ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2004) 7 P189

TGFbeta signaling pathways in LHRH neurons

M Galbiati, S Saredi & RC Melcangi

Department of Endocrinology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Milano, Italy.

Observations obtained in our and other laboratories suggest that growth factors produced by glial cells, may participate in the control of LHRH-secreting neurons. In particular, utilizing GT1 cells (i.e., LHRH immortalized neurons) we have demonstrated, that transforming growth factor beta 1 (TGFbeta 1) is able to modulate the synthesis and release of LHRH from these neurons. We presently investigate the mechanism of action of this growth factor analyzing TGFbeta signaling pathways in GT1 cells. Our data indicate that these cells express: a) the two functional TGFbeta receptors (RI and RII); b) Smad 2, 3 and 4, which are necessary to transduce the TGFbeta signal from the receptors to the nucleus; and c) Smad 7, which is necessary to turn off the signal of TGFbeta. By a quantitative RT-PCR approach we then demonstrate that, in GT1 cells, Smad 7 mRNA levels are stimulated by TGFbeta 1 exposure. In particular, mRNA levels for this Smad are increased after 1, 2 and 4 h of treatment with TGFbeta 1 (5 ng/ml). Smad 2 mRNA levels are unchanged after these times of exposure, but, as demonstrated by Western blot analysis, phosphorylation of Smad 2 is evident after 15 and 30 min of treatment with TGFbeta 1. The fact that LHRH gene might be considered directly responsive to TGFbeta, via an activation of Smad signaling, is also supported by a computer analysis, which shows that repeated copies of the optimal Smad Binding Element sequence (5'-AGAC-3') are present in the promoter region of the LHRH gene of different species. Altogether, the present observations further extend our knowledge on the control exerted by this growth factor on LHRH neurons. (Financial support: QLK6-CT-2000-00179)

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