Astrocyte-neuron interactions in vitro: role of growth factors and steroids on LHRH dynamics

The data here reviewed, obtained with in vitro models, indicate that growth factors and steroids play a significant role in astrocyte-neuron interactions. Different designs have been adopted: (1) GT1-1 cells (a cell line derived from a mouse hypothalamic LHRH-producing tumor) were cocultured with type 1 rat astrocytes; and (2) GT1-1 cells were exposed to the conditioned medium (CM) in which type 1 rat astrocytes had been grown for 24 h. LHRH release and mRNA LHRH levels were measured respectively in the medium and in cell homogenates, at different time intervals (LHRH release, by RIA; LHRH mRNA by Northern blot analysis). The data obtained show that type 1 astrocytes secrete in the medium TGFbeta, which is able to modulate the release and the gene expression of LHRH in GT1-1 cells; and that one or more LHRH-degrading enzymes is/are present in the conditioned medium of type 1 astrocytes. A second part of the experiments have indicated that type 1 astrocytes are also able to affect, in different directions, the metabolism of testosterone and progesterone into their 5alpha-reduced metabolites occurring in the GT1-1 cells. In particular, it has been observed that the conversion of testosterone into DHT is decreased by the coculture with type 1 astrocytes, while the conversion of progesterone into DHP is increased by the same coculture conditions. Moreover, type 1 astrocytes are sensitive to steroid hormones, and in particular to the 5alpha-reduced metabolites of progesterone; this has been shown by analyzing the effects exerted by different steroids on the gene expression of the typical astrocyte marker GFAP.