Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2

Oral estrogen administration attenuates the metabolic action of growth hormone (GH) in humans. To investigate the mechanism involved, we studied the effects of estrogen on GH signaling through Janus kinase (JAK)2 and the signal transducers and activators of transcription (STATs) in HEK293 cells stably expressing the GH receptor (293GHR), HuH7 (hepatoma) and T-47D (breast cancer) cells. 293GHR cells were transiently transfected with an estrogen receptor-α expression plasmid and luciferase reporters with binding elements for STAT3 and STAT5 or the β-casein promoter. GH stimulated the reporter activities by four- to sixfold. Cotreatment with 17β-estradiol (E2) resulted in a dose-dependent reduction in the response of all three reporters to GH to a maximum of 49-66% of control at 100 nM (P < 0.05). No reduction was seen when E2 was added 1-2 h after GH treatment. Similar inhibitory effects were observed in HuH7 and T-47D cells. E2 suppressed GH-induced JAK2 phosphorylation, an effect attenuated by actinomycin D, suggesting a requirement for gene expression. Next, we investigated the role of the suppressors of cytokine signaling (SOCS) in E2 inhibition. E2 increased the mRNA abundance of SOCS-2 but not SOCS-1 and SOCS-3 in HEK293 cells. The inhibitory effect of E2 was absent in cells lacking SOCS-2 but not in those lacking SOCS-1 and SOCS-3. In conclusion, estrogen inhibits GH signaling, an action mediated by SOCS-2. This paper provides evidence for regulatory interaction between a sex steroid and the GH/JAK/STAT pathway, in which SOCS-2 plays a central mechanistic role

Interaction of the erythroid transcription factor cGATA-1 with a critical auto-regulatory element.

We have performed a mutational analysis of the promoter for the chicken erythroid-specific GATA-1 transcription factor, and have investigated in detail the interaction of the factor with an upstream auto-regulatory element (ARE). We find that a single proximal GATA binding site of the ARE is required for promoter activity in primary erythroid cells; however, this minimal promoter is inappropriately active in fibroblasts. At least two molecules of GATA-1 can interact with the ARE, and sequences outside of the consensus site appear critical for the transcriptional activity of the bound protein. Finally, we provide evidence for complex protein/DNA interactions at the ARE, including the ability of GATA-1 to bend DNA

Strain-related regional alterations of calcium-handling proteins in myocardial remodeling

BackgroundCardiac remodeling has been shown to have deleterious effects at both the global and local levels. The objective of this study is to investigate the role of strain in the initiation of structural and functional changes of myocardial tissue and its relation to alteration of calcium-handling proteins during cardiac remodeling after myocardial infarction.MethodsSixteen sonomicrometry transducers were placed in the left ventricular free wall of 9 sheep to measure the regional strain in the infarct, adjacent, and remote myocardial regions. Hemodynamic, echocardiographic, and sonomicrometry data were collected before myocardial infarction, after infarction, and 2, 6, and 8 weeks after infarction. Regional myocardial tissues were collected for calcium-handling proteins at the end study.ResultsAt time of termination, end-systolic strains in 3 regionally distinct zones (remote, adjacent, and infarct) of myocardium were measured to be −14.65 ± 1.13, −5.11 ± 0.60 (P ≤ .05), and 0.92 ± 0.56 (P ≤ .05), respectively. The regional end-systolic strain correlated strongly with the abundance of 2 major calcium-handling proteins: sarcoplasmic reticulum Ca2+ adenosine triphosphatase subtype 2a (r2 = 0.68, P ≤ .05) and phospholamban (r2 = 0.50, P ≤ .05). A lesser degree of correlation was observed between the systolic strain and the abundance of sodium/calcium exchanger type 1 protein (r2 = 0.17, P ≤ .05).ConclusionsRegional strain differences can be defined in the different myocardial regions during postinfarction cardiac remodeling. These differences in regional strain drive regionally distinct alterations in calcium-handling protein expression

Anatomical study of the pterygopalatine fossa using an endoscopic endonasal approach: spatial relations and distances between surgical landmarks

Object The pterygopalatine fossa is an area that lies deep within the skull base. The recent extensive use of the endoscopic endonasal approach has provided neurosurgeons with a method to reach various areas of the skull base through a less invasive approach than traditional transcranial or transfacial approaches. This study aims to provide neurosurgeons with new data concerning direct endoscopic measurements and precise anatomical topography features of the pterygopalatine fossa. Methods An anatomical dissection of six fixed cadaver heads (12 pterygopalatine fossae) was performed to analyze spatial relationships and distances between the most important neurovascular structures in this region, and to estimate the size of the endoscopic surgical field for operations in this area. The endoscopic endonasal approach offers direct access to the pterygopalatine fossa through its anteromedial walls. Conclusions Using an endoscopic endonasal approach makes it possible to identify all of the anatomical landmarks of the pterygopalatine fossa and almost all of the contiguous skull base areas