Interactions between type 1 astrocytes and LHRH-secreting neurons (GT1-1 cells):: modification of steroid metabolism and possible role of TGFβ1

The hypothesis that type 1 astrocytes (A1) might modify the activities of the enzymes 5 alpha-reductase (5 alpha-R) and 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) present in the GT1-1 cells has been tested. The data obtained indicate that, utilizing a co-culture technique, A1 are able to: (1) decrease the formation of dihydrotestosterone (DHT) from testosterone (T), (2) increase the formation of dihydroprogesterone (DHP) from progesterone (P); (3) decrease the conversion of DHP into tetrahydroprogesterone (THP) in GT1-1 cells. Moreover, GT1-1 cells are able to increase the formation of DHP in Al; that of DHT was unchanged. The present data might suggest the possible existence of a third isoform of the enzyme 5 alpha-R; details on this hypothesis are provided in the text. Interestingly, the inhibitory effect exerted by A1 on the formation of DHT in GT1-1 cells can be mimicked by transforming growth factor beta 1 (TGF beta 1). Since TGF beta 1 had been previously shown to be directly involved in the stimulatory control of LHRH secretion by GT1-1 cells, acting both on LHRH release [R.C. Melcangi, M. Galbiati, E. Messi, F. Piva, L. Martini, M. Motta, Type 1 astrocytes influence luteinizing hormone-releasing hormone release from the hypothalamic cell line GT1-1: is transforming growth factor-beta the principle involved? Endocrinology 136 (1995) 679-686.] and gene expression [M. Galbiati, M. Zanisi, E. Messi, I. Cavarretta, L. Martini, R.C. Melcangi, Transforming growth factor-beta and astrocytic conditioned medium influence LHRH gene expression in the hypothalamic cell line GT1, Endocrinology 137 (1996) 5605-5609], the present data also show that TGF beta 1 might intervene in modulating feedback signals reaching hypothalamic LHRH producing neurons. The present findings underline once more the importance of the physiological crosstalk between A1 and neurons. (C) 1999 Elsevier Science Ltd, All rights reserved.