, the hypothalamic-pituitary-adrenal axis, LH release and circadian rhythmicity. In rats, high levels of NMU occur in the hypothalamic suprachiasmatic nuclei and the pars tuberalis of the pituitary. NMU expression in the pars tuberalis appears to be downregulated in the Zucker fatty (fa/fa) rat, lacking functional leptin receptors. In contrast, in the dorsomedial (DMH) nuclei of the mouse, NMU expression is higher in the ob/ob mouse, lacking leptin, and is upregulated by fasting. However, leptin appears not to change NMU gene expression in either the mouse DMH or the rat pars tuberalis. Thus, the present study aims to better identify factors influencing central NMU expression in the rat pars tuberalis. Sprague-Dawley rats were fasted and/or challenged with intracerebroventricular leptin or ghrelin and gene expression was measured using real-time reverse transcriptase-PCR and quantitative in situ hybridisation with riboprobes specific for NMU and NMU receptor (NMU-R2). NMU expression in the rat pars tuberalis was elevated by fasting. Ghrelin administration had no effect on the level of NMU expression, but leptin was found to diminish the expression in a concentration- and time-dependent manner. NMU-R2 expression was unchanged in any of the groups measured. These results suggest that NMU expression in rat pars tuberalis is upregulated in states of negative energy balance, and this may be mediated indirectly by changes in leptin levels. These results demonstrate a link between energy balance and NMU expression in the pars tuberalis of the pituitary.

Animals↗
PubMed2006

Expression of hypothalamic KiSS-1 system and rescue of defective gonadotropic responses by kisspeptin in streptozotocin-induced diabetic male rats.

Hypogonadotropism is a common feature of uncontrolled diabetes, for which the ultimate mechanism remains to be elucidated. Kisspeptins, ligands of G protein-coupled receptor 54 (GPR54) encoded by the KiSS-1 gene, have recently emerged as major gatekeepers of the gonadotropic axis. Alteration in the hypothalamic KiSS-1 system has been reported in adverse metabolic conditions linked to suppressed gonadotropins, such as undernutrition. However, its potential contribution to defective gonadotropin secretion in diabetes has not been evaluated. We report herein analyses of luteinizing hormone (LH) responses to kisspeptin and hypothalamic expression of the KiSS-1 gene in streptozotocin (STZ)-induced diabetic male rats. In addition, functional studies involving kisspeptin replacement or continuous administration of leptin and insulin to diabetic male rats are presented. Kisspeptin administration evoked robust LH and testosterone bursts and enhanced postgonadectomy LH concentrations, despite prevailing attenuation of gonadotropic axis in diabetic animals. In addition, hypothalamic KiSS-1 mRNA levels were unambiguously decreased in diabetic male rats, and the postorchidectomy rise in KiSS-1 mRNA was severely blunted. Repeated administration of kisspeptin to diabetic rats evoked persistent LH and testosterone responses and partially rescued prostate and testis weights. In addition, central infusion of leptin, but not insulin, was sufficient to normalize hypothalamic KiSS-1 mRNA levels, as well as LH and testosterone concentrations. In summary, we provide evidence for altered expression of the hypothalamic KiSS-1 system in a model of uncontrolled diabetes. This observation, together with the ability of exogenous kisspeptin to rescue defective LH responses in diabetic rats, unravel the physiopathological implication, and potential therapeutic intervention, of the KiSS-1 system in altered gonadotropin secretion of type 1 diabetes.

Animals↗
PubMed2005

Leptin, from fat to inflammation: old questions and new insights.

Leptin is 16 kDa adipokine that links nutritional status with neuroendocrine and immune functions. Initially thought to be a satiety factor that regulates body weight by inhibiting food intake and stimulating energy expenditure, leptin is a pleiotropic hormone whose multiple effects include regulation of endocrine function, reproduction, and immunity. Leptin can be considered as a pro-inflammatory cytokine that belongs to the family of long-chain helical cytokines and has structural similarity with interleukin-6, prolactin, growth hormone, IL-12, IL-15, granulocyte colony-stimulating factor and oncostatin M. Because of its dual nature as a hormone and cytokine, leptin links the neuroendocrine and the immune system. The role of leptin in the modulation of immune response and inflammation has recently become increasingly evident. The increase in leptin production that occurs during infection and inflammation strongly suggests that leptin is a part of the cytokine network which governs the inflammatory-immune response and the host defense mechanisms. Leptin plays an important role in inflammatory processes involving T cells and has been reported to modulate T-helper cells activity in the cellular immune response. Several studies have implicated leptin in the pathogenesis of autoimmune inflammatory conditions, such as experimental autoimmune encephalomyelitis, type 1 diabetes, rheumatoid arthritis, and intestinal inflammation. Very recently, a key role for leptin in osteoarthritis has been demonstrated: leptin indeed exhibits, in concert with other pro-inflammatory cytokines, a detrimental effect on articular cartilage by promoting nitric oxide synthesis in chondrocytes. Here, we review the recent advances regarding leptin biology with a special focus on those actions relevant to the role of leptin in the pathophysiology of inflammatory processes and immune responses.

Animals↗
PubMed2005

Low plasma ghrelin level in gastrectomized patients is accompanied by enhanced sensitivity to the ghrelin-induced growth hormone release.

Ghrelin is a brain-gut peptide with potent GH-releasing activities. It has been suggested that the majority of circulating ghrelin originates from the stomach, with a smaller portion from the small intestine. Gastrectomy (GASTRX) significantly reduces circulating ghrelin concentrations. The implication of decreased circulating ghrelin on the somatotropic axis post GASTRX has not been studied. Therefore, we aimed to investigate the somatotropic axis in 10 gastrectomized patients who underwent total GASTRX for various reasons at least 2 yr ago. At baseline circulating total ghrelin, GH, IGF-I, and IGF binding protein (IGFBP)-3 levels were measured. The GH stimulation test consisted of an insulin-induced hypoglycemia, ghrelin in two iv bolus doses (0.1 and 1 microg/kg), and a GHRH test. GH sensitivity was assessed by an IGF-I generation test. All the tests were performed 2 wk apart. At baseline serum ghrelin levels were reduced by 55% in GASTRX patients, compared with the control group (P < 0.05). IGF-I (P < 0.05) and IGFBP-3 (P < 0.01) levels were also significantly lower than in controls. GH response to the insulin-induced hypoglycemia test in both GASTRX and control subjects was of similar magnitude, whereas circulating plasma ghrelin levels in GASTRX patients were not modified during hypoglycemia. Both doses (0.1 and 1.0 microg/kg) of ghrelin stimulated GH release significantly more in GASTRX than control subjects, respectively (peak mean GH +/- se: 18.2 +/- 5.6 vs. 5.4 +/- 1.3 microg/liter, P < 0.03; and 58.7 +/- 7.5 vs. 35.3 +/- 1.9 microg/liter, P < 0.01). There was no difference in GHRH-induced GH response between GASTRX patients and control subjects (P > 0.05). Concomitantly, increased increments in IGF-I and IGFBP-3 to a single bolus of GH were found (P < 0.03). In conclusion, our data suggest that low circulating ghrelin levels, found in GASTRX patients, are accompanied by enhanced ghrelin sensitivity with respect to GH response. This is associated with increased GH responsiveness. GASTRX is a state of acquired chronic hypoghrelinemia that may require replacement with ghrelin, and it is tempting to speculate that this may affect the GH-IGF-IGFBP axis.

Adult↗
PubMed2005

Hypopituitarism and growth hormone deficiency in adult subjects after traumatic brain injury: who and when to test.

Traumatic brain injury (TBI) was traditionally considered an infrequent cause of hypopituitarism. However recent reports strongly suggest that TBI-mediated pituitary hormones deficiency may well be more frequent than previously thought. As the prevalence of hypopituitarism is not dependent on the severity of the trauma and considering the high number of TBI events in all industrialized countries a screening procedure for detecting hormone deficiencies in all TBI patients is not possible. In the present work a suggestion for screening a subgroup of TBI patients is discussed in order to increase the effectiveness of the whole procedure.

Brain Injuries↗
PubMed2005

Ghrelin, the same peptide for different functions: player or bystander?

Ghrelin is a recently discovered brain-gut peptide with two main physiological actions: growth hormone secretagogue activity and food intake inducer. Although its production is prevalently gastric, ghrelin is widely expressed in several tissues, where it might therefore act as a paracrine or autocrine factor. It is becoming clear that ghrelin is much more than a simple growth hormone secretagogue. In addition to its formerly envisaged role, ghrelin has other activities including stimulation of pituitary hormones secretion, modulation of food intake and control of energy metabolism, regulation of gastric and pancreatic activity, and cardiovascular and hemodynamic activities. In addition, modulation of cartilage and bone homeostasis, sleep and behavioral influences, and modulation of the immune system, as well as effects on cell proliferation, are other relevant actions of ghrelin. Thus, the peptide appears to be an important component of an integrated multifaceted regulatory system. In this review, we summarize several aspects of ghrelin biology and attempt to inform the reader with information regarding unexpected functions of this gastric peptide.

Acylation↗
PubMed2005

Prevalence of hypopituitarism and growth hormone deficiency in adults long-term after severe traumatic brain injury.

OBJECTIVE: Traumatic brain injury (TBI) has been associated with hypopituitarism and GH deficiency. However, TBI-mediated hypopituitarism may be more frequent than previously thought. The present work, performed in patients with severe TBI at least 1 year before, had three aims: (i) to evaluate the prevalence of hypopituitarism, (ii) in particular to evaluate the prevalence of GH deficiency, and (iii) to compare three different tests of GH reserve in this cohort. DESIGN AND PATIENTS: From a nonselected group of 249 patients admitted to our Clinical Centre for severe TBI over the last 5 years, 200 of them answered a custom made questionnaire of symptoms of hypopituitarism enclosed in the invitation letter to participate in the study. A total of 170 (99 men and 14 women), accepted to participate in the study (study cohort); 57 had normal questionnaires and were not further studied, 14 discontinued the study, and 99 attended the hospital for dynamic tests of pituitary hormone deficiencies. From these, 44 subjects with IGF-I in the lower range were tested with GHRH+GHRP-6; ITT; and glucagon tests of GH reserve, on three different occasions. MEASUREMENTS: Pituitary hormones plus IGF-I and target gland hormones were analysed. RESULTS: With regard to the initial cohort of 170 subjects (100%), three (1.7%) showed diabetes insipidus; 10 (5.8%) TSH deficiency, 11 (6.4%) ACTH deficiency and 29 (17%) gonadotrophin deficiency. In 10 subjects (5.8%), GH deficiency was diagnosed by strict criteria. Finally, 15 (8.8%) showed combined deficit of several hormones. CONCLUSION: After severe head trauma, gonadotrophin deficiency was the most common pituitary deficit. GH deficiency showed a prevalence similar to ACTH and TSH deficits, i.e. near 6% of the cohort. Taken together, 24.7% of the subjects studied showed any type of pituitary hormone deficiency.

Adult↗
PubMed2005

The GHRH/GHRP-6 test for the diagnosis of GH deficiency in elderly or severely obese men.

OBJECTIVE AND DESIGN: Ageing and obesity result in decreased activity of the GH/IGF-I axis and concomitant impaired GH responses to secretory stimuli. We therefore determined the validity of the GH cut-off value of 15.0 microg/l in the GH-releasing hormone (GHRH)/GH releasing peptide-6 (GHRP-6) test for the diagnosis of GH deficiency in elderly or severely obese men. METHODS: We performed a combined GHRH/GHRP-6 test in ten elderly men (mean age 74 years; mean body mass index (BMI) 24.6 kg/m(2)), nine obese men (mean age 47 years; mean BMI 40.6 kg/m(2)) and seven healthy male controls (mean age 51 years, mean BMI 24.3 kg/m(2)). After assessment of fasting plasma GH, IGF-I and IGF-binding protein-3 (IGFBP-3), GHRH (100 microg) and GHRP-6 (93 microg) were given intravenously as a bolus injection. Repeated GH measurements were performed for two hours. RESULTS: Both peak GH levels and areas under the curve (AUC) were significantly lower in the obese than in the controls (peak 13.2 vs 53.4 microg/l, P = 0.001; AUC 707 vs 3250 microg/l x 120 min; P = 0.001). Mean GH response in the elderly was lower than in the controls (peak 35.0 microg/l; AUC 2274 microg/l x 120 min), but this was not statistically significant. In contrast, GH peak levels in seven obese men remained below the cut-off level of 15.0 microg/l associated with severe GH deficiency. All others had GH peak levels exceeding this threshold. IGFBP-3 levels were significantly lower in the elderly than in the controls (1.35 vs 2.05 mg/l, P = 0.001). Baseline GH or IGF-I did not differ significantly between groups. CONCLUSIONS: GH responses following GHRH/GHRP-6 administration were significantly reduced in severely obese men, but were not significantly reduced in elderly men, despite a negative trend. Our data indicate that the cut-off GH level of 15.0 microg/l after GHRH + GHRP-6 administration for the diagnosis of severe GH deficiency cannot be used in severely obese men.

Aged↗
PubMed2004

Dual action of adiponectin on insulin secretion in insulin-resistant mice.

Adiponectin is secreted by adipocytes and has been implicated as a mediator of insulin sensitivity. In this study, the acute effects of adiponectin on islets isolated from normal or diet-induced insulin resistant mice were examined. In normal islets, adiponectin (5 microg/ml) had no significant effect on insulin secretion. In contrast, in islets from mice rendered insulin resistant by high-fat feeding, adiponectin inhibited insulin secretion at 2.8 mM (P < 0.01) but augmented insulin secretion at 16.7 mM glucose (P < 0.05). The augmentation of glucose-stimulated insulin secretion by adiponectin was accompanied by increased glucose oxidation (P < 0.005), but without any significant effect on palmitate oxidation or the islet ATP/ADP ratio. Furthermore, RT-PCR revealed the expression of the adiponectin receptor AdipoR1 mRNA in mouse islets, however, with no difference in the degree of expression level between the two feeding groups. The results thus uncover a potential dual role for adiponectin to modify insulin secretion in insulin resistance.

Adiponectin↗
PubMed2004

Growth hormone response to GHRH + GHRP-6 in type 2 diabetes during euglycemic and hyperglycemic clamp.

The aim of this study was to investigate the effect of two different glucose levels on GH response to the combined administration of GHRH+GHRP-6 in patients with type 2 diabetes. GH response to i.v. bolus of GHRH+GHRP-6 (100 mcg, each) was measured in 12 male patients with type 2 diabetes (mean age: 53.9+/-1.59 years; BMI: 25.58+/-0.39 kg/m(2); mean HbA(1c): 8.7+/-0.42%), during a euglycemic (mean glucose: 4.92+/-0.08 mmol) hyperinsulinemic clamp (insulin infusion rate of 100 mU/kg/h) and a hyperglycemic clamp (mean glucose: 12.19+/-0.11 mmol/l). There was no difference in basal GH levels between the hyperglycemic and euglycemic clamps (2.9+/-0.99 mU/l versus 1.48+/-0.44 mU/l; P>0.05). Peak GH response to GHRH+GHRP-6 during the hyperglycemic clamp was lower than in the englycemic clamp (112.45+/-14.45 mU/l versus 151.06+/-16.87 mU/l; P<0.05). Area under the GH curve was lower in the hyperglycemic than in the euglycemic clamp (6974.49+/-1001.95 mU/l/min versus 9560.75+/-1140.65 mU/l/min; P<0.05). It is concluded that hyperglycemia significantly reduces GH response to combined administration of GHRH+GHRP-6 in normal weight patients with type 2 diabetes. It is suggested that ambient glucose levels should be taken into account during interpretation of GH response to combined administration of GHRH+GHRP-6 in patients with type 2 diabetes.

Diabetes Mellitus, Type 2↗
PubMed2004

Growth hormone (GH) peaks versus areas under the curve in the diagnosis of adult GH deficiency: analysis of the variables provided by the GHRH + GHRP-6 test.

BACKGROUND: The diagnosis of growth hormone deficiency (GHD) relies on provocative tests of GH reserve. The aim in these tests is to obtain an objective, biochemical-based, measure of gland function, but clinicians and researchers rely on the GH peak, as a surrogate of the 24-hour pituitary secretion. However, on a mathematical basis the area under the secretory curve (AUC) should be more valid for this evaluation. OBJECTIVES: To validate which variable provided by a provocative test of GH secretion is mathematically more robust for supporting the clinical diagnosis. Adult normal subjects and GHD patients were challenged with the combined stimulus GHRH + GHRP-6. The diagnostic efficacy of the GH peak, and the AUC were compared by the receiver operating characteristic (ROC) curve methodology. PATIENTS AND METHODS: 146 patients with GH deficiency due to organic pituitary disease and 184 healthy subjects were administered GHRH 1 microg/Kg iv, plus GHRP-6 1 microg/Kg iv, and GH was determined. Four variables were studied: (a) the GH peak; (b) the "standard" AUC, (c) the "stimulated" AUC and (d) the basal value, used as internal control. RESULTS: Under ROC curve analysis, the basal variable was devoid of diagnostic capability, while the other variables performed strikingly well, the ROC curve area for the GH peak was 0.9997; and for the AUC 0.9993, with no statistical differences. CONCLUSIONS: The variables provided by measuring the GH peak and the area under the curve were similarly effective for diagnosis, although on clinical grounds, the peak was more convenient as needed no calculation. If results for other test were similar the time-honored method of measuring the GH peak could be considered mathematically validated.

Adult↗
PubMed2004

Evaluation of the reproducibility of the GHRH plus GHRP-6 test of growth hormone reserve in adults.

BACKGROUND: The diagnosis of GH deficiency (GHD) is controversial, relying on GH secretion elicited by the provocative tests of GH reserve. However, the performance of most of the tests in use have not been evaluated rigorously. The repeatability of a test is a prerequisite before evaluating its diagnostic capability. OBJECTIVE: The combined administration of GH-releasing hormone (GHRH) and GH-releasing hexapeptide (GHRP-6) is an efficacious test of GH reserve in adults, and the target of this work was to evaluate its reproducibility. METHODS: Seventeen healthy subjects were challenged with GHRH plus GHRP-6 (1 micro g/kg i.v.). All subjects underwent four tests on different days separated by at least 2 months. GH peaks were evaluated by several mathematical analyses of reproducibility. RESULTS: As a group, the subjects showed high reproducibility after the four tests, with GH peaks of 46.0 +/- 5.1; 48.4 +/- 6.4; 50.1 +/- 5.4 and 52.9 +/- 5.8 micro g/l, respectively (1 micro g/l = 3 mU/l). Individually analysed, the reproducibility was good, and the regression analysis showed a correlation between tests 1 and 2 of R = 0.729, P < 0.0009, between tests 1 and 3 of R = 0.710, P < 0.001, and between tests 1 and 4 of R = 0.683, P < 0.002. Under mathematical analysis, the multiple correlation coefficient analysis, analysis of variance (anova) with repeated measurements, repeatability index, the simplest coefficient of variation and the intraclass correlation coefficient (ICC) all unambiguously showed that the GHRH + GHRP-6 test was reproducible. Furthermore, the repeated tests did not alter the biochemical diagnosis of the subjects, with absence of false-positive values. CONCLUSIONS: The GHRH + GHRP-6 test of GH reserve is reproducible in adult subjects.

Adult↗