scholarly journals The ERβ Ligand 5α-androstane, 3β,17β-diol (3β-diol) Regulates Hypothalamic Oxytocin (Oxt) Gene Expression

Endocrinology ◽  
2012 ◽  
Vol 153 (5) ◽  
pp. 2353-2361 ◽  
Author(s):  
Dharmendra Sharma ◽  
Robert J. Handa ◽  
Rosalie M. Uht
Keyword(s):  
Gene Expression ◽  
Stress Response ◽  
Hpa Axis ◽  
Steroid Receptor ◽  
Camp Response Element Binding ◽  
Mrna Levels ◽  
Camp Response Element ◽  
Response Element ◽  
Steroid Receptor Coactivator ◽  
Element Binding Protein

The endocrine component of the stress response is regulated by glucocorticoids and sex steroids. Testosterone down-regulates hypothalamic-pituitary-adrenal (HPA) axis activity; however, the mechanisms by which it does so are poorly understood. A candidate testosterone target is the oxytocin gene (Oxt), given that it too inhibits HPA activity. Within the paraventricular nucleus of the hypothalamus, oxytocinergic neurons involved in regulating the stress response do not express androgen receptors but do express estrogen receptor-β (ERβ), which binds the dihydrotestosterone metabolite 3β,17β-diol (3β-diol). Testosterone regulation of the HPA axis thus appears to involve the conversion to the ERβ-selective ligand 5α-androstane, 3β-diol. To study mechanisms by which 3β-diol could regulate Oxt expression, we used a hypothalamic neuronal cell line derived from embryonic mice that expresses Oxt constitutively and compared 3β-diol with estradiol (E2) effects. E2 and 3β-diol elicited a phasic response in Oxt mRNA levels. In the presence of either ligand, Oxt mRNA levels were increased for at least 60 min and returned to baseline by 2 h. ERβ occupancy preceded an increase in Oxt mRNA levels in the presence of 3β-diol but not E2. In tandem with ERβ occupancy, 3β-diol increased occupancy of the Oxt promoter by cAMP response element-binding protein and steroid receptor coactivator-1 at 30 min. At the same time, 3β-diol led to the increased acetylation of histone H4 but not H3. Taken together, the data suggest that in the presence of 3β-diol, ERβ associates with cAMP response element-binding protein and steroid receptor coactivator-1 to form a functional complex that drives Oxt gene expression.

scholarly journals Involvement of Neuropeptide Y Y1 Receptors in the Regulation of Neuroendocrine Corticotropin-Releasing Hormone Neuronal Activity

Endocrinology ◽  
2007 ◽  
Vol 148 (8) ◽  
pp. 3666-3673 ◽  
Author(s):  
Eugene L. Dimitrov ◽  
M. Regina DeJoseph ◽  
Mark S. Brownfield ◽  
Janice H. Urban
Keyword(s):  
Neuropeptide Y ◽  
Hpa Axis ◽  
Binding Protein ◽  
Plasma Corticosterone ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Response Element ◽  
Y1 Receptor ◽  
Element Binding Protein ◽  
Y1 Receptors

The neuroendocrine parvocellular CRH neurons in the paraventricular nucleus (PVN) of the hypothalamus are the main integrators of neural inputs that initiate hypothalamic-pituitary-adrenal (HPA) axis activation. Neuropeptide Y (NPY) expression is prominent within the PVN, and previous reports indicated that NPY stimulates CRH mRNA levels. The purpose of these studies was to examine the participation of NPY receptors in HPA axis activation and determine whether neuroendocrine CRH neurons express NPY receptor immunoreactivity. Infusion of 0.5 nmol NPY into the third ventricle increased plasma corticosterone levels in conscious rats, with the peak of hormone levels occurring 30 min after injection. This increase was prevented by pretreatment with the Y1 receptor antagonist BIBP3226. Immunohistochemistry showed that CRH-immunoreactive neurons coexpressed Y1 receptor immunoreactivity (Y1r-ir) in the PVN, and a majority of these neurons (88.8%) were neuroendocrine as determined by ip injections of FluoroGold. Bilateral infusion of the Y1/Y5 agonist, [leu31pro34]NPY (110 pmol), into the PVN increased c-Fos and phosphorylated cAMP response element-binding protein expression and elevated plasma corticosterone levels. Increased expression of c-Fos and phosphorylated cAMP response element-binding protein was observed in populations of CRH/Y1r-ir cells. The current findings present a comprehensive study of NPY Y1 receptor distribution and activation with respect to CRH neurons in the PVN. The expression of NPY Y1r-ir by neuroendocrine CRH cells suggests that alterations in NPY release and subsequent activation of NPY Y1 receptors plays an important role in the regulation of the HPA.

scholarly journals Induction of Human NF-IL6β by Epidermal Growth Factor Is Mediated through the p38 Signaling Pathway and cAMP Response Element-binding Protein Activation in A431 Cells

2005 ◽  
Vol 16 (7) ◽  
pp. 3365-3376 ◽  
Author(s):  
Ju-Ming Wang ◽  
Joseph T. Tseng ◽  
Wen-Chang Chang
Keyword(s):  
Gene Expression ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Binding Activity ◽  
A431 Cells ◽  
Base Pairs ◽  
Camp Response Element ◽  
Response Element ◽  
Element Binding Protein ◽  
Epidermal Growth

The CCAAT/enhancer binding protein δ (C/EBPδ, CRP3, CELF, NF-IL6β) regulates gene expression and plays functional roles in many tissues, such as in acute phase response to inflammatory stimuli, adipocyte differentiation, and mammary epithelial cell growth control. In this study, we examined the expression of human C/EBPδ (NF-IL6β) gene by epidermal growth factor (EGF) stimulation in human epidermoid carcinoma A431 cells. NF-IL6β was an immediate-early gene activated by the EGF-induced signaling pathways in cells. By using 5′-serial deletion reporter analysis, we showed that the region comprising the –347 to +9 base pairs was required for EGF response of the NF-IL6β promoter. This region contains putative consensus binding sequences of Sp1 and cAMP response element-binding protein (CREB). The NF-IL6β promoter activity induced by EGF was abolished by mutating the sequence of cAMP response element or Sp1 sites in the –347/+9 base pairs region. Both in vitro and in vivo DNA binding assay revealed that the CREB binding activity was low in EGF-starved cells, whereas it was induced within 30 min after EGF treatment of A431 cells. However, no change in Sp1 binding activity was found by EGF treatment. Moreover, the phosphatidylinositol 3 (PI3)-kinase inhibitor (wortmannin) and p38MAPK inhibitor (SB203580) inhibited the EGF-induced CREB phosphorylation and the expression of NF-IL6β gene in cells. We also demonstrated that CREB was involved in regulating the NF-IL6β gene transcriptional activity mediated by p38MAPK. Our results suggested that PI3-kinase/p38MAPK/CREB pathway contributed to the EGF activation of NF-IL6β gene expression.

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