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.     

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.     

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。