Pinealectomy Increases and Exogenous Melatonin Decreases Leptin Production in Rat Anterior Pituitary Cells: an Immunohistochemical Study

Summary Melatonin, the main hormone of the pineal gland, informs the body about the environmental light and darkness regimen, which in turn contributes to the photoperiodic adaptation of several physiological functions. Leptin, the hormone secreted mainly by adipocytes and some other tissues including the pituitary, informs the brain about the mass of adipose tissue, which plays an important role in energy homeostasis. Melatonin has been shown to decrease circulating leptin levels. It is currently not known whether melatonin has an effect on leptin synthesis in the pituitary. The aim of this study was to immunohistochemically examine the effects of pinealectomy and administration of melatonin on leptin production in the rat anterior pituitary. The pituitary samples obtained from 18 male Wistar rats including sham-pinealectomized, pinealectomized and melatonin-injected pinealectomized groups were immunohistochemically evaluated. Immunostaining of leptin was moderate (3+) in sham-pinealectomized rats, heavy (5+) in pinealectomized rats and low (1+) in melatonin-treated pinealectomized rats, respectively. The present results indicate that pinealectomy induces leptin secretion in anterior pituitary cells, and this increase of leptin synthesis can be prevented by administration of melatonin. Thus, melatonin seems to have both physiological and pharmacological effects on leptin production in the anterior pituitary of male rats

Criteria for the definition of Pituitary Tumor Centers of Excellence (PTCOE): A Pituitary Society Statement

Introduction With the goal of generate uniform criteria among centers dealing with pituitary tumors and to enhance patient care, the Pituitary Society decided to generate criteria for developing Pituitary Tumors Centers of Excellence (PTCOE). Methods To develop that task, a group of ten experts served as a Task Force and through two years of iterative work an initial draft was elaborated. This draft was discussed, modified and finally approved by the Board of Directors of the Pituitary Society. Such document was presented and debated at a specific session of the Congress of the Pituitary Society, Orlando 2017, and suggestions were incorporated. Finally the document was distributed to a large group of global experts that introduced further modifications with final endorsement. Results After five years of iterative work a document with the ideal criteria for a PTCOE is presented. Conclusions Acknowledging that very few centers in the world, if any, likely fulfill the requirements here presented, the document may be a tool to guide improvements of care delivery to patients with pituitary disorders. All these criteria must be accommodated to the regulations and organization of Health of a given country

Twelve-year trends in the prevalence and risk factors of diabetes and prediabetes in Turkish adults

There is concern about an emerging diabetes epidemic in Turkey. We aimed to determine the prevalence of diagnosed and undiagnosed diabetes, prediabetes and their 12-year trends and to identify risk factors for diabetes in the adult Turkish population. A cross-sectional, population-based survey, ‘TURDEP-II’ included 26,499 randomly sampled adults aged ≥ 20 years (response rate: 87 %). Fasting glucose and biochemical parameters were measured in all; then a OGTT was performed to identify diabetes and prediabetes in eligible participants. The prevalence of diabetes was 16.5 % (new 7.5 %), translating to 6.5 million adults with diabetes in Turkey. It was higher in women than men (p = 0.008). The age-standardized prevalence to the TURDEP-I population (performed in 1997–98) was 13.7 % (if same diagnostic definition was applied diabetes prevalence is calculated 11.4 %). The prevalence of isolated-IFG and impaired glucose tolerance (IGT), and combined prediabetes was 14.7, 7.9, and 8.2 %, respectively; and that of obesity 36 % and hypertension 31.4 %. Compared to TURDEP-I; the rate of increase for diabetes: 90 %, IGT: 106 %, obesity: 40 % and central obesity: 35 %, but hypertension decreased by 11 % during the last 12 years. In women age, waist, body mass index (BMI), hypertension, low education, and living environment; in men age, BMI, and hypertension were independently associated with an increased prevalence of diabetes. In women current smoking, and in men being single were associated with a reduced risk. These results from one of the largest nationally representative surveys carried out so far show that diabetes has rapidly become a major public health challenge in Turkey. The figures are alarming and underscore the urgent need for national programs to prevent diabetes, to manage the illness and thus prevent complications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10654-013-9771-5) contains supplementary material, which is available to authorized users

Effects of acute hypoxia on the determination of anaerobic threshold using the heart rate-work rate relationships during incremental exercise tests. Physiol Res

Summary Anaerobic threshold which describes the onset of systematic increase in blood lactate concentration is a widely used concept in clinical and sports medicine. A deflection point between heart rate-work rate has been introduced to determine the anaerobic threshold non-invasively. However, some researchers have consistently reported a heart rate deflection at higher work rates, while others have not. The present study was designed to investigate whether the heart rate deflection point accurately predicts the anaerobic threshold under the condition of acute hypoxia. Eight untrained males performed two incremental exercise tests using an electromagnetically braked cycle ergometer: one breathing room air and one breathing 12 % O 2 . The anaerobic threshold was estimated using the V-slope method and determined from the increase in blood lactate and the decrease in standard bicarbonate concentration. This threshold was also estimated by in the heart rate-work rate relationship. Not all subjects exhibited a heart rate deflection. Only two subjects in the control and four subjects in the hypoxia groups showed a heart rate deflection. Additionally, the heart rate deflection point overestimated the anaerobic threshold. In conclusion, the heart rate deflection point was not an accurate predictor of anaerobic threshold and acute hypoxia did not systematically affect the heart rate-work rate relationships

Pinealectomy Aggravates and Melatonin Administration Attenuates Brain Damage in Focal Ischemia

Large infarcts develop in pinealectomized rats subjected to middle cerebral artery occlusion, which was attributed to loss of antioxidant action of melatonin. However, melatonin also has vascular actions, and pinealectomy may induce hypertension. The authors investigated (1) whether hemodynamic factors contribute to infarct development in pinealectomized rats, (2) whether melatonin administration can reverse the unfavorable effect of pinealectomy on infarct formation, and (3) whether melatonin can reduce the infarct volume in nonpinealectomized rats subjected to focal transient ischemia (2 hours middle cerebral artery occlusion, 22 hours reperfusion). Rats were pinealectomized 3 months before ischemia to eliminate any possible action of pinealectomy-induced hypertension on stroke. Blood pressure and regional CBF values during ischemia and reperfusion were not significantly different between pinealectomized and sham-operated rats, suggesting that pinealectomy-induced increase in infarct was not related to hemodynamic factors. The infarct volume resumed to the level of sham-operated rats on melatonin administration. Injection of melatonin (4 mg/kg) before both ischemia and reperfusion reduced infarct volume by 40% and significantly improved neurologic deficit scores in pinealectomized as well as sham-operated rats subjected to middle cerebral artery occlusion. These data suggest that physiologic melatonin release as well as exogenously given melatonin has a neuroprotective action in focal cerebral ischemia

Effects of Different Weight Loss Protocols on Serum Leptin Levels in Obese Females

Summary We investigated the effects of different weight loss protocols on leptin levels in obese females with the aim of addressing the leptin resistance which has been found to be an aggravating factor in obesity. Twenty-four obese females enrolled to one of three 12-week weight loss protocols: orlistat-induced weight loss (OWL, n=8), exercise-induced weight loss (EWL, n=8) and orlistat plus exercise-induced weight loss (OEWL, n=8). Serum leptin levels were measured in duplicate by radioimmunoassay. There were significant reductions (P<0.01) in body weight and fat mass after the 12 week period in all groups: -11.4±0.5 kg and -9.8±0.5 kg (OEWL), -8.3±0.8 kg and -5.7±0.9 kg (OWL), -8.9±1.2 kg and -7.4±1.2 kg (EWL), respectively. Serum leptin levels were also decreased markedly in all groups: -59.2 % (OEWL1), -37.8 % (OWL) and -48.6 % (EWL) (P<0.01 all). In addition, there were marked decreases in leptin levels for each kilogram of fat mass after the 12 week period: -48.2±7.2 % (OEWL), -27.8±4.8 % (OWL) and -39.3±4.3 % (EWL) (P<0.01 all). Decreases in serum leptin levels expressed per kilogram of fat mass were significantly higher in the OEWL group compared to the OWL group (P=0.03). Consequently, an exercise training program in adjunct to pharmacotherapy provides higher weight reduction and fat mass loss in obesity treatment. It also seems to have further beneficial effects on leptin resistance, as indicated by decreases in leptin levels expressed per kilogram of fat mass

Posterior pituitary function in Sheehan's syndrome

Objective: We studied posterior pituitary function in 27 patients with Sheehan's syndrome and 14 controls. Design: All patients were investigated by water deprivation test and 26 of them by 5% hypertonic saline infusion test. None of the patients had symptoms of diabetes insipidus and all patients were on adequate glucocorticoid and thyroid hormone replacement therapy before testing. Results: According to dehydration test, 8 (29.6%) patients had partial diabetes insipidus (PDI group) and 19 (70.3%) had normal response (non-DI group). During the 5% hypertonic saline infusion test, the maximal plasma osmolality was higher in PDI (305±4.3) and non-DI (308±1.7) groups when compared with controls (298±1.7 mOsm/kg; P < 0.005), but the maximal urine osmolality was lower in PDI group (565±37) than in non-DI (708±45) and control (683±17 mOsm/kg) groups (P<0.05). The osmotic threshold for thirst perception was higher in PDI (296±4.3) and non-DI (298±1.4) groups when compared with control group (287±1.5 mOsm/kg) (P<0.005). Basal plasma osmolalities were also higher in PDI (294±1.0) and non-DI (297±1.1) groups than in controls (288±1.2 mOsm/kg; P<0.001). Conclusions: Our findings demonstrated that patients with Sheehan's syndrome have an impairment of neurohypophyseal function. The thirst center may be affected by ischemic damage and the osmotic threshold for the onset of thirst in patients with Sheehan's syndrome is increased. © 2007 Society of the European Journal of Endocrinology

Prevalence of polycystic ovarian changes and polycystic ovary syndrome in premenopausal women with treated type 2 diabetes mellitus

Objecti{dotless}ve: To investigate the prevalence of polycystic ovary syndrome (PCOS) and polycystic ovary (PCO) among premenopausal women with type 2 diabetes mellitus (DM). Desi{dotless}gn: Case-control study of women with type 2 DM. Setti{dotless}ng: Tertiary referral university hospital. Pati{dotless}ent(s): Ninety-two premenopausal women with DM, ?30 years of age, and 20 age- and body mass index-matched healthy premenapousal eumenorrheic women were recruited into the study. Interventi{dotless}on(s): An oral glucose tolerance test was performed according to the American Diabetes Association criteria for each healthy woman. After an overnight fasting, blood samples were obtained for the determination of fasting blood glucose, LH, FSH, free T, androstenedione (A4), 17-hydroxyprogesterone (17-OHP), DHEAS, PRL, free T4, TSH, E2, and sex hormone-binding globulin (SHBG) levels. A GnRH analog (buserelin) test was carried out in 36 patients with DM and PCO (including PCOS subjects), 20 patients with DM without PCO or PCOS, and 20 healthy subjects. Mai{dotless}n Outcome Measure(s): The prevalence of PCO and PCOS in women with type 2 DM. Result(s): Fifty-seven (62%) of diabetic patients had normal ovaries, 31 (33.7%) had PCO, and 4 (4.3%) had PCOS. The women with DM (n = 92) and healthy women (n = 20) had similar basal A4, FSH, E2, 17-OHP, free T, and DHEAS levels. The LH and SHBG levels were lower and the hirsutism score higher in diabetic patients than in healthy women (P&lt;.05). Peak and area under the curve LH and FSH levels after buserelin testing were significantly higher in healthy women than in the patients (P&lt;.05). Peak A4 levels after buserelin were significantly higher in the patients than in the healthy women (P&lt;.05). Ovarian volume was significantly greater in the patients with PCO (10.1 ± 0.7 mL) than in the healthy women (7.0 ± 0.9 mL) (P&lt;.05). Conclusion(s): We conclude that PCO but not PCOS is a common finding in premenopausal women with type 2 DM. Suppression of gonadotropins, particularly LH secretion, may play a role in the absence of increased PCOS prevalence among type 2 diabetic patients. © 2006 American Society for Reproductive Medicine

Effects of estradiol benzoate on the ultrastructure of the pinealocyte in the ovariectomized rat

Objective: The aim of this study was to examine the effects of ovariectomy and ovariectomy followed by estradiol benzoate administration on the ultrastructure of pinealocytes in female rat. Design: For this purpose 15 female Wistar rats were used. Animals were divided into three groups. Group I and II were designated as sham-ovariectomized (control) and ovariectomized, respectively. Group III was ovariectomized and daily injected with estradiol benzoate for one month. At the end of the experiment, all animals were anesthetized with ketamine for fixation by vascular perfusion. Pineal glands of groups I, II and III were removed. All specimens were examined by electron microscopy. Results: Ovariectomy caused an increase of lipid droplets, mitochondria and ribosomes. Rough endoplasmic reticulum was extensive in the cytoplasm. Estradiol administration to ovariectomized rats resulted in formation of less extensive lipid droplets, mitochondria and ribosomes compared to pinealocyte ultrastructure of both control and ovariectomized rats. Extensiveness of rough endoplasmic reticulum in the pinealocytes of estradiol-administrated rats was similar to that in controls. Conclusions: The results confirm relationship between the pineal gland and gonads in the rat and it has been suggested that estradiol benzoate reverses the ultrastructural changes, which indicate increased cell activation, occurring in the pinealocytes after ovariectomy

Investigation of adrenal functions in patients with idiopathic hyperandrogenemia

Objective: Some patients with hyperandrogenemia had no identifiable cause, which was named as idiopathic hyperandrogenemia (IHA). The role of the adrenal glands in these patients was investigated. Design: Clinical study in patients with IHA at the Endocrinology Department of a University Hospital. Patient(s): In this study, 26 pre-menopausal women with IHA and 20 healthy women were included. Basal hormonal investigations, ACTH test and a 75 g oral glucose tolerance test (OGTT) were performed. Basal levels of total testosterone, free testosterone, androstenedione (A4), sex hormone-binding globulin, DHEA sulfate (DHEAS), cortisol, 17-hydroxyprogesterone (17-OHP), 11-deoxycortisol (11-S) and ACTH-stimulated levels of cortisol, A4, DHEAS, 17-OHP, and 11-S were measured. Additionally, glucose and insulin responses to OGTT were obtained. Results: The patients and the control subjects had similar age and body mass index. Peak and area under the curve (AUC) responses of 11-S (P &lt; 0.05), DHEAS (P &lt; 0.005), and A4 (peak, P &lt; 0.005; AUC, P &lt; 0.00 1) to ACTH test were significantly higher in the patients with IHA than in the control subjects. There was a significant correlation between the basal DHEAS levels, peak 11-S, and AUC,11-s, in response to ACTH-stimulation test in patients with IHA (P &lt; 0.005, r, 0.6). Four (16.6%) patients with IHA had glucose intolerance. Conclusion: Our data suggest that adrenal androgen excess may play an important role in patients with IHA and these patients exhibit increased prevalence of glucose intolerance. © 2006 Society of the European Journal of Endocrinology