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

The hypothesis that type 1 astrocytes (A1) might modify the activities of t he enzymes 5 alpha-reductase (5 alpha-R) and 3 alpha-hydroxysteroid dehydro genase (3 alpha-HSD) present in the GT1-1 cells has been tested. The data o btained 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 p ossible existence of a third isoform of the enzyme 5 alpha-R; details on th is hypothesis are provided in the text. Interestingly, the inhibitory effec t exerted by A1 on the formation of DHT in GT1-1 cells can be mimicked by t ransforming growth factor beta 1 (TGF beta 1). Since TGF beta 1 had been pr eviously shown to be directly involved in the stimulatory control of LHRH s ecretion by GT1-1 cells, acting both on LHRH release [R.C. Melcangi, M. Gal biati, E. Messi, F. Piva, L. Martini, M. Motta, Type 1 astrocytes influence luteinizing hormone-releasing hormone release from the hypothalamic cell l ine GT1-1: is transforming growth factor-beta the principle involved? Endoc rinology 136 (1995) 679-686.] and gene expression [M. Galbiati, M. Zanisi, E. Messi, I. Cavarretta, L. Martini, R.C. Melcangi, Transforming growth fac tor-beta and astrocytic conditioned medium influence LHRH gene expression i n the hypothalamic cell line GT1, Endocrinology 137 (1996) 5605-5609], the present data also show that TGF beta 1 might intervene in modulating feedba ck signals reaching hypothalamic LHRH producing neurons. The present findin gs underline once more the importance of the physiological crosstalk betwee n A1 and neurons. (C) 1999 Elsevier Science Ltd, All rights reserved.