Estrogen-astrocyte-luteinizing hormone-releasing hormone signaling: a role for 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 conditioned 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 3alpha-hydroxy-5alpha-pregnane-20-one (3alpha, 5alpha-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. Ultrafiltration to remove peptides with molecular weights >10 kDa virtually abolished the LHRH-releasing ability of the HA CM. Furthermore, immunoneutralization with a panspecific THF-beta antibody dose-dependently attenuated the LHRH-releasing activity of the CM. Rat hypothalamus and GT1-7 cells were demonstrated to express TGF-beta receptors as well as furin, an enzyme that converts latent TGF-beta(1) to active TGF-beta(1). Estrogen receptor-alpha and ER-beta mRNA and protein were also demonstrated in HAs by reverse transcription-polymerase chain reaction and double immunofluorescence, and treatment with 17beta-estradiol (17beta-E(2)) increased both active and latent TGF-beta(1) levels in HA CM. The effect of 17beta-E(2) was completely blocked by the ER antagonist ICI8280. As a whole, these studies provide evidence of a previously undescribed 17beta-E(2)-TGF-beta(1)-LHRH signaling pathway.
Buchanan
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CD
Department of Physiology & Endocrinology, School of Medicine, Medical College of Georgia, Augusta, Georgia 30912-3000, USA.
Mahesh
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VB
Brann
D W
DW
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001253:Astrocytes / Q000378:metabolism*; D002460:Cell Line; D002461:Cell Line, Transformed; D017077:Culture Media, Conditioned / Q000737:chemistry; D004958:Estradiol / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000166:cytology; D009457:Neuroglia / Q000378:metabolism; D011280:Pregnanolone / Q000031:analogs & derivatives / Q000032:analysis / Q000494:pharmacology; D051381:Rats; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D014462:Ultrafiltration
D000906:Antibodies; D017077:Culture Media, Conditioned; D016212:Transforming Growth Factor beta; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D011280:Pregnanolone