scholarly journals Progesterone Receptor Coregulators as Factors Supporting the Function of the Corpus Luteum in Cows

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 923
Author(s):  
Robert Rekawiecki ◽  
Karolina Dobrzyn ◽  
Jan Kotwica ◽  
Magdalena K. Kowalik
Keyword(s):  
Progesterone Receptor ◽  
Corpus Luteum ◽  
Estrous Cycle ◽  
Histone Acetyltransferase ◽  
Camp Response Element Binding ◽  
Target Cells ◽  
Expression Levels ◽  
Steroid Receptor Coactivator ◽  
Element Binding Protein ◽  
Coregulatory Proteins

Progesterone receptor (PGR) for its action required connection of the coregulatory proteins, including coactivators and corepressors. The former group exhibits a histone acetyltransferase (HAT) activity, while the latter cooperates with histone deacetylase (HDAC). Regulations of the coregulators mRNA and protein and HAT and HDAC activity can have an indirect effect on the PGR function and thus progesterone (P4) action on target cells. The highest mRNA expression levels for the coactivators—histone acetyltransferase p300 (P300), cAMP response element-binding protein (CREB), and steroid receptor coactivator-1 (SRC-1)—and nuclear receptor corepressor-2 (NCOR-2) were found in the corpus luteum (CL) on days 6 to 16 of the estrous cycle. The CREB protein level was higher on days 2–10, whereas SRC-1 and NCOR-2 were higher on days 2–5. The activity of HAT and HDAC was higher on days 6–10 of the estrous cycle. All of the coregulators were localized in the nuclei of small and large luteal cells. The mRNA and protein expression levels of the examined coactivators and corepressor changed with the P4 level. Thus, P4 may regulate CL function via the expression of coregulators, which probably affects the activity of the PGR.

scholarly journals The Src Kinase Pathway Promotes Tamoxifen Agonist Action in Ishikawa Endometrial Cells through Phosphorylation-Dependent Stabilization of Estrogen Receptor α Promoter Interaction and Elevated Steroid Receptor Coactivator 1 Activity

2005 ◽  
Vol 19 (3) ◽  
pp. 732-748 ◽  
Author(s):  
Yatrik M. Shah ◽  
Brian G. Rowan
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Binding Protein ◽  
Src Kinase ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Steroid Receptor Coactivator ◽  
Agonist Action ◽  
Element Binding Protein ◽  
Promoter Interaction

Abstract Tamoxifen is the most widely used selective estrogen receptor modulator for breast cancer in clinical use today. However, tamoxifen agonist action in endometrium remains a major hurdle for tamoxifen therapy. Activation of the nonreceptor tyrosine kinase src promotes tamoxifen agonist action, although the mechanisms remain unclear. To examine these mechanisms, the effect of src kinase on estrogen and tamoxifen signaling in tamoxifen-resistant Ishikawa endometrial adenocarcinoma cells was assessed. A novel connection was identified between src kinase and serine 167 phosphorylation in estrogen receptor (ER)-α via activation of AKT kinase. Serine 167 phosphorylation stabilized ER interaction with endogenous ER-dependent promoters. Src kinase exhibited the additional function of potentiating the transcriptional activity of Gal-steroid receptor coactivator 1 (SRC-1) and Gal-cAMP response element binding protein-binding protein in endometrial cancer cells while having no effect on Gal-p300-associated factor and Gal fusions of the other p160 coactivators glucocorticoid-interacting protein 1 (transcriptional intermediary factor 2/nuclear coactivator-2/SRC-2) and amplified in breast cancer 1 (receptor-associated coactivator 3/activator of transcription of nuclear receptor/SRC-3). Src effects on ER phosphorylation and SRC-1 activity both contributed to tamoxifen agonist action on ER-dependent gene expression in Ishikawa cells. Taken together, these data demonstrate that src kinase potentiates tamoxifen agonist action through serine 167-dependent stabilization of ER promoter interaction and through elevation of SRC-1 and cAMP response element binding protein-binding protein coactivation of ER.

scholarly journals Effects of Ketamine on Learning and Memory in the Hippocampus of Rats through ERK, CREB, and Arc

2020 ◽  
Vol 11 (1) ◽  
pp. 27
Author(s):  
Mingxian Shi ◽  
Jiafeng Ding ◽  
Lin Li ◽  
Hui Bai ◽  
Xinran Li ◽  
...  
Keyword(s):  
Protein Expression ◽  
Learning And Memory ◽  
Dose Group ◽  
Camp Response Element Binding ◽  
Morris Water Maze Test ◽  
Memory Ability ◽  
Expression Levels ◽  
Element Binding Protein ◽  
High Level ◽  
Arc Gene

Ketamine has become a popular recreational drug due to its neuronal anesthesia effect and low price. The process of learning and memory is part of the distinctive high-level neural activities in animals. We investigated the effects of subanesthetic and anesthetic doses of ketamine on the learning and memory-related signal transduction mechanisms. We used the Morris water maze test to execute rats’ learning and memory ability and detected changes of Arc mRNA and Arc, cAMP-response element-binding protein (CREB), phospho-CREB (p-CREB), extracellular signal-regulated kinase (ERK), and phospho-ERK (p-ERK) protein expression in the hippocampus 10 min and 24 h after administration. Ten min after ketamine injection, the Arc gene and the protein expression levels increased in all groups; p-ERK only increased in the chronic subanesthetic dose group. After 24 h, the Arc gene and the protein expression levels of the subanesthetic dose group increased, but those of the chronic subanesthetic dose group and anesthetic dose group decreased. However, p-ERK increased in all groups. A chronic subanesthetic dose of ketamine could increase learning and memory ability through ERK, CREB, and Arc in a short time, and the high body temperature after the subanesthetic dose of ketamine injection was the main factor leading to changes in Arc. The subanesthetic dose of ketamine regulated learning and memory through ERK, CREB, and ARC 24 h after injection.

scholarly journals Changes in the Levels of Progesterone Receptor mRNA and Protein in the Bovine Corpus Luteum During the Estrous Cycle

2010 ◽  
Vol 56 (2) ◽  
pp. 219-222 ◽  
Author(s):  
Ryosuke SAKUMOTO ◽  
Margarete VERMEHREN ◽  
Rebecca A.-M. KENNGOTT ◽  
Kiyoshi OKUDA ◽  
Fred SINOWATZ
Keyword(s):  
Progesterone Receptor ◽  
Corpus Luteum ◽  
Estrous Cycle ◽  
Receptor Mrna ◽  
Bovine Corpus Luteum

scholarly journals Differential Utilization of Transcription Activation Subdomains by Distinct Coactivators Regulates Pit-1 Basal and Ras Responsiveness

2007 ◽  
Vol 21 (1) ◽  
pp. 172-185 ◽  
Author(s):  
Dawn L. Duval ◽  
Matthew D. Jonsen ◽  
Scott E. Diamond ◽  
Patience Murapa ◽  
Annie Jean ◽  
...  
Keyword(s):  
Binding Protein ◽  
Transcription Activation ◽  
Camp Response Element Binding ◽  
Dual Function ◽  
Specific Gene ◽  
Activation Domain ◽  
Steroid Receptor Coactivator ◽  
Ras Activation ◽  
Element Binding Protein ◽  
Domain Insertion

Abstract The POU-homeodomain transcription factor Pit-1 governs ontogeny and cell-specific gene expression of pituitary lactotropes, somatotropes, and thyrotropes. The splice isoform, Pit-1β, inserts a 26-amino acid (AA) repressor at AA48 in the Pit-1 transcription activation domain (TAD). The Pit-1 TAD contains a basal regulatory subregion, R1 (AA1–45), and a basal and Ras-responsive region, R2 (AA46–80). To precisely map these activities, we generated GAL4-Pit-1/Pit-1βTAD fusions and, in full-length HA-Pit-1, a series of substitution mutants of R2. Analysis in GH4 cells identified an activation domain at AA50–70, followed by an overlapping, dual-function, Ras-responsive-inhibitory domain, located from AA60–80. In contrast, GAL4-Pit-1βTAD repressed both basal and Ras-mediated TAD activity. To determine the functional interplay between TAD subregions and the β-domain, we inserted the β-domain every 10 AA across the 80-AA Pit-1 TAD. Like wild-type Pit-1β, each construct retained transcriptional activity in HeLa cells and repressed the Ras response in GH4 cells. However, β-domain insertion at AA61 and 71 resulted in greater repression of Ras responsiveness, defining a critical R2 TAD spanning AA61–71 of Pit-1. Furthermore, Ras activation is augmented by steroid receptor coactivator 1, whereas cAMP response element binding protein-binding protein is not a Ras mediator in this system. In summary, the Pit-1/Pit-1β TADs are composed of multiple, modular, and transferable subdomains, including a regulatory R1 domain, a basal activation region, a selective inhibitory-Ras-responsive segment, and a β-specific repressor domain. These data provide novel insights into the mechanisms by which the Pit-1 TAD integrates DNA binding, protein partner interactions, and distinct signaling pathways to fine-tune Pit-1 activity.

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.

The transcriptional activity of Pygopus is enhanced by its interaction with cAMP-response-element-binding protein (CREB)-binding protein

2009 ◽  
Vol 422 (3) ◽  
pp. 493-501 ◽  
Author(s):  
Phillip G. P. Andrews ◽  
Zhijian He ◽  
Cathy Popadiuk ◽  
Kenneth R. Kao
Keyword(s):  
Histone Acetylation ◽  
Transcriptional Activation ◽  
Transcriptional Activity ◽  
Target Genes ◽  
Histone Acetyltransferase ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Creb Binding Protein ◽  
Hek 293 ◽  
Element Binding Protein

Pygopus is a core component of the β-catenin/TCF (T-cell factor) transcriptional activation complex required for the expression of canonical Wnt target genes. Recent evidence suggests that Pygopus could interpret histone methylation associated with target genes and it was shown to be required for histone acetylation. The involvement of a specific acetyltransferase, however, was not determined. In this report, we demonstrate that Pygopus can interact with the HAT (histone acetyltransferase) CBP [CREB (cAMP-responsive-element-binding protein)-binding protein]. The interaction is via the NHD (N-terminal homology domain) of Pygopus, which binds to two regions in the vicinity of the HAT domain of CBP. Transfected and endogenous hPygo2 (human Pygopus2) and CBP proteins co-immunoprecipitate in HEK-293 (human embryonic kidney 293) cells and both proteins co-localize in SW480 colorectal cancer cells. The interaction with CBP also enhances both DNA-tethered and TCF/LEF1 (lymphoid enhancing factor 1)-dependent transcriptional activity of Pygopus. Furthermore, immunoprecipitated Pygopus protein complexes displayed CBP-dependent histone acetyltransferase activity. Our data support a model in which the NHD region of Pygopus is required to augment TCF/β-catenin-mediated transcriptional activation by a mechanism that includes both transcriptional activation and histone acetylation resulting from the recruitment of the CBP histone acetyltransferase.

scholarly journals TGFB1 represses the expression of SF1 and LRH1 to inhibit E2 production in rat LCs

Reproduction ◽  
2017 ◽  
Vol 153 (5) ◽  
pp. 621-629 ◽  
Author(s):  
Qianqian Yang ◽  
Binfang Ma ◽  
Huilian Qiao ◽  
He Ma ◽  
Yuhang Dong ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Camp Response Element Binding ◽  
Steroidogenic Factor 1 ◽  
Expression Levels ◽  
Rat Testis ◽  
Germ Cell Differentiation ◽  
Element Binding Protein ◽  
Responsive Element

Leydig cells (LCs) in the adult testis have been identified as the major sites of oestrogen production, which is crucial for mammalian germ cell differentiation. Our previous work showed that transforming growth factor beta 1 (TGFB1) inhibits estradiol (E2) secretion via down-regulating Cyp19 gene expression in mature rat LCs. However, the mechanism remains unclear. In the present study, the effects of TGFB1 on the expression levels of steroidogenic factor 1 (SF1), liver receptor homolog 1 (LRH1), cAMP response element-binding protein (CREB) and cAMP responsive element modulator (CREM) were evaluated both in primary cultured LCs and in rat testis. The involvement of TGFB1 signalling in the regulation of SF1 and LRH1 expression was then validated by applying the inhibitor of the TGFB type 1 receptor (TGFBR1) SB431542. Moreover, the expression of CYP19 in testicular LCs was investigated and the production of E2 in testicular interstitial fluid (TIF) was measured. The results showed that TGFB1 especially down-regulated the expression levels of SF1 and LRH1 both in primary cultured LCs and in rat testis. The down-regulations of TGFB1 in the production of E2 in TIF and the expression of CYP19 in testicular LCs were also observed in vivo. These inhibitory effects could be reversed by TGFBR1 inhibitor SB431542. Our findings suggest that TGFB1 may act through the canonical signalling pathway involving ALK5 to restrain SF1 and LRH1 accumulation and eventually attenuate Cyp19 transcription and oestrogen production in LCs.

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