Smad proteins are targets of transforming growth factor beta 1 in immortalised gonadotrophin-releasing hormone releasing neurones

Transforming growth factor beta (TGF beta) is one of the growth factors involved in the neuroendocrine control of the gonadotrophin-releasing hormone (GnRH) neurones. It is produced and released by the astrocytes surrounding GnRH neurones and directly controls their secretory activity. TGF beta signalling is based on a complex of two receptors that transduces the signal through peculiar intracellular substrates, the Smad proteins, which, upon activation, move into the nucleus, and modify the transcription of TGF beta responsive genes. The present study aimed to verify whether TGF beta 1 is able to regulate the Smad pathway in GT1-1 cells (i.e. an immortalised neuronal cell line releasing GnRH). We show that: (i) GT1-1 cells express Smad 2, 3, 4, and 7; (ii) TGF beta 1 enhances the phosphorylation of Smad 2 and 3 at short times of exposure (15-30 min); (iii) TGF beta 1 induces the synthesis of the inhibitory Smad 7 at longer times (60-120-240 min); (iv) the conditioned medium of type 1 astrocytes enhances the phosphorylation of Smad 2 and 3 in GT1-1 cells and a TGF beta 1 neutralising antibody counteracts this effect. The results indicate that Smads are targets of TGF beta 1 and that astrocytes are able to modulate Smads proteins in GT1-1 cells through the release of TGF beta 1. Taken together, the data provide new evidence that glial cells are important regulators of the GnRH neuronal activity.