Estrogen-astrocyte-luteinizing hormone-releasing hormone signaling: A rolefor transforming growth factor-beta(1)

The purpose of this study was to identify factors from astrocytes that can regulate LHRH neurosecretion. Exposure of LHRH-secreting (GT1-7) cells to c onditioned media (CM) from C6 glial cells and hypothalamic astrocytes (HA) stimulated LHRH release. Assays of C6 and HA CM revealed that transforming growth factor-beta(1) (TGF-beta(1)) and 3 alpha-hydroxy-5 alpha-pregnane-20 -one (3 alpha,5 alpha-THP), both known LHRH secretagogues, were present in CM and their levels increased in parallel to the LHRH-releasing activity of CM. In contrast, TGF-alpha was undetectable in C6 or HA CM. Ultrafiltratio n to remove peptides with molecular weights >10 kDa virtually abolished the LHRH-releasing ability of the HA CM. Furthermore, immunoneutralization wit h a panspecific THF-beta antibody dose-dependently attenuated the LHRH-rele asing activity of the CM. Rat hypothalamus and GT1-7 cells were demonstrate d to express TGF-beta receptors as well as furin, an enzyme that converts l atent TGF-beta(1) to active TGF-B-1. Estrogen receptor-alpha and ER-beta mR NA and protein were also demonstrated in HAs by reverse transcription-polym erase chain reaction and double immunofluorescence, and treatment with 17 b eta-estradiol (17 beta-E-2) increased both active and latent TGF-beta(1) le vels in HA CM. The effect of 17 beta-E-2 was completely blocked by the ER a ntagonist ICI8280. As a whole, these studies provide evidence of a previous ly undescribed 17 beta-E-2-TGF-beta(1)-LHRH signaling pathway.