ACTA ENDOCRINOLOGICA (BUC)

Context. Oxytocin has been investigated as a potential medication for psychiatric disorders. Objective and design. This study prospectively investigates correlations between oxytocin and other neuropeptides plasma levels in patients with autism spectrum disorders (ASD) according to severity and treatment, as compared to controls. Subjects and methods. Thirty-one children (6 neurotypical as control) participated in this study. The patients were classified into mildly and severely-affected, according to Autism Diagnostic Observation Schedule (ADOS) scores. Oxytocin, orexin A and B, α-MSH, β-endorphins, neurotensin and substance P were investigated using a quantitative multiplex assay or a competitive-ELISA method. Results. Plasma oxytocin levels differed between the groups (F (2, 24) =6.48, p=0.006, η2=0.35, observed power=86%): patients with the mild ASD had higher values of plasma oxytocin than those with the severe form (average difference=74.56±20.74pg/mL, p=0.004). Conclusions. These results show a negative correlation between plasma levels of oxytocin and the severity of ASD and support the involvement of oxytocinergic mechanisms in ASD.

Background. Organophosphate exposure induces many endocrine effects. Aim. In this study we observed the effects of acute stress induced by cholinesterase inhibition on the main hormonal axes. Materials and Methods. We included thirteen weanling Wistar rats that were subjected to organophosphate exposure. They were first tested for baseline levels of butyrylcholinesterase, cortisol, free triiodothyronine, thyroxine, thyroid-stimulating hormone and prolactin. Secondly, chlorpyrifos was administered. Next samples were taken to determine the level of all the above-mentioned parameters. Results. Butyrylcholinesterase was significantly decreased after exposure (p<0.001). Cortisol levels were significantly higher after clorpyrifos administration (358.75±43 vs. 241.2±35 nmoL/L)(p<0.01). Although prolactin had a growing trend (450.25±24.65 vs. 423±43.4 uI/mL), the results were not statistically significant. Both free triiodothyronine and thyroxine were significantly higher after exposure. Surprisingly, thyroid-stimulating hormone level almost doubled after exposure with high statistical significance (p<0.001), suggesting a central stimulation of thyroid axis. Butyrylcholinesterase level was proportional with thyroid-stimulating hormone level (p=0.02) and thyroxine level was inversely correlated to the cortisol level (p=0.01). Acute cholinesterase inhibition may induce high levels of cortisol, free triiodothyronine, thyroxine and thyroid-stimulating hormone. From our knowledge this is the first study dedicated to the assessment of acute changes of hormonal status in weanling animals after low-dose organophosphate exposure. Conclusion. Acute cholinesterase inhibition may cause acute phase hormonal disturbances specific to shocked patients.

Melanoma has a significant mortality and its growing incidence is associated with important social and health care costs. Thus, investigation of the complex mechanisms contributing to emergence and development of melanoma are of real interest both in scientific research and clinical practice. Estrogens play an important role in the emergence and development of certain types of cancer, such as breast cancer, endometrial cancer and ovarian cancer, but their role in development of cutaneous melanoma is still a matter of debate. Various data suggest that increased levels of endogenous estrogens during pregnancy or exposure to exogenous estrogens by use of oral contraceptives (OCs) and hormone replacement therapy (HRT) may have a potential role in melanoma development and progression. Moreover, there were revealed several intracellular pathways which can support the connection between estrogens, estrogen receptors (ER) and melanoma. While ER-β plays an antiproliferative role, ER-α promotes cell growth and cellular atypia. Thus, inhibition of ER-β activity in the skin can increase the risk for development of cutaneous melanoma and spread of metastatic cells. However, despite recent advances in this area, the exact role and clinical implications of estrogens and estrogen receptors in melanoma are still not entirely understood and require further investigations

Diabetes is one of the most prevalent chronic disorders, associating numerous somatic and behavioral modifications. Oxytocin has been widely studied for its involvement in social behavior and psychiatric disorders. This pilot study presents a series of 3 patients with type 1 diabetes and diabetic neuropathy in which the values of plasma oxytocin, neurotensin, β-endorphins, α-MSH, substance P and orexin A were measured in comparison to 3 healthy controls with matching ages. In the diabetic patients group, there was a strong negative correlation between the value of plasma glucose and oxytocin (r=-0.99, p=0.04), respectively neurotensin (r=- 0.99, p=0.03). These values did not correlate in the control group. The results suggest that oxytocin, in conjunction with neurotensin, could be investigated as a potential early detection marker of diabetic neuropathy and, to our knowledge, this is the first report focusing on plasma oxytocin levels in patients with diabetic neuropathy.

Context. Melanoma is the most aggressive skin cancer, with significant morbidity and mortality, and one factor that may influence the course of disease is stress. Objective. Our aim was to evaluate the effect of corticosterone, norepinephrine, epinephrine on murine B16F10 melanoma cells in vitro proliferation. Methods. B16F10 melanoma cells were treated with different concentrations of tested hormones. The proliferative capacity of melanoma cells was quantified by MTS assay and the cell viability was quantified as membrane integrity evaluation measured by lactate dehydrogenase (LDH) release. Results. B16F10 cells treated with corticosterone showed no significant changes. In contrast, norepinephrine exposure stimulated the cell proliferation (P = 0.0003). Treatment with 1 μM norepinephrine induced the highest increase in cell proliferation (OD 492 = 0.27 ± 0.02) statistically significant to both control (OD 492 = 0.17 ± 0.01; p = 0.0003), 10 nM norepinephrine (OD 492 = 0.16 ± 0.00; p = 0.0004) and 100 nM norepinephrine (OD 492 = 0.19 ± 0.01; p = 0.002). Likewise, treatment with epinephrine increased cell proliferation (p = 0.0004). Exposure to 5 μm epinephrine induced a stimulation of cell proliferation (OD 492 = 0.28 ± 0.02) significantly higher compared to controls (OD 492 = 0.17 ± 0.01; p = 0.0004), 50 nM epinephrine (OD 492 = 0.17 ± 0.00; p = 0.001) and 500 nM epinephrine (OD 492 = 0.173 ± 0.00; p = 0.001). Conclusions. Our results may open new perspectives concerning the link between stress hormones and melanoma, emphasizing a direct stimulating in vitro effect induced by catecholamines on melanoma B16F10 cells proliferation.

Mixed gonadal dysgenesis and ovotesticular disorders of sex development, are rare conditions that occur sporadically,\r\nwith unknown prevalence. Clinical manifestation of this diseases is sexual ambiguity. The authors present a pediatric\r\ncase with sexual ambiguity and karyotype 45, X/46, XY, the child of a HIV-positive mother receiving multiple antiretroviral treatments for a period of 16 years.