Changes In Endocrine Function Research Articles

Exposure to emissions generated by 3-dimensional printing with polycarbonate: effects on peripheral vascular function, cardiac vascular morphology and expression of markers of oxidative stress in male rat cardiac tissue

ABSTRACT Three-dimensional (3D) printing with polycarbonate (PC) plastic occurs in manufacturing settings, homes, and schools. Emissions generated during printing with PC stock and bisphenol-A (BPA), an endocrine disrupter in PC, may induce adverse health effects. Inhalation of 3D printer emissions, and changes in endocrine function may lead to cardiovascular dysfunction. The goal of this study was to determine whether there were any changes in markers of peripheral or cardiovascular dysfunction in animals exposed to PC-emissions. Male Sprague Dawley rats were exposed to PC-emissions generated by 3D printing for 1, 4, 8, 15 or 30 d. Exposure induced a reduction in the expression of the antioxidant catalase (Cat) and endothelial nitric oxide synthase (eNos). Endothelin and hypoxia-induced factor 1α transcripts increased after 30 d. Alterations in transcription were associated with elevations in immunostaining for estrogen and androgen receptors, nitrotyrosine, and vascular endothelial growth factor in cardiac arteries of PC-emission exposed animals. There was also a reduction eNOS immunostaining in cardiac arteries from rats exposed to PC-emissions. Histological analyses of heart sections revealed that exposure to PC-emissions resulted in vasoconstriction of cardiac arteries and thickening of the vascular smooth muscle wall, suggesting there was a prolonged vasoconstriction. These findings are consistent with studies showing that inhalation 3D-printer emissions affect cardiovascular function. Although BPA levels in animals were relatively low, exposure-induced changes in immunostaining for estrogen and androgen receptors in cardiac arteries suggest that changes in the action of steroid hormones may have contributed to the alterations in morphology and markers of cardiac function.

Metyrosine-associated endocrinological changes in pheochromocytoma and paraganglioma.

Metyrosine (alpha-methyl-para-tyrosine) effectively reduces catecholamine levels in patients with pheochromocytoma/paraganglioma. However, improvements in physiological and metabolic parameters and changes in endocrine function associated with metyrosine administration should be validated in comparison to surgery. This study was performed to confirm the effects of metyrosine on the physiological, metabolic, and endocrinological functions of patients with pheochromocytoma/paraganglioma in the perioperative period. This retrospective cohort study was performed at a single university hospital. We included ten patients with pheochromocytoma/paraganglioma who received oral metyrosine after α-blocker therapy and consecutive surgeries. Urinary catecholamine metabolite levels and other clinical parameters were evaluated before and after metyrosine administration, and 1 week after surgery. The mean age was 53.1 ± 16.1 years. Of the ten participants (four men and six women), nine had pheochromocytoma and one had paraganglioma. The median maximum metyrosine dose was 750 mg/day. Urinary catecholamine metabolite levels significantly decreased in a dose-dependent manner after metyrosine administration. Both systolic and diastolic blood pressure significantly decreased after metyrosine and surgical treatment. Metyrosine administration significantly improved insulin sensitivity, although surgery improved the the basal insulin secretion. Additionally, serum prolactin and thyroid-stimulatory hormone levels were significantly increased by metyrosine treatment, whereas plasma renin activity was decreased. Metyrosine significantly reduced catecholamines in patients with pheochromocytoma/paraganglioma and ensured the safety of the surgery. Adjustment of metyrosine administration may make surgical pretreatment more effective in achieving stabilized blood pressure and improving glucose metabolism. Endocrine parameters may manifest as the systemic effects of metyrosine administration.

Single Cell Analysis of Human Thyroid Reveals the Transcriptional Signatures of Aging.

The thyroid gland plays a critical role in the maintenance of whole-body metabolism. However, aging frequently impairs homeostatic maintenance by thyroid hormones due to increased prevalence of subclinical hypothyroidism associated with mitochondrial dysfunction, inflammation, and fibrosis. To understand the specific aging-related changes of endocrine function in thyroid epithelial cells, we performed single-cell RNA sequencing (RNA-seq) of 54 726 cells derived from pathologically normal thyroid tissues from 7 patients who underwent thyroidectomy. Thyroid endocrine epithelial cells were clustered into 5 distinct subpopulations, and a subset of cells was found to be particularly vulnerable with aging, showing functional deterioration associated with the expression of metallothionein (MT) and major histocompatibility complex class II genes. We further validated that increased expression of MT family genes are highly correlated with thyroid gland aging in bulk RNAseq datasets. This study provides evidence that aging induces specific transcriptomic changes across multiple cell populations in the human thyroid gland.

Effects of training on plasmatic cortisol and testosterone in football female referees.

There is very little about the impact that sports training has on female football referees. Therefore, we determined the effects of a 40‐week physical preparation, including a full football season, on plasma testosterone and cortisol concentrations and physical performance in female football referees. Plasma cortisol and testosterone concentrations were assayed together with fitness tests at the beginning of the training period (T0, in September), after 8 weeks from T0 (T1), at the mid of the season (T2, 24 weeks after T0), and at the end of the season (T3, in June, 40 weeks after T0). Plasma cortisol increased during the first period and up to T2 (from 15.4 ± 4.7 to 28.5 ± 3.9 µg/dl; p < 0.001), and then decreased at the end of the season (T3: 16.0 ± 2.4 µg/dl). Plasma testosterone concentration in T0 was 14.2±0.37 µg/dl and increased in T1 (57.1 ± 3.7 µg/dl) and T2 (47 ± 3.7 µg/dl) and then decreased in T3 (33.5 ± 2.8 µg/dl). Resting testosterone levels in women were very low (14,2 ± 0.37 µg/dl) (Figure 3c). Testosterone increased in T1 (57.1 ± 3.7 µg/dl) and T2 (47 ± 3.7 µg/dl) whilst, at the end of the season, its concentration decreased (33.5 ± 2.8 µg/dl) (Figure 3c). Significant improvements were observed in all physical performances during the observed period (ANOVA, p < 0.05). Finally, testosterone and cortisol concentrations significantly (p < 0.0001 for both) correlated with maximal oxygen consumption. In T1, testosterone concentration was also significantly correlated with running speed test (p < 0.001). In conclusion, training induces endocrine changes in order to maintain body homeostasis in women referees. It is important that coaches and sports scientists regularly observe changes in endocrine function induced by training and matches in female referees, because they can help maximize referees’ performance and limit cases of overtraining.

P105 Endocrine, autonomic and vascular function in children with Sleep Disordered Breathing

Abstract SDB is a risk factor for cardiovascular disease and co-exists with chronic endocrine disorders such as type II diabetes and metabolic syndrome. Children with SDB have increased blood flow velocity, an indicator of reduced vascular compliance and early vascular aging. Increased blood flow velocity is positively associated with sympathetic activity, increased arterial sympathetic nerve fibre density and endothelial damage. Whether changes in endocrine function occur concomitantly with altered autonomic and vascular function in children with SDB was assessed. Thirty six children scheduled for tonsillectomy underwent overnight polysomnography (SDB severity), pupil light reflex (autonomic function), fasting brachial artery blood flow assessment (vascular function - Doppler Ultrasound). Leptin and Ghrelin - both hormonal markers associated with sympathetic activity were measured in urine using ELISA and serum using MagPlex. The following dimensions of the dorsal lingual artery (tonsil) were measured – medial thickness, medial area, smooth muscle cell number/layers. We observed a positive correlation between serum and urine leptin and ghrelin concentrations. Increased blood flow velocity and arterial medial thickness were both associated with increased serum and urine leptin and ghrelin concentrations. Pupil light reflex was negatively associated with serum leptin and ghrelin levels. OAHI was positively correlated with leptin and ghrelin concentration (urine and serum) but not blood flow velocity. Blood flow velocity was inversely correlated with SpO2 nadir (REM). Our findings suggest that SDB has a global effect on the autonomic, vascular and endocrine systems.The impact of untreated paediatric SDB on the development of comorbidities in later life needs urgent attention.

Changes in serum testosterone and anti-Müllerian hormone concentration in bulls undergoing scrotal insulation

While changes in semen quality after heat stress are well characterized in the bull, changes in endocrine function have not been critically evaluated. It was hypothesized here that scrotal insulation results in alterations in Sertoli cell and Leydig cell function, as measured by changes in serum testosterone and anti-Müllerian hormone (AMH) concentration. Scrotal insulation bags were placed in 10 bulls for 8 d. Blood was collected on days -22 and -2, and weekly from days 5 to 96 (day 0 = first day of scrotal insulation) for measurement of serum concentration of AMH and testosterone using ELISA. The concentration of AMH decreased on day 5, followed by an increase on day 54 (P = 0.014). When AMH concentration was normalized to pre-insulation values, the percent increase in serum concentration of AMH was significant between days 26 and 54, with another peak at 75 d (P = 0.031). The serum concentration of testosterone (P = 0.0001) and the percentage of change in testosterone concentration (P < 0.0001) increased on day 5, followed by a decrease from days 33 to 96. Scrotal insulation was associated with Sertoli and Leydig cell dysfunction, as measured by serum testosterone and AMH concentration. The persistently low concentration of testosterone at the end of the study suggests a long term effect of scrotal insulation on Leydig cell function.

The association of sarcopenia and osteoporosis and their role in falls and fractures (literature review)

The progressive and generalized loss of skeletal muscle mass and strength leads to sarcopenia in elderly people. A new geriatric syndrome has been revealed – osteosarcopenia (osteosarcoporosis), which combines low bone mineral density with reduced muscle mass, strength and functional activity. The review presents data on the peculiarities of manifestation of these syndromes, the mechanisms of which are multifactorial and continue to be investigated. They are associated with genetic factors, lifestyle – lack of physical activity and malnutrition. The pathogenesis of sarcopenia involves mechanisms of chronic inflammation, changes in endocrine function, disturbance of neuromuscular connections and low reparation level. Sarcopenia correlates with low quality of life, disability, and death. The review analyzes the prevalence of sarcopenia which increases with age. However, there are conflicting results in the populations, which may be related to different clinical conditions, patient area, lifestyle and the use of different assessment criteria. The analysis of sarcopenia prevalence in men and women showed ambiguous results related to the studied population, involvement of different age groups of patients, different evaluation methods. Metabolic disorders in muscular and bone tissues were summarized on the basis of the analysis of the cross-influence of regulatory factors and metabolism products of these tissues; a close metabolic and functional association between them was shown. Fat infiltration of atrophied muscles and bone marrow is common in patients with sarcopenia and osteosarcoporosis, which affects muscle and bone tissue. Lipotoxicity and local inflammation stimulate the biosynthesis of pro-inflammatory cytokines. Literature analysis has shown controversial data on the association of sarcopenia and osteosarcopenia with falls and fractures, but based on meta-analysis data, which include an extensive body of information, it should be noted that individuals with sarcopenia and osteosarcopenia are more at risk of falls and fractures and require special special attention. The most common fracture in osteosarcopenia is the hip fracture.

Role of pituitary stalk and gland radiological status on endocrine function and outcome after endoscopic transsphenoidal surgery for non-functioning pituitary adenomas.

To investigate endocrine function changes after non-functioning pituitary adenomas (NFPA) transsphenoidal surgery and to search for predictors of hypopituitarism resolution and development. We included 117 patients with NFPA who underwent endoscopic transsphenoidal surgery from 2005 to 2019 by two neurosurgeons. Twenty-one patients were excluded because of previous pituitary surgery or radiotherapy. We assessed symptoms at diagnosis, tumour volume, tumour removal, hormonal status at diagnosis, hormonal outcomes at 2- and 12-month follow-up, and complications. Pituitary stalk and gland MRI status (visible or not) were included, and it theirs association to hormonal function was studied for the first time, to our knowledge. Pituitary gland visualization was more frequent in those patients who showed a smaller number of axes affected at 12 months (p = 0.011). Pituitary stalk status showed no association to hormonal function. The hormonal normalization rate at 12 months was 13%. The endocrine improvement rate at 12 months was 16.7%. Worsening of hormonal function occurred in 19.8% of patients. Younger age was associated to hormonal improvement (p = 0.004). Higher preoperative tumour volume (p = 0.015) and absence of gross total resection (GTR) (p = 0.049) were associated with worsening in at least one hormonal axis after surgery. Pituitary gland visibility was higher in those patients who showed better hormonal outcomes. Assessment of initial hormonal function and outcome after surgery regarding pituitary stalk status showed no significant association. Higher preoperative tumour volumes and absence of GTR were associated to postoperative endocrine function worsening, while younger age was associated to its improvement.

Distinct effects of carbohydrate ingestion timing on glucose fluctuation and energy metabolism in patients with type 2 diabetes: a randomized controlled study.

This randomized, open-label, and parallel-group study aimed to investigate the effects of altering the timing of carbohydrate intake at breakfast or dinner on blood glucose fluctuations and energy metabolism. A total of 43 participants with type 2 diabetes were assigned to either the breakfast or dinner group. Participants were provided an isocaloric carbohydrate-restricted diet constituting 10% carbohydrate only at breakfast or dinner for 2 days during the study. Glucose fluctuations were compared using a continuous glucose monitoring system (iPro2) and body composition, energy expenditure, blood biochemistry, and endocrine function changes. The carbohydrate restriction either at breakfast or dinner significantly decreased postprandial glucose excursion and mean 24-h blood glucose levels. The incremental blood glucose area under the curve (AUC) for 2 h (iAUC0-2h) at lunch significantly increased in the breakfast group, whereas no significant differences were observed in the iAUC0-2h between breakfast and lunch in the dinner group. Carbohydrate restriction reduced diet-induced thermogenesis at breakfast (intragroup comparison; 223 ± 117 to 109 ± 104 kcal, p = 0.002) but did not affect diet-induced thermogenesis at dinner. However, fasting plasma free fatty acids were comparable in both groups, prelunch free fatty acids increased significantly only in the breakfast group (0.20 ± 0.09 to 0.63 ± 0.19 mEq/L, p < 0.001). Carbohydrate restriction in the diet once daily decreases mean 24-h blood glucose levels and exerts unique metabolic effects depending on the timing.

Pancreatic Regeneration and Changes in Endocrine Function after Pancreatectomy

Background: Limited evidence is available on the regeneration of and functional changes to remnant pancreas after pancreatectomy. Therefore, we investigated the correlation between changes in volume and endocrine function in the remnant pancreas. Methods: Ninety patients undergoing pancreaticoduodenectomy (PD) and 45 undergoing distal pancreatectomy (DP) from January 2009 to December 2017 were included in this prospective study. Computed tomography was used to determine the volume of remnant pancreas 3 months, 1 year, and 2 years after pancreatectomy. Findings: The remnant pancreas volume compared to the initial residual pancreas was 80·79%, 68·67%, and 65·34% in the PD patients (p<0·001), and 106·25%, 106·62%, and 110·43% (p=0·019) in the DP patients at 3 months, 1 year, and 2 years, respectively. The DP patients had a higher incidence of new-onset diabetes than PD patients (33·3% vs. 22·7%). In addition, PD patients had more pancreatic duct dilatation with severe atrophy of the remnant pancreas (p=0·027), whereas DP patients had better pancreas regeneration (p=0·084) with spleen preservation. The changes in pancreas volume did not correlate with postoperative new-onset diabetes. Interestingly, the PD group had significantly greater restoration of endocrine function based on secretion of C-peptide. Interpretation: Pancreatic regeneration is more predominant after DP than PD. The distal portion of the pancreas had greater restoration capacity, corresponding with a lower rate of new-onset diabetes. Funding Statement: The study was supported by Taiwan Ministry of Science and Technology (MOST108-2321-B-006-014), Ministry of Health and Welfare (MOHW 107-TDU-B-212-114026A), and HSU-YUAN Education Foundation (HY-2018-001). Declaration of Interests: The authors reported no conflict of interest. Ethics Approval Statement: IRB approved by the Institutional Review Board of the National Cheng Kung University Hospital (approval number of B-ER-108-312).

Blubber steroid hormone profiles as indicators of physiological state in free-ranging common bottlenose dolphins (Tursiops truncatus)

Blubber has been proposed as a possible alternative to blood in the assessment of endocrine physiology in marine mammals because it can be collected via remote biopsy, which removes some of the confounding variables and logistical constraints associated with blood collection. To date, few studies have directly assessed the relationships between circulating versus blubber steroid hormone profiles in marine mammals, and these studies have been limited to a small subset of steroid hormones, which collectively limit the current utility of blubber steroid hormone measurements. In this study, we used liquid-chromatography tandem-mass spectrometry (LC-MS/MS) to screen for 16 steroid hormones in matched blood and blubber samples from free-ranging common bottlenose dolphins (Tursiops truncatus). Seven steroid hormones were detected and quantified, including two progestogens, two androgens, and three corticosteroids. Using principal components analysis (PCA), we explored relationships between hormones in both matrices and three physiological states: sexual maturity, pregnancy, and acute stress response. Plasma and blubber testosterone and its precursors, 17-hydroxyprogesterone and androstenedione, loaded to the first principal component (PC1), and PC1 scores were higher in mature males. Plasma and blubber progesterone loaded to PC2, and pregnant/probable pregnant females had significantly higher PC2 scores. Pregnant females also had higher PC1 scores than other females, suggesting differences in androgen profiles between these groups. There was disagreement between plasma and blubber corticosteroid profiles, as indicated by their loading to different PCs; plasma corticosteroids loaded to PC3 and blubber corticosteroids to PC4. PC3 scores were significantly predicted by elapsed time to blood collection (i.e., time between initiating the capture process and blood collection), while elapsed time to blubber collection significantly predicted PC4 scores, indicating that corticosteroid profiles shift in both tissues during acute stress. Corticosteroid profiles were not related to demographic group, site-month, body mass index, water temperature, or time spent outside of the water on the processing boat. Overall, these results demonstrate that blubber steroid hormone profiles reflect changes in endocrine function that occur over broad temporal scales.

Nutritional influences on reproduction in mature male sheep and goats

Changes in the nutrition of mature rams and goat bucks lead to profound responses in testicular size and therefore the rate of production of spermatozoa. These effects are largely due to changes in the size of the seminiferous tubules and in the efficiency of spermatogenesis. With the exception of severe undernutrition, the effects on spermatogenic function are not accompanied by similar changes in endocrine function of the testes, as measured by the production of testosterone or inhibin. In rams, moderate changes in nutrition affect gonadotrophin secretion for only a few weeks, whereas testicular growth is affected for several months. In mature male goats during the non-breeding season, nutrition-induced testicular growth does not seem to be associated with a gonadotrophin response. Such observations have led us to develop the hypothesis that nutrition-driven testicular growth is at least partly independent of changes in gonadotrophin secretion. The energetic components of the diet, rather than the protein content, seem to be responsible for affecting gonadotrophin secretion in rams. The volatile fatty acids, and not glucose, are the active factors, although intracerebral insulin may also play a role. Where these substrates act and whether they are also involved in the gonadotrophin-independent pathways requires testing. In conclusion, nutritional signals exert powerful effects on the reproductive system of mature male ruminants, and the responses are partly independent of changes in gonadotrophin secretion. In the gonads, the gametogenic tissue responds rapidly to changes in nutrition, but the endocrine compartments are less affected. Variations in the expression of the nutritional responses among sexes, breeds and species probably reflect variations in the role of this environmental factor as a modulator of reproductive function.

A critical review of the environmental occurrence and potential effects in aquatic vertebrates of the potent androgen receptor agonist 17β-trenbolone.

Trenbolone acetate is widely used in some parts of the world for its desirable anabolic effects on livestock. Several metabolites of the acetate, including 17β-trenbolone, have been detected at low nanograms per liter concentrations in surface waters associated with animal feedlots. The 17β-trenbolone isomer can affect androgen receptor signaling pathways in various vertebrate species at comparatively low concentrations/doses. The present article provides a comprehensive review and synthesis of the existing literature concerning exposure to and biological effects of 17β-trenbolone, with an emphasis on potential risks to aquatic animals. In vitro studies indicate that, although 17β-trenbolone can activate several nuclear hormone receptors, its highest affinity is for the androgen receptor in all vertebrate taxa examined, including fish. Exposure of fish to nanograms per liter water concentrations of 17β-trenbolone can cause changes in endocrine function in the short term, and adverse apical effects in longer exposures during development and reproduction. Impacts on endocrine function typically are indicative of inappropriate androgen receptor signaling, such as changes in sex steroid metabolism, impacts on gonadal stage, and masculinization of females. Exposure of fish to 17β-trenbolone during sexual differentiation in early development can greatly skew sex ratios, whereas adult exposures can adversely impact fertility and fecundity. To fully assess ecosystem-level risks, additional research is warranted to address uncertainties as to the degree/breadth of environmental exposures and potential population-level effects of 17β-trenbolone in sensitive species. Environ Toxicol Chem 2018;37:2064-2078. Published 2018 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Hysterectomy and perceived physical function in middle-aged Australian women: a 20-year population-based prospective cohort study.

Hysterectomy is one of the most common gynaecological procedures worldwide. Changes in endocrine function may impact age-associated decline in physical function and these changes may be accelerated by hysterectomy. The aim of this study was to investigate associations between hysterectomy status and self-reported physical function limitations. Our study sample (n = 8624) came from the mid-cohort (born 1945-1950) of the Australian Longitudinal Study on Women's Health (ALSWH). Self-report of physical function was measured by the Physical Functioning (PF) subscale of the Medical Outcomes Study Short Form Health Survey (SF-36) over seven surveys (1998-2016), categorised into substantial, moderate and minimal PF-limitations. The associations between hysterectomy status and de novo substantial or moderate PF-limitations versus minimal PF-limitations were investigated using log-multinomial regression. By Survey 8 (2016), 20% of the study sample had a hysterectomy with ovarian conservation (hysterectomy only) and 9% had a hysterectomy and both ovaries removed (hysterectomy-bilateral oophorectomy). Women with a hysterectomy only had a small increase in risk of substantial PF-limitations (versus minimal PF-limitations) compared to women with no hysterectomy (relative risk [RR]: 1.13; 95% confidence interval [95% CI] 1.00-1.27); the point estimate was stronger for women with a hysterectomy-bilateral oophorectomy (RR: 1.26; 95% CI 1.09-1.46). In a supplementary analysis, the increased risk of substantial PF-limitations was seen only in women who had surgery before the age of 45years. Compared to women with no hysterectomy, women with hysterectomy-bilateral oophorectomy were at increased risk of substantial PF-limitations versus minimal PF-limitations over 18 years of follow-up.

The impact of pancreaticoduodenectomy on endocrine and exocrine pancreatic function: A prospective cohort study based on pre- and postoperative function tests

Background/ObjectivesStudies reporting on function after pancreatic surgery are frequently based on diabetes history, fasting glycemia or random glycemia. The aim of this study was to investigate prospectively the evolution of pancreatic function in patients undergoing pancreaticoduodenectomy based on proper pre- and postoperative function tests. It was hypothesised that pancreatic function deteriorates after pancreaticoduodenectomy. MethodsBetween 2013 and 2016, 78 patients undergoing pancreaticoduodenectomy for oncologic indications had a prospective evaluation of their endocrine and exocrine pancreatic function. Endocrine function was evaluated with the 75 g oral glucose tolerance test (OGTT) and the 1 mg intravenous glucagon test. Exocrine function was evaluated with a 13C-labelled mixed-triglyceride breath test. Tests were performed pre- and postoperatively. ResultsIn 90.5% (19/21) of patients with preoperatively known diabetes, no change in endocrine function was observed. In contrast, endocrine function improved in 68.1% (15/22) of patients with newly diagnosed diabetes. 40% (14/35) of patients with a preoperative normal OGTT or prediabetes experienced deterioration in function. In multivariate analysis, improvement of newly diagnosed diabetes was correlated with preoperative bilirubin levels (p = 0.045), while progression towards diabetes was correlated with preoperative C-peptidogenic index T30 (p = 0.037).A total of 20.5% (16/78) of patients had pancreatic exocrine insufficiency preoperatively. Another 51.3% (40/78) of patients deteriorated on exocrine level. In total, 64.1% (50/78) of patients required pancreatic enzyme-replacement therapy postoperatively. ConclusionsAlthough deterioration of endocrine function was expected after pancreatic resection, improvement is frequently observed in patients with newly diagnosed diabetes. Exocrine function deteriorates after pancreaticoduodenectomy.

Association between endocrine function and radiation exposure

Background: To observe the relationship of change in endocrine function within radiation exposure and try to evaluate the correlated factors about thyroid function and glucose metabolism. Methods: A total of 1,784 subjects from physical examination organization for occupational health from year 2015 to 2016 were investigated. Results: The abnormal proportion of T3 and T4 of female were higher than male. Glucose level showed a significant increase in overweight (5.35±1.01) and decrease in underweight group (4.77±0.47) compared with normal group (5.05±0.85). Subjects whose exposure time longer than 3 years were likely to get higher T4 level than those less than 3 years (P Conclusions: Changes in thyroid function and glucose metabolism may appear after long time exposure to radiation.

Challenges in assigning endocrine-specific modes of action: Recommendations for researchers and regulators.

As regulatory programs evaluate substances for their endocrine-disrupting properties, careful study design and data interpretation are needed to distinguish between responses that are truly endocrine specific and those that are not. This is particularly important in regulatory environments where criteria are under development to identify endocrine-disrupting properties to enable hazard-based regulation. Irrespective of these processes, most jurisdictions use the World Health Organization/International Programme on Chemical Safety definition of an endocrine disruptor, requiring that a substance is demonstrated to cause a change in endocrine function that consequently leads to an adverse effect in an intact organism. Such a definition is broad, and at its most cautious might capture many general mechanisms that would not specifically denote an endocrine disruptor. In addition, endocrine responses may be adaptive in nature, designed to maintain homeostasis rather than induce an irreversible adverse effect. The likelihood of indirect effects is increased in (eco)toxicological studies that require the use of maximum tolerated concentrations or doses, which must produce some adverse effect. The misidentification of indirect effects as truly endocrine mediated has serious consequences for prompting animal- and resource-intensive testing and regulatory consequences. To minimize the risk for misidentification, an objective and transparent weight-of-evidence procedure based on biological plausibility, essentiality, and empirical evidence of key events in an adverse outcome pathway is recommended to describe the modes of action that may be involved in toxic responses in nontarget organisms. Confounding factors such as systemic toxicity, general stress, and infection can add complexity to such an evaluation and should be considered in the weight of evidence. A recommended set of questions is proffered to help guide researchers and regulators in discerning endocrine and nonendocrine responses. Although many examples provided in this study are based on ecotoxicology, the majority of the concepts and processes are applicable to both environmental and human health assessments. Integr Environ Assess Manag 2017;13:280-292. © 2016 SETAC.

Clinicopathological features and BRAFV600E mutations in patients with isolated hypothalamic-pituitary Langerhans cell histiocytosis.

BackgroundIsolated hypothalamic-pituitary Langerhans cell histiocytosis (HPLCH) is very rare. We investigated the clinicopathological characteristics, endocrine function changes, BRAFV600E mutations and treatments of isolated HPLCH.MethodsWe identified seven patients with isolated HPLCH by reviewing the clinical and pathological files in our hospital from 2007 to 2015. The clinical characteristics of the seven patients were retrospectively reviewed, especially the endocrine function changes. Immunostaining and mutation profiling of BRAFV600E were performed.ResultsThe seven HPLCH patients included three men and four women, aged 9–47 years. All patients presented with symptoms of central diabetes insipidus (CDI), and four displayed anterior pituitary hypofunction as well. Magnetic resonance imaging showed hypothalamic-pituitary axis involvement in all patients. There was no evidence for the involvement of other organs in all seven patients. Langerhans cell histiocytosis was confirmed by neuroendoscopic procedures, and immunohistochemical staining showed that all cases (7/7) were positive for CD68, CD1a, Langerin, and S-100. The BRAFV600E mutation was detected in three of the six cases (3/6). Six patients had follow-up information; all received desmopressin acetate and high-dose corticosteroid therapy, and two patients received radiotherapy.ConclusionsOur study indicated that all patients with isolated HPLCH had CDI as the earliest symptom, and more than half of the patients had anterior pituitary deficiencies. The BRAFV600E mutation is a common genetic change in HPLCH patients. Treatment of HPLCH patients is difficult, and the progressive loss of endocrine function is irreversible in most cases.

Effect of subchronic corticosterone administration on α2-adrenoceptor functionality in rat brain: an in vivo and in vitro study.

Noradrenergic system plays a critical role in the hypothalamic-pituitary-adrenal (HPA) axis regulation and the stress response. A dysregulated HPA axis may be indicative of an increased biological vulnerability for depression. In addition, a variety of studies have focused on specific alterations of α2-adrenoceptors as a mechanism involved in the pathogenesis of mood disorders and antidepressant response. This study aimed to evaluate the effect of subchronic corticosterone administration on rat brain α2-adrenoceptor functionality by in vitro [35S]GTPγS binding stimulation assays and in vivo dual-probe microdialysis determination of extracellular noradrenaline concentrations. Implantation of a time release corticosterone pellet during 14days induced sustained changes in endocrine function. However, there were no differences in α2-adrenoceptor agonist UK14304-induced stimulation of [35S]GTPγS binding in prefrontal cortex (PFC) between corticosterone-treated and control rats. In the same way, the in vivo evaluation of α2-adrenoceptor-mediated noradrenaline release responses to the α2-adrenoceptor agonist clonidine local administration into the locus coeruleus (LC), and the PFC did not show differences between the groups. The present results show that subchronic corticosterone administration does not induce changes on functionality of α2-adrenoceptors neither in the LC nor in noradrenergic cortical terminal areas.

Hormones and the Evolution of Complex Traits: Insights from Artificial Selection on Behavior.

Although behavior may often be a fairly direct target of natural or sexual selection, it cannot evolve without changes in subordinate traits that cause or permit its expression. In principle, changes in endocrine function could be a common mechanism underlying behavioral evolution because they are well positioned to mediate integrated responses to behavioral selection. More specifically, hormones can influence both motivational (e.g., brain) and performance (e.g., muscles) components of behavior simultaneously and in a coordinated fashion. If the endocrine system is often "used" as a general mechanism to effect responses to selection, then correlated responses in other aspects of behavior, life history, and organismal performance (e.g., locomotor abilities) should commonly occur because any cell with appropriate receptors could be affected. Ways in which behavior coadapts with other aspects of the phenotype can be studied directly through artificial selection and experimental evolution. Several studies have targeted rodent behavior for selective breeding and reported changes in other aspects of behavior, life history, and lower-level effectors of these organismal traits, including endocrine function. One example involves selection for high levels of voluntary wheel running, one aspect of physical activity, in four replicate High Runner (HR) lines of mice. Circulating levels of several hormones (including insulin, testosterone, thyroxine, triiodothyronine) have been characterized, three of which-corticosterone, leptin, and adiponectin-differ between HR and control lines, depending on sex, age, and generation. Potential changes in circulating levels of other behaviorally and metabolically relevant hormones, as well as in other components of the endocrine system (e.g., receptors), have yet to be examined. Overall, results to date identify promising avenues for further studies on the endocrine basis of activity levels.