Ghrelin in human medullary thyroid carcinomas.

OBJECTIVE: Ghrelin is a novel gastrointestinal hormone involved in several metabolic functions. It has been identified previously in several normal and tumoral neuroendocrine tissues, including human medullary thyroid carcinomas (MTCs). The aim of the study was to evaluate ghrelin levels in patients with MTC and nontoxic goitre (NTG) with elevated calcitonin (CT) levels, as an additional marker of the disease. PATIENTS AND DESIGN: The study included 22 patients with MTC (four before and 18 after thyroidectomy), 12 patients with NTG with basal CT levels exceeding 10 ng/l and 15 healthy subjects matched for age, sex and body mass index (BMI). After thyroidectomy, MTC patients were considered cured when basal and pentagastrin-stimulated CT levels were < 0.2 and < 10 ng/l, respectively. A pentagastrin-induced CT peak over 50 ng/l was considered as an abnormal response while 100 ng/l was the cut-off accepted for the diagnosis of C-cell hyperplasia or tumour. Circulating ghrelin and CT levels were evaluated at baseline in patients and controls and at -10, 0, 1, 2, 5 and 15 min after pentagastrin injection (0.5 microg/kg body weight) in 12 patients with MTC and nine with NTG. Four surgically removed MTCs were tested for ghrelin expression. MEASUREMENTS: Total plasma ghrelin and CT levels were measured with a commercially available radioimmunoassay (RIA) and two-site chemiluminescence immunometric assays, respectively. In paraffin-embedded MTC samples ghrelin immunostaining was performed with a polyclonal antibody (1:1000) and the reaction visualized by an indirect immunoperoxidase system. RESULTS: Plasma ghrelin levels found in cured or not cured MTC and in NTG patients were similar to those of BMI-matched healthy controls. No correlation between ghrelin and CT levels, thyroid disease or previous thyroidectomy was observed. The administration of pentagastrin caused a 17% increase in ghrelin levels (basal ghrelin vs. peak: 162 +/- 62 pmol/l vs. 189 +/- 58 pmol/l, P < 0.05) that was particularly evident (33% increase) in patients with an abnormal CT response to the test (CT > 50 ng/l). Immunohistochemistry showed positivity for ghrelin in a small proportion of CT positive cells from the four MTCs removed. CONCLUSIONS: Patients with MTC, NTG and controls showed similar ghrelin levels, ruling out this parameter as a marker of MTC. The increase in ghrelin levels in patients with a positive CT response to pentagastrin, together with the immunopositivity for ghrelin in some MTC cells, suggests C cells as minor source of ghrelin production.

Circulating levels of inhibin A, inhibin B and activin A in normal and intrauterine growth restricted (IUGR) fetuses.

OBJECTIVE: To evaluate the relationships between circulating levels of inhibin A, inhibin B and activin A, and sex, gestational age and gonadotropins in normal and pathological fetuses. STUDY DESIGN: The study included 31 normal fetuses and 12 affected with intrauterine growth restriction (IUGR) of gestational age ranging 20-40 weeks. RESULTS: No gender difference in inhibin A and activin A levels were observed. Inhibin B levels were significantly higher in males than in females (P < 0.05). Fetuses with the highest levels of inhibin A and B were found in the IUGR group that also showed activin A levels significantly higher than normal. No correlations were observed between inhibin A, inhibin B, activin A and both gonadotropins. CONCLUSION: Plasma inhibin A, inhibin B and activin A are detectable in both genders during intrauterine life. The different gender pattern of inhibin B suggests that inhibin B may contribute to the assessment of the hypothalamic-pituitary-gonadal set-point at least in males.

Activin A serum levels and aging of the pituitary-gonadal axis: a cross-sectional study in middle-aged and elderly healthy subjects.

Aim of the study was to investigate activin A serum concentration in healthy adult males and post-menopausal females over a wide age-range and its correlation to gonadotropins, inhibin B and testosterone concentrations. The study included 73 males (aged 30-101 years) and 42 postmenopausal females (aged 50-104 years). Blood samples were collected after an overnight fast to measure serum activin A, inhibin B, LH, FSH, and gonadal steroid levels. A significant increase in serum activin A levels over age in both genders, especially in the oldest age-groups, was observed. Serum inhibin B and testosterone concentrations showed a sharp decrease in male subjects, reflecting the age-related decrease of testicular function and by consequence serum FSH and LH significantly increased. In female subjects LH and FSH levels were very high in subjects in their 50s and showed a continuous decline due to pituitary aging. Simple and multivariable regression analyses demonstrated the lack of correlation between activin A and FSH in both males and females. In conclusion, a steep increase in activin A levels is present during aging in both genders, especially in the last decades of life. The physiologic role and site of production of activin A in old subjects remain to be clarified.

Immunostimulating effect of oral glutamine.

Glutamine represents the principal metabolic substrate for all rapidly proliferating cells. Since part of the glutamine efficacy could be related to immunoregulating properties, we assessed the effects of orally administered glutamine on serum interleukin-2 (IL-2) levels and intestinal T-cell populations in 48 athymic (nude) mice. Twenty-four mice received a standard diet enriched by glutamine (added to drinking water at a 4% concentration), while the other 24 served as the control group and received the same diet without glutamine. In glutamine-fed animals, we observed a marked increase in IL-2 concentrations after 10 days of treatment in comparison with control group and a modest but significant increase in intestinal T-cell counts. These results suggest that oral glutamine is able to exert local and systemic immunostimulating activity that could be of relevance in the prevention of gut integrity and immune defense loss associated, for example, with trauma, surgery, and starvation.