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 g rowth 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) wer e cocultured with type 1 rat astrocytes; and (2) GT1-1 cells were expo sed 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 r espectively in the medium and in cell homogenates, at different time i ntervals (LHRH release, by RIA; LHRH mRNA by Northern blot analysis). The data obtained show that type 1 astrocytes secrete in the medium TG F beta, 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 testostero ne and progesterone into their 5 alpha-reduced metabolites occurring i n the GT1-1 cells. In particular, it has been observed that the conver sion of testosterone into DHT is decreased by the coculture with type 1 astrocytes, while the conversion of progesterone into DHP is increas ed by the same coculture conditions. Moreover, type 1 astrocytes are s ensitive to steroid hormones, and in particular to the 5 alpha-reduced metabolites of progesterone; this has been shown by analyzing the eff ects exerted by different steroids on the gene expression of the typic al astrocyte marker GFAP. (C) 1997 Elsevier Science Inc.