Ontogeny of the hypothalamo-pituitary-adrenocortical axis in the chicken embryo: a review

The embryo of the domestic fowl (Gallus domesticus) tenders one distinctive advantage over general mammalian models for investigating the development of the hypothalamo–pituitary–adrenocortical (HPA) axis. This is the relative simplicity with which the embryonic endocrine environment can be influenced without confounding maternal influences. The ease of direct manipulation of the embryonic endocrine system has facilitated analysis of the development and function of the HPA axis in the chick embryo. As the chick embryo develops, functional activation of the adrenal gland is regulated at three different levels: the adrenal gland itself, the anterior pituitary, and the hypothalamus. The adrenal gland appears capable of independent secretion of glucocorticoids from day 8 until shortly after day 14 of embryonic development, at which point the pituitary influences adrenocortical activity. Around the same age, the hypothalamic level of control also begins. The information covered in this review will describe the major steps in the development of the HPA axis in the chicken embryo and show that the chicken has an emblematic HPA neuroendocrine axis.     

Stress in a conservation context: A discussion of glucocorticoid actions and how levels change with conservation-relevant variables

Over the past few decades, there has been a steep increase in the number of conservation-related field studies that measure glucocorticoid hormones (corticosterone or cortisol) as a marker for stress. Endocrine tools show great potential for informing conservation, however interpretation of results is often complicated. This paper reviews the role of glucocorticoids for non-physiologists, evaluates select applications of glucocorticoid measures to conservation field studies, and proposes a theoretical model to focus future research. Because levels of glucocorticoids typically increase in response to challenge and sometimes predict mortality or decrease reproduction, it is often assumed that high levels of glucocorticoids indicate stress. However, literature review suggests that glucocorticoid measures fail to change consistently in a predictable manner with adverse conditions and do not always show a linear correlation with survival or reproductive success. Inconsistencies relate in part to methodological problems but also have a physiological basis. We propose that relationships between (1) glucocorticoids and fitness and (2) glucocorticoids and disturbance may be more log quadratic rather than linear. We hope these models will be useful in generating predictions for future studies and resolving the inconsistencies that currently complicate interpretation for conservation endocrinologists.     

A novel NF-κB inhibitor improves glucocorticoid sensitivity of canine neoplastic lymphoid cells by up-regulating expression of glucocorticoid receptors

Lymphoid neoplasms including lymphoma and leukemia are one of the most life-threatening disorders in dogs. Many lymphoid malignancies are well-treated with glucocorticoid (GC); however, GC resistance sometimes develops and its mechanism remains uncertain. Since constitutive activation of nuclear factor-κB (NF-κB) has been reported to play roles in lymphoid malignancies, we examined whether inhibition of NF-κB activity with a synthetic inhibitor IMD-0354 affected GC sensitivity of canine neoplastic lymphoid cells, CL-1 and GL-1. Dexamethasone failed to inhibit proliferation of these cells, in which low expression of glucocorticoid receptors (GR) was identified. In the presence of IMD-0354, GR expressions in CL-1 and GL-1 were increased, consequently dexamethasone inhibited their proliferation. These results indicated that GR expression might be down-regulated by spontaneous activation of NF-κB, resulting in GC resistance. Taken together, interference of NF-κB activity may have the synergistic effect in combination chemotherapy with GC for treatment against lymphoid malignancies.     

Long non-coding RNA HOTAIR modulates proliferation and apoptosis of acute lymphoblastic leukemia cells

AIM: To explore the influence of long non-coding RNA HOTAIR on the proliferation and apoptosis of acute lymphoblastic leukemia cells via the regulation of glucocorticoid receptor (GR).METHODS: The expression le-vels of HOTAIR and GR mRNA in human bone marrow stromal cell line HS-5 and human acute lymphoblastic leukemia cell lines MOLT-4, CCRF-CEM and CEM-C1 were examined by RT-qPCR. HOTAIR was knocked down by siRNA in acute lymphoblastic leukemia cells. CCK-8 assay was used to assess the cell viability, and the effect of si-HOTAIR on the proli-feration of CEM-C1 cells was evaluated by BrdU method. The effect of si-HOTAIR on apoptosis of CEM-C1 cells was examined by Hoechst 33342 staining and Caspase-Glo^® 3/7 assay. Western blot was utilized to examine the protein level of GR.RESULTS: The expression level of HOTAIR in acute lymphoblastic leukemia cells was significantly increased as compared with normal human bone marrow stromal cells (P<0.01). The viability and proliferation of acute lymphoblastic cells was inhibited, the apoptosis was induced, and the anti-proliferation effect of dexamethasone on CEM-C1 cells was enhanced after knockdown of HOTAIR expression (P<0.01). The expression of GR was up-regulated at both mRNA and protein levels (P<0.01).CONCLUSION: Long non-coding RNA HOTAIR may modulate the viability, proliferation and apoptosis of acute lymphoblastic leukemia cells via a GR regulatory way.     

液相色谱-串联质谱法测定动物尿液中糖皮质激素类药物的测定

建立了动物尿液样品中泼尼松（Prednisone）、泼尼松龙（Prednisolone）、甲基泼尼松龙（Methylprednisone）、地塞米松（Demxamethasone）、倍他米松（Betamethasone）、倍氯米松（Beclometasone）、醋酸氟氢可的松（Fludrocortisone Acetate）、醋酸可的松（Cortisone Acetate）、氢化可的松（Hydrocortisone）等9种糖皮质激素类药物的测定方法,明确规定了适用范围、确定了取样量、酶解、提取净化等方法以及液相色谱条件、串联质谱条件等。该方法具有较好的灵敏度、准确度和精密度。     

A novel NF-κB inhibitor improves glucocorticoid sensitivity of canine neoplastic lymphoid cells by up-regulating expression of glucocorticoid receptors

Lymphoid neoplasms including lymphoma and leukemia are one of the most life-threatening disorders in dogs. Many lymphoid malignancies are well-treated with glucocorticoid (GC); however, GC resistance sometimes develops and its mechanism remains uncertain. Since constitutive activation of nuclear factor-κB (NF-κB) has been reported to play roles in lymphoid malignancies, we examined whether inhibition of NF-κB activity with a synthetic inhibitor IMD-0354 affected GC sensitivity of canine neoplastic lymphoid cells, CL-1 and GL-1. Dexamethasone failed to inhibit proliferation of these cells, in which low expression of glucocorticoid receptors (GR) was identified. In the presence of IMD-0354, GR expressions in CL-1 and GL-1 were increased, consequently dexamethasone inhibited their proliferation. These results indicated that GR expression might be down-regulated by spontaneous activation of NF-κB, resulting in GC resistance. Taken together, interference of NF-κB activity may have the synergistic effect in combination chemotherapy with GC for treatment against lymphoid malignancies.     

应激状态下鱼类糖皮质激素代谢及作用机理的研究进展

糖皮质激素(Glucocordicoids,GC)是由肾上腺皮质分泌的一类甾体激素,在环境胁迫条件下,血浆糖皮质激素水平会发生变化,对机体生理、免疫产生不同程度影响。但应激状态下糖皮质激素水平能否作为应激的灵敏指标还存在争议,综述了鱼类在应激状态下,影响血浆糖皮质激素浓度的因素及糖皮质激素的作用机理。     

Abnormalities of serum electrolyte concentrations in dogs with hypoadrenocorticism

BACKGROUND: The sensitivity and specificity of the sodium to potassium ratio (Na:K ratio) as a cutoff for recommendation of an adrenocorticotropic hormone (ACTH) stimulation test in dogs suspected of having hypoadrenocorticism (HA) is unknown. Additionally, abnormalities in plasma ionized calcium (iCa2+) and ionized magnesium (iMg2+) concentrations and venous pH of dogs with HA are incompletely documented. OBJECTIVES: To define the sensitivity and specificity of the Na:K ratio as a diagnostic aid for HA in dogs and to examine for associations between venous pH and the Na:K ratio, iCa2+ concentration, or iMg2+ concentration in dogs with HA. ANIMALS: Seventy-six dogs with HA and 200 dogs randomly selected from the general hospital population. METHODS: Retrospective study. Dogs were included in the study if results of an ACTH stimulation test confirmed a diagnosis of HA, the dog had a serum sodium concentration below the reference range or a serum potassium concentration above the reference range, and the dog was treated with mineralocorticoids. Receiver operating curve analysis was used to determine optimal cutoffs of sensitivity and specificity for the Na:K ratio in diagnosing HA. RESULTS: Use of Na:K ratios of 27 or 28 classified 95% of dogs correctly as diseased or not diseased. The sensitivity of a Na:K ratio of 28 was 93% (CI, 85-98%) and that of 27 was 89% (CI, 80-95%). The specificity of a Na:K ratio of 28 was 96% (CI, 92-98%) and that of 27 was 97% (CI, 93- 99%). The sensitivity and specificity of a Na:K ratio of 24 were 79% (95% CI, 67-86%) and 100% (98%, CI, 97%-100%), respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Na:K ratios of 27 or 28 identify the highest percentage of dogs with suspected mineralocorticoid and glucocorticoid deficiency correctly. In dogs with a Na:K ratio of 24 or less, the likelihood of confirming a diagnosis of HA with an ACTH stimulation test is high.