Cell Cycle Regulators and Lineage-Specific Therapeutic Targets for Cushing Disease

Cell cycle proteins are critical to pituitary development, but their contribution to lineage-specific tumorigenesis has not been well-elucidated. Emerging evidence from in vitro human tumor analysis and transgenic mouse models indicates that G1/S-related cell cycle proteins, particularly cyclin E, p27, Rb, and E2F1, drive molecular mechanisms that underlie corticotroph-specific differentiation and development of Cushing disease. The aim of this review is to summarize the literature and discuss the complex role of cell cycle regulation in Cushing disease, with a focus on identifying potential targets for therapeutic intervention in patients with these tumors

Rosiglitazone and Pioglitazone Alter Aromatase Kinetic Properties in Human Granulosa Cells

We have previously reported that, in human granulosa cells, thiazolidinediones rosiglitazone and pioglitazone inhibit estrogen synthesis by interfering with androgen binding to aromatase, without an effect on aromatase mRNA or protein expression. In the current paper, we explore the effects of rosiglitazone and pioglitazone on the aromatase enzyme kinetic properties in human granulosa cells. The cells were incubated with various concentrations of testosterone or androstenedione, with or without rosiglitazone or pioglitazone. Estradiol and estrone concentrations in the conditioned tissue culture medium were measured by radioimmunoassay or immunosorbent assay. When testosterone was used as substrate, rosiglitazone or pioglitazone inhibited the Vmax by 35% (P < 0.001) and 24% (P < 0.001), respectively. When androstenedione was used as substrate, both rosiglitazone or pioglitazone inhibited Vmax by 13% (P < 0.007). We conclude that rosiglitazone or pioglitazone has no effect on Km but inhibits Vmax of aromatase in human granulosa cells, therefore, acting as noncompetitive inhibitors

Memory-related gene expression profile of the male rat hippocampus induced by teeth extraction and occlusal support recovery

Objectives: The present study aimed to identify the effect of memory-related genes on male rats tested for spatial memory with either molar teeth extraction or its restoration by occlusal support using experimental dentures. Design: Memory-related genes were detected from hippocampi of male Wistar rats (exposed to teeth extraction with or without dentures, or no extraction (control)) (7-week old) after behavioural testing (via the radial maze task) using a DNA microarray. The time course of the expression of these genes was evaluated by quantitative real-time polymerase chain reaction (PCR) (on 49-week-old rats). Results: In preliminary experiments, to determine which memory genes are affected by spatial memory training, DNA microarray analysis revealed that thyrotropin-releasing hormone (Trh) and tenascin XA (Tnxa) were up-regulated and neuronatin (Nnat) and S100a9 were down-regulated after the maze training. The expression of Tnxa, Nnat and S100a9 of 49-week-old rats (during the time course) via quantitative real-time PCR was consistent with the results of microarrays of the preliminary experiment. Expression of Trh that was evaluated by quantitative real-time PCR did not agree with the results for this gene from the microarray for all groups. Therefore, expression of Trh may have increased in only young, trained rats. The expression of S100a9 prior to the maze task was down-regulated in only the extraction group. Conclusion: These results demonstrated that Trh, Tnxa and Nnat genes were affected according to the degree of memory in male rats. This study also indicated that S100a9 is a memory-related gene, which is affected by the presence of occlusal support

Bromocriptine approved as the first medication to target dopamine activity to improve glycemic control in patients with type 2 diabetes

Michael A Via1, Himani Chandra2, Takako Araki1, Matthew V Potenza3, Maria Skamagas41Division of Endocrinology and Metabolism, Albert Einstein College of Medicine, Beth Israel Medical Center, New York, NY, USA; 2Division of Endocrinology, Diabetes and Bone Disease, Mount Sinai School of Medicine, James J Peters VA Medical Center, New York, NY, USA; 3Diabetes and Endocrinology, West Nyack, New York, NY, USA; 4Division of Endocrinology, Diabetes and Bone Disease, Mount Sinai School of Medicine, New York, NY, USAAbstract: Type 2 diabetes mellitus (T2DM) continues to rise in prevalence in the United States and worldwide. Despite advances in medical treatments for T2DM, many patients remain uncontrolled. By targeting centrally mediated pathways of glucose metabolism, bromocriptine represents a novel therapeutic option in T2DM. Several small clinical trials demonstrate improvements in insulin resistance and glycemic control. After the submission of data from four recent, large clinical trials, the US Food and Drug Administration has approved the use of bromocriptine in T2DM. We review the available data from these four trials and other published studies. Bromocriptine is a promising therapy for diabetes patients and demonstrates modest improvements in glycemic control.Keywords: bromocriptine, dopamine agonists, diabetes, glycemic contro