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In addition to the hypophysiotropic thyrotropin‐releasing hormone (TRH)‐synthesizing neurons, a glial cell type, the tanycytes, also play a role in the regulation of the hypothalamic‐pituitary‐thyroid (HPT) axis. Tanycytes modulate the feedback regulation of the axis by regulating the local thyroid hormone availability in the median eminence where the hypophysiotropic axons terminate. Recently, we showed that tanycytes produce diacylglycerol lipase alpha (DAGLα), the synthesizing enzyme of the endocannabinoid 2‐arachidonoylglycerol (2‐AG) that inhibits the release of TRH from the hypophysiotropic terminals in median eminence explants. To determine the importance of the endocannabinoid production of tanycytes, adult male Rax‐CreERT2//DAGLαfl/fl mice were treated with tamoxifen to induce a tanycyte specific decrease of DAGLα expression (T‐DAGLα KO). The effect of this genetic manipulation on the activity of the HPT axis was determined. Tanycyte specific decrease of DAGLα expression resulted in an approximately 2‐fold increase of TSHβ mRNA level that was accompanied by increased levels of circulating free T4. The TRH mRNA level was, however, not influenced by the genetic manipulation. In addition to the effects on the HPT axis, the T‐DAGLα KO mice showed increased fat mass ratio and decreased blood glucose levels. These data indicate that when endocannabinoid release of tanycytes is decreased, the disinhibition of the TRH release induces increased TSH synthesis and higher circulating T4 levels. Thus it suggests that in wild‐type mice, tanycytes exert a tonic inhibitory effect on the TRH release of hypophysiotropic axons. Furthermore, the endocannabinoid release of tanycytes also influences glucose homeostasis and fat deposition. [ABSTRACT FROM AUTHOR]

In this study, healthy Wuchang bream (Megalobrama amblycephala) juveniles were exposed to 0, 5, 10, 20 and 30 mg/L total ammonia nitrogen for 30 days to elucidate toxic effects and mechanisms of ammonia on growth performance involved with the regulation of growth hormone/insulin‐like growth factor (GH/IGF) and hypothalamic–pituitary‐thyroid (HPT) axes. Our results showed that the increasing total ammonia nitrogen concentrations caused dose‐depend decreases in the weight gain and specific growth rate but increases in the food conversion ratio and mortality in juvenile bream, indicating growth inhibitory effects induced by ammonia. Concurrently, GH, IGF‐1 at protein and mRNA levels were significantly decreased in ammonia exposure groups (p <.05), while serum thyroid stimulating hormone, free thyroxine, free triiodothyronine levels were significantly reduced only in fish exposed to higher concentrations of 20 and 30 mg/L ammonia (p <.05), suggesting that ammonia exposure could perturb both GH/IGF‐axis and HPT‐axis functions. Furthermore, transcriptional levels of extracellular regulated protein kinases 2 (erk2), phosphatidylinositol 3‐kinase (pi3k), protein kinase B (akt), target of rapamycin (tom) and ribosomal protein S6 kinase‐polypeptide 1(s6k1) in the dorsal muscle were significantly down‐regulated in the fish exposed to ammonia (p <.05). This fact indicated that MAPK/ERK pathway and PI3K/AKT pathway should be responsible for the growth inhibition. Combining the results of spearman correlation coefficient, it should be noted that the GH/IGF axis played a more important role in regulating the growth than the HPT axis in Wuchang bream under persistent ammonia stress. [ABSTRACT FROM AUTHOR]

Negative energy balance promotes physiological adaptations that ensure the survival of animals. The hypothalamic-pituitary-thyroid axis regulates basal energy expenditure and its down-regulating adaptation to negative energy balance is well described: in fasting, the serum content of thyrotrophin (TSH) and thyroid hormones (TH) decreases, enhancing the survival odds of individuals. By contrast, dehydration-induced anorexic (DIA) rats present an impaired hypothalamic-pituitary-thyroid (HPT) axis adaptation despite their negative energy balance: increased circulating TSH levels. The implication of cocaine- and amphetamine-regulated transcript (CART), an anorexic peptide, in HPT axis function impairment and food-avoidance behaviour displayed by DIA animals is unknown. Because CART is co-expressed with the peptide that regulates the HPT axis in hypophysiotrophic paraventricular nucleus (PVN) neurones (TSH-releasing hormone), we analysed CART expression and possible implications with respect to high TSH levels of DIA animals. We examined whether changes in CART expression from the lateral hypothalamic area (LHA) and arcuate nucleus (ARC) could participate in food-avoidance of DIA rats. DIA and forced-food restricted (FFR) animals reduced their body weight and food intake. FFR rats had a down-regulation of their HPT axis (reduced serum TH and TSH content), whereas DIA animals had reduced TH but increased TSH levels. CART mRNA expression in the ARC decreased similarly between experimental groups and diminished in anterior, medial PVN and in LHA of FFR animals, whereas DIA animals showed unchanged levels. This impaired CART mRNA expression in the anterior PVN and LHA could be related to the aberrant feeding behaviour of DIA rats but not to their deregulated HPT axis function. [ABSTRACT FROM AUTHOR]

Enantioselectivity of chiral pesticides in environmental safety has attracted more and more attention. In this study, we evaluated the enantioselective toxicity of rac-metalaxyl and R-metalaxyl to zebrafish ( Danio rerio) embryos through various malformations including pericardial edema, yolk sac edema, crooked body, and short tails. The results showed that there were significant differences in toxicity to zebrafish embryos caused by rac-metalaxyl and R-metalaxyl, and the LC50s at 96 h are 416.41 (353.91, 499.29) mg · L-1 and 320.650 (279.80, 363.46) mg · L-1, respectively. In order to explore the possible mechanism of the development defects, the genes involved in the hypothalamic-pituitary-gonadal axis ( vtg1, vtg2, cyp17, cyp19a, cyp19b) and hypothalamic-pituitary-thyroid axis ( dio1, dio2, nis, tg, tpo) were quantified by quantitative real-time polymerase chain reaction (qRT-PCR). The results revealed that there were no significant differences in the expression of vtg1, vtg2, cyp17, cyp19a, and cyp19b after exposure to rac-metalaxyl. However, the expression of vtg1, cyp19a, and cyp19b decreased significantly after exposure to R-metalaxyl. And likewise, rac-metalaxyl only caused the upregulation of dio2, while R-metalaxyl suppressed the expression of dio1 and tpo and induced the expression of dio2 and nis. The change of gene expression may cause the enantioselectivity in developmental toxicity in zebrafish embryo. The data provided here will be helpful for us to comprehensively understand the potential ecological risks of the currently used chiral fungicides. Chirality 28:489-494, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Hypothyroidism is associated with a disturbance of behaviour and mood. There are also individuals, not classified as hypothyroid, with low to ‘low normal’ thyroid hormone levels and normal thyroid-stimulating hormone (TSH) levels who have mood and behavioural changes. As the peripheral thyroid hormones decrease, TSH is expected to increase. However, there are a number of physiological mechanisms known to suppress TSH. In the present study, we report on thyroid hormone regulation in a rat model of neuropathic pain and altered social behaviour that is usually transient, but is persistent in a sub-group of the population. Following ligation of the sciatic nerve, male Sprague-Dawley rats were assessed for social dominance towards an intruder: 20% showed persistently decreased social dominance. Plasma levels of thyroid hormones, TSH and corticosterone were measured before and on days 2, 3, 4, 5 and 6 after injury in 21 rats. The mean plasma thyroxine (T4), free thyroxine (fT4) and triiodothyronine (T3) levels decreased significantly post-injury in rats with persistently changed behaviour compared to rats with unchanged behaviour (P ≤ 0.002). There was no significant difference between groups for mean change in free triiodothyronine (fT3) or TSH. There was a correlation between decreased dominance behaviour and decrease in both T4 (r = 0.62, P = 0.009) and fT4 (r = 0.71, P = 0.001), but no correlation with TSH. In a sub-population of rats, decreased thyroid hormones did not result in the expected increased levels of TSH to restore pre-injury levels, nor did they show increased hypothalamic thyrotrophin-releasing hormone mRNA expression, indicating altered hypothalamic-pituitary-thyroid axis regulation. Because T3 availability to the brain is dependent on both circulating T3 and T4, decreased peripheral thyroid hormones may result in changed neural function, as expressed in altered complex behaviours in this sub-population of rats. [ABSTRACT FROM AUTHOR]

Studies of the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-testicular (HPT) axis have revealed a reciprocal relationship between these two endocrine pathways. In rats, for example, disruption of the HPT axis alters the circadian secretion of corticosterone. Stress, on the other hand, can have varying effects on testosterone secretion in both rats and humans. Furthermore, in contrast to humans, where several pulses of testosterone secretion can be detected across the 24-h period with the largest in the morning, rats appear to exhibit a diurnal rhythm of testosterone secretion. In the present study, we used an automated blood sampling system to investigate the true circadian pattern of testosterone secretion under basal conditions and investigated how this responds to changes in levels of circulating corticosteroids. Analysis of plasma testosterone revealed the expected bimodal pattern of basal testosterone secretion. The two secretory episodes were 12.59 h ± 41 min apart and 4.04 h ± 16 min long, with one in the light phase and the other in the dark phase of the cycle. Interestingly, when both testosterone and corticosterone diurnal profile were compared, we found that the circadian rise in plasma corticosterone levels falls neatly between the two testosterone secretory episodes. Treatment of rats with the synthetic glucocorticoid methylprednisolone in their drinking water abolished the normal bimodal profile of testosterone secretion. These rats show transient pulses of testosterone throughout the 24 h, but no circadian pattern. By contrast, adrenalectomised rats maintain their bimodal circadian pattern, suggesting that an intact HPA axis is not necessary for generation of the endogenous HPT rhythm. Thus, although the circadian rhythm of testosterone does not depend on normal HPA function, increased levels of glucocorticoids can abolish normal HPT rhythmicity. [ABSTRACT FROM AUTHOR]