Transforming Growth Factor β1 (TGF-β1) is a well-known neuroprotective and neurotrophic factor demonstrated to play a role in synaptic transmission. However, its involvement in physiological mechanisms underlying synaptic plasticity and memory at hippocampal level has not been thoroughly investigated. Here, we examine the role of TGF-β1 in hippocampal long-term potentiation (LTP) and memory in adult wild type mice. Our data provide evidence that administration of exogenous TGF-β1 is able to convert early-phase-LTP into late-phase-LTP. Furthermore, we show that the block of the endogenous TGF-β1 signaling pathway by the specific TGF-β1 inhibitor SB431542, impairs LTP and object recognition memory. The latter impairment was rescued by administration of exogenous TGF-β1, suggesting that endogenously produced TGF-β1 plays a role in physiological mechanisms underlying LTP and memory. Finally, TGF-β1 functional effect correlates with an increased expression of the phosphorylated transcription factor cAMP-Responsive Element Binding protein.

Objective: The objective of the study was to evaluate the expression and functional activity of Peroxisome proliferator-activated receptor (PPAR) g in pituitary adenomas from 14 consecutive acromegalic patients and to establish its role in apoptosis. Subjects and methods: Fourteen consecutive acromegalic patients were enrolled in the study. Wistar-Furth rats were used for in vivo studies. Expression of PPARg was evaluated by RT-PCR and Western blot. Apoptosis and cell cycle were assessed by FACS analysis. The effects of PPARg ligands on transcriptional regulation of GH gene were evaluated by RT-PCR and electromobility shift assay. Results: PPARg was expressed in all human GH-secreting adenoma (GH-oma), in normal pituitary tissue samples (39^24% and 78^5% of immunostained nuclei respectively; P , 0.0002; ANOVA), and in rat GH-secreting (GH3) cells. A PPRE-containing reporter plasmid transfected into GH3 cells was activated by ciglitazone or rosiglitazone (TZDs), indicating that PPARg was functionally active. Treatment of GH3 cells with TZDs increased apoptosis in a dose-dependent manner (P ¼ 0.0003) and arrested cell proliferation, reducing the number of cells in the S-phase (P , 0.0001 vs untreated cells). TZDs increased the expression of TRAIL, leaving unaffected that of p53 and Bax. TZDs reduced GH concentrations in the culture media from 43.7^5.4 ng/ml to 2.1^0.3 ng/ml (P , 0.0001) and in cell extracts (P , 0.004). PPARg-RXRa heterodimers bound to GH promoter, inhibiting its activity and reducing GH mRNA levels (1.8 £ 10 6 vs 5.7 £ 10 6 transcripts respectively vs untreated cells; P , 0.002). Subcutaneous GH-oma developed in rats injected with GH3 cells; tumor growth increased in placebo-treated rats and to a lesser extent in TZDs-treated animals (24.1^2.0 g, and 14.8^4.2 g respectively, P , 0.03). Serum GH concentrations were lower in TZDs-treated rats than in controls (871^67 ng/ml vs 1.309^238 ng/ml; P , 0.05). Conclusions:The results of this study indicate that PPARg controls GH transcription and secretion as well as apoptosis and growth of GH-oma; thus, TZDs have the potential of a useful tool in the complex therapeutic management of acromegalic patients.

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PDRN seemed to promote proliferation of human pre-adipocytes at both passages, but cell population growth increased in pre-adipocyte at P16, after 9 days as compared to control. Our data suggest that PDRN could act as a pre-adipocyte growth stimulator.

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