TY - JOUR
T1 - Estrogen-astrocyte-luteinizing hormone-releasing hormone signaling
T2 - A role for transforming growth factor-β1
AU - Buchanan, C. D.
AU - Mahesh, V. B.
AU - Brann, D. W.
PY - 2000
Y1 - 2000
N2 - 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-β1 (TGF-β1) and 3α-hydroxy-5α-pregnane-20-one (3α,5α- 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- α 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-β antibody dose-dependently attenuated the LHRH-releasing activity of the CM. Rat hypothalamus and GT1-7 cells were demonstrated to express TGF-β receptors as well as furin, an enzyme that converts latent TGF-β1 to active TGF-β1. Estrogen receptor-α and ER-β mRNA and protein were also demonstrated in HAs by reverse transcription-polymerase chain reaction and double immunofluorescence, and treatment with 17β-estradiol (17β-E2) increased both active and latent TGF-β1 levels in HA CM. The effect of 17β-E2 was completely blocked by the ER antagonist IC18280. As a whole, these studies provide evidence of a previously undescribed 17β-E2-TGF-β1- LHRH signaling pathway.
AB - 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-β1 (TGF-β1) and 3α-hydroxy-5α-pregnane-20-one (3α,5α- 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- α 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-β antibody dose-dependently attenuated the LHRH-releasing activity of the CM. Rat hypothalamus and GT1-7 cells were demonstrated to express TGF-β receptors as well as furin, an enzyme that converts latent TGF-β1 to active TGF-β1. Estrogen receptor-α and ER-β mRNA and protein were also demonstrated in HAs by reverse transcription-polymerase chain reaction and double immunofluorescence, and treatment with 17β-estradiol (17β-E2) increased both active and latent TGF-β1 levels in HA CM. The effect of 17β-E2 was completely blocked by the ER antagonist IC18280. As a whole, these studies provide evidence of a previously undescribed 17β-E2-TGF-β1- LHRH signaling pathway.
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U2 - 10.1095/biolreprod62.6.1710
DO - 10.1095/biolreprod62.6.1710
M3 - Article
C2 - 10819775
AN - SCOPUS:0034127135
SN - 0006-3363
VL - 62
SP - 1710
EP - 1721
JO - Biology of reproduction
JF - Biology of reproduction
IS - 6
ER -