Central administration of ghrelin and agouti-related protein (83-132) increases food intake and decreases spontaneous locomotor activity in rats

Ghrelin was recently identified as an endogenous ligand of the GH secretagogue receptor. The novel peptide hormone is produced by gastric A-like cells, and circulating levels rise before feeding, suggestive of ghrelin as an endogenous hunger factor. ghrelin stimulates food intake and promotes adiposity after peripheral or central administration, likely by activating hypothalamic neurons expressing the orexigenic neuropeptides neuropeptide Y (NPY) and agouti-related protein (AGRP). To examine whether ghrelin-induced feeding resembles NPY and AGRP [AGRP fragment (83-132)] induced orexia, we compared the short- and long-term orexigenic capacity of the three peptides. A single intracerebroventricular injection of ghrelin (0.2, 1.0, and 5.0 microg) increased food intake in a dose-dependent manner. A prolonged and uncompensated increase in feeding was seen after the highest dose of ghrelin. The prolonged effects on feeding (+72 h) closely resembled those of AGRP (83-132) but not NPY. Surprisingly, ghrelin injections reduced overall locomotor activity by 20% during the first 24-h observation period. AGRP (83-132) had similar effects on locomotor behavior, whereas NPY had no effect. In summary, ghrelin causes long-term increases of food intake and, like AGRP, plays a previously unknown role as a suppressor of spontaneous physical activity. Expanding the current model of food intake control to include mechanisms regulating physical activity may promote our understanding of two major etiological factors causing obesity.     

Reboxetine acutely stimulates cortisol, ACTH, growth hormone and prolactin secretion in healthy male subjects

In this single-blind study the effects of acute oral administration of the selective noradrenaline reuptake inhibitor reboxetine on the cortisol (COR), ACTH, growth hormone (GH) and prolactin (PRL) secretion were examined in 12 healthy male volunteers. In a randomized order, the subjects received placebo or reboxetine (4 mg) at 0800 h on two different days. After insertion of an intravenous catheter, blood samples were drawn 1 hour prior to the administration of placebo or reboxetine, at time of administration, and during the time of 5 hours thereafter at periods of 30 minutes. Serum concentrations of COR, GH, and PRL as well as plasma levels of ACTH were determined in each blood sample by means of double antibody RIA, fluoroimmunoassay and chemiluminescence immunometric assay methods. The area under the curve (AUC) value was used as parameter for the COR, ACTH, GH, and PRL response. Using t-tests for paired samples, statistical analysis revealed significant stimulatory effects of reboxetine on COR, ACTH, GH, and PRL secretion, compared to placebo (mean AUC values+/-S.E.M. (a) reboxetine: COR 127893.20+/-8125.75 nmol/l x min; ACTH 2385.68+/-387.19 pmol/l x min; GH 56026.59+/-15594.87 pmol/l x min; PRL 113961.60+/-10280.44 pmol/l x min; (b) placebo: COR 83672.19+/-5225.20 nmol/l x min; ACTH 1449.83+/-190.67 pmol/l x min; GH 9308.16+/-3402.75 pmol/l x min; PRL 64663.28+/-7283.62 pmol/l x min). Mean arterial blood pressure and heart rate were significantly increased by reboxetine, too. Our results suggest that besides COR, ACTH and GH secretion, the release of PRL is also under the control of the noradrenergic systems in man.     

Simultaneous determination of seven unconjugated steroids in maternal venous and umbilical arterial and venous serum in elective and emergency cesarean section at term.

In order to assess specific gluco- and mineralocorticoid functions in both mother and fetoplacental unit in relation to the presence or absence of labor, serum levels of unconjugated aldosterone (A), corticosterone (B), deoxycorticosterone (DOC), progesterone (P), 17-hydroxyprogesterone (17-OHP), cortisol (F), and cortisone (E) were determined simultaneously. These levels were determined by specific radioimmunoassays in two groups of 24 paired maternal venous and umbilical arterial and venous samples obtained at term delivery by either elective (Group I, N = 8) or emergency (Group II, N = 8) cesarean section. In Group II, after spontaneous labor, mean maternal serum levels of all steroids investigated exceeded those found in Group I (not in labor). These increases were most pronounced (p less than 0.005) in F (74%) and DOC (106%) levels demonstrating stimulation of both the glucocorticoid (cortisol)--and the mineralocorticoid (aldosterone)--producing pathways of the maternal adrenals by spontaneous labor. Arteriovenous differences in umbilical steroid levels revealed in both groups the placental origin of P, 17-OHP, and E (p less than 0.05 to 0.005), with greater (more negative) mean AV differences after labor (Group II). The negative AV difference of DOC, B, A, and F found in Group I, however, decreased after labor and became even positive in the cases of B and F, reflecting the close relationship between spontaneous labor and the fetal adrenal's active production not only of the glucocorticoids B and F, but also, to a lesser extent, of the mineralocorticoids DOC and aldosterone.     

Doping with growth hormone

Triggered by the Olympic games in Sydney last year, many articles in the press suggested that recombinant human growth hormone (hGH) is one of the most popular performance enhancing drugs used by athletes. However, any hard facts on hGH abuse were provided by Australian customs officers--and not by laboratory assessment. The lack of an official test for hGH doping together with the widespread rumours on its tremendous beneficial effects seem to make this compound attractive for athletes. From a scientific point of view, there are two major questions about this issue: First, as there is no controlled study demonstrating a profound effect of hGH administration on workload capacity in healthy adults, why do athletes use hGH? Second, how could the application of a substance naturally occurring in the human body be detected? Both aspects are discussed in this article.     

The influence of mirtazapine on anterior pituitary hormone secretion in healthy male subjects

RATIONALE: Unlike other antidepressants, mirtazapine does not inhibit the reuptake of norepinephrine or serotonin but acts as an antagonist at presynaptic alpha(2) receptors, at postsynaptic 5-HT(2) and 5-HT(3) receptors, and at histaminergic H(1) receptors. This special mechanism of action may be characterized by a distinct pharmacoendocrinological profile. OBJECTIVES: In the present investigation the influence of acute oral administration of 15 mg mirtazapine on the cortisol (COR), corticotropin (ACTH), growth hormone (GH), and prolactin (PRL) secretion was examined in six healthy male subjects, compared to placebo. METHODS: After insertion of an intravenous catheter, both the mean arterial blood pressure (MAP) and the heart rate were recorded and blood samples were drawn 1 h prior to the administration of mirtazapine or placebo (7:00 a.m.), at time of application (8:00 a.m.), and thereafter every hour up to 8:00 p.m. Concentrations of COR, ACTH, GH, and PRL were measured in each blood sample by double-antibody radioimmunoassay and chemiluminescence immunoassay methods. The area under the curve (AUC) was used as parameter for the COR, ACTH, GH, and PRL response. Furthermore, the urinary free cortisol excretion (UFC) was determined beginning at 8:00 a.m. (time of application of placebo or mirtazapine) up to 8:00 a.m. the day after. RESULTS: Multivariate analyses of variance revealed significantly lower COR AUC, ACTH AUC, and UFC values after 15 mg mirtazapine compared to placebo, whereas no differences were found with respect to GH and PRL stimulation, MAP, and heart rate. CONCLUSIONS: Since the acute inhibition of COR secretion in the healthy volunteers was paralleled by a simultaneous decrease of ACTH release, central mechanisms (for example, inhibition of hypothalamic CRH output) are suggested to be responsible for the inhibitory effects of mirtazapine on COR secretion. Our results are of particular interest in the light of the hypercortisolism observed in depressed patients and new pharmacological approaches such as CRH(1) receptor antagonists.     

Indications, limitations and pitfalls in the determination of human growth hormone, IGF-I and their binding proteins

Deviations from normal growth are a major part of Pediatric Endocrinology. The principal post-natal growth promoting hormones are pituitary growth hormone (GH) and insulin-like growth factor-I (IGF-I). The GH-IGF-I axis has many links and portals, the secrets of which have been disclosed in recent years by scientific advances (genetic and biochemical technologies). In this article, we describe the players in the GH axis, the auxological indications for performing GH evaluation tests, enumerate the most frequently used tests and discuss the laboratory tests which help to define the pathological entities along the GH axis. Emphasis is put on the limitations of methods used, lack of standards, norms and the possible errors in diagnosis and treatment indications that may evolve. As both hGH and IGF-I immunoassay measurements represent cornerstones in the diagnosis and monitoring of the different etiological entities presenting with short stature, clinicians must have an insight into the variability and limitations of these analytical techniques. Interpretation of biochemical results without proper reference data and without knowledge of the assay-inherent characteristics inevitably leads to misdiagnosis, unnecessary further testing and treatment and imposes a burden on the child, family and the health care system.     

Virilization without adrenal hyperplasia in 21-hydroxylase deficiency during fetal life

The characteristic excess production of androgens in the cortisol 21-hydroxylase defect is generally considered to be secondary to ACTH stimulation of alternate pathways. Whenever a morphological examination of the adrenals has been possible in this disorder, adrenocortical hyperplasia was a constant finding. The availability of methods for the prenatal diagnosis of the 21-hydroxylase defect has made it possible to examine some of the manifestations of this disorder during fetal life. We studied a severely virilized 20-week-old aborted female fetus with the 21-hydroxylase defect whose adrenals were neither grossly enlarged nor microscopically hyperplastic. In a pregnancy at risk for congenital adrenal hyperplasia due to a 21-hydroxylase deficiency, amniocentesis was performed in the 18th week of gestation. The 21-hydroxylase defect was established by HLA typing and highly elevated levels of 17-hydroxyprogesterone, testosterone, and androstendione in amniotic fluid. After counselling, the parents, who already had a girl with the salt-wasting form of 21-hydroxylase deficiency, wished termination of the pregnancy. The aborted 20-week-old fetus was within the normal range for gestational age in weight and height. The external genitalia were ambiguous and extremely virilized, with an enlarged clitoris and fused labioscrotal folds. A urogenital sinus opened at the base of the clitoris. The internal organs were female, with a normal uterus and ovaries. Both adrenals were normal in size and weight for their gestational age. Histological examination of the adrenals revealed no abnormalities, and no hyperplasia was detectable. Thus, the adrenals in the 21-hydroxylase defect during fetal life secrete excessive amounts of androgens and cause virilization in the absence of adrenocortical hyperplasia.     

Carbohydrate Content of Post-operative Diet Influences the Effect of Vertical Sleeve Gastrectomy on Body Weight Reduction in Obese Rats

Background

Vertical sleeve gastrectomy (VSG) effectively reduces body weight (BW) in obese rats and humans. However, post-surgical weight regain is frequently observed in subjects after VSG, but the underlying reasons remain poorly understood. We therefore investigated if post-surgical consumption of different diets can affect the outcome of VSG.

Methods

VSG or sham operation was performed in Long–Evans rats with diet-induced obesity (n?=?37). After post-surgical recovery, rats were fed ad libitum either with standard chow (CH), high-fat (HF) or low-carbohydrate, high-fat (LCHF) diets. BW and food intake were measured every second day; serum leptin, cholesterol, HDL cholesterol, and triglycerides were analyzed 4 weeks after surgery. Energy expenditure and locomotor activity were determined by a combined indirect calorimetry system, lean and fat mass by nuclear magnetic resonance.

Results

After 4 weeks, BW gain, fat mass, and leptin were lower in VSG rats when compared to sham controls (p?Conclusion In conclusion, consumption of a HF diet but not the more energy-dense LCHF diet reduced the effectiveness of VSG in rats.     

The relationship between alexithymia and salivary cortisol levels in somatoform disorders

The purpose of this study was to investigate cortisol levels as a function of the hypothalamic–pituitary–adrenal axis (HPA) in relation to alexithymia in patients with somatoform disorders (SFD). Diurnal salivary cortisol was sampled in 32 patients with SFD who also underwent a psychiatric examination and filled in questionnaires (Toronto Alexithymia Scale, TAS scale; Screening for Somatoform Symptoms, SOMS scale; Hamilton Depression Scale, HAMD). The mean TAS total score in the sample was 55.6±9.6, 32% of patients being classified as alexithymic on the basis of their TAS scores. Depression scores were moderate (HAMD=13.2, Beck Depression Inventory, BDI=16.5). The patients’ alexithymia scores (TAS scale “Difficulty identifying feelings”) correlated significantly positively with their somatization scale scores (Symptom Checklist-90 Revised, SCL-90-R); r=0.3438 (P<0.05) and their scores on the Global Severity Index (GSI) on the SCL-90-R; r=0.781 (P<0.01). Regression analysis was performed with cortisol variables as the dependent variables. Cortisol levels [measured by the area under the curve–ground (AUC-G), area under the curve–increase (AUC-I) and morning cortisol (MCS)] were best predicted in a multiple linear regression model by lower depressive scores (HAMD) and more psychopathological symptoms (SCL-90-R). No significant correlations were found between the patients’ alexithymia scores (TAS) and cortisol levels. The healthy control group (n=25) demonstrated significantly higher cortisol levels than did the patients with SFD; in both tests P<0.001 for AUC-G and AUC-I. However, the two groups did not differ in terms of their mean morning cortisol levels (P>0.05). The results suggest that pre-existing hypocortisolism might possibly be associated with SFD.