Interactions between type 1 astrocytes and LHRH-secreting neurons (GT1-1 cells): modification of steroid metabolism and possible role of TGFbeta1.
The hypothesis that type 1 astrocytes (A1) might modify the activities of the enzymes 5alpha-reductase (5alpha-R) and 3alpha-hydroxysteroid dehydrogenase (3alpha-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 A1; that of DHT was unchanged. The present data might suggest the possible existence of a third isoform of the enzyme 5alpha-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 beta1 (TGFbeta1). Since TGFbeta1 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 TGFbeta1 might intervene in modulating feedback signals reaching hypothalamic LHRH producing neurons. The present findings underline once more the importance of the physiological cross-talk between A1 and neurons.
Cavarretta
I
I
Department of Endocrinology, University of Milan, Italy.
Magnaghi
V
V
Ferraboschi
P
P
Martini
L
L
Melcangi
R C
RC
D004092:20-alpha-Dihydroprogesterone / Q000378:metabolism; D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D013196:Dihydrotestosterone / Q000378:metabolism; D005043:Etiocholanolone / Q000031:analogs & derivatives / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011280:Pregnanolone / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013256:Steroids / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology
D013256:Steroids; D016212:Transforming Growth Factor beta; D013196:Dihydrotestosterone; D004092:20-alpha-Dihydroprogesterone; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D011374:Progesterone; C006576:androstane-3,17-dione; D005043:Etiocholanolone; D011280:Pregnanolone; D015096:3-Hydroxysteroid Dehydrogenases; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase