Activin-A modulates gonadotropin-releasing hormone secretion from a gonadotropin-releasing hormone-secreting neuronal cell line.
The recent development of GnRH-secreting neuronal cell lines (GT1-1, GT1-3 and GT1-7 clones) has provided a model system for the study of the neural regulation of GnRH expression and secretion. We report here that activin-A stimulates GnRH secretion by GT1-7 cells in a dose-dependent manner, with an EC50 of approximately 2.5 ng/ml. The maximal response (50% stimulation) was achieved after 2 days of incubation with 20 ng/ml activin-A. Activin-A treatment increased total GnRH (secreted + cellular) in GT1-7 cells, possibly reflecting a stimulation of GnRH biosynthetic rates. The secretory effect of activin-A was also accompanied by a change in the cellular morphology to a more neuronal phenotype. The addition of TGF-beta (10 ng/ml), which is structurally related to activins, did not significantly increase secretion of GnRH by GT1-7 cells illustrating the specificity of the activin effect on this cell line. Although inhibin (20 ng/ml) alone did not directly affect the spontaneous secretion of GnRH, it was able to partially block the stimulatory effect of activin. The present study with the GT1-7 clonal cell line suggests that activin, and perhaps inhibin, might act at hypothalamic sites to regulate reproduction through the control of GnRH production and/or secretion.
González-Manchón
C
C
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, Calif.
Bilezikjian
L M
LM
Corrigan
A Z
AZ
Mellon
P L
PL
Vale
W
W
D028341:Activins; D002460:Cell Line; D002999:Clone Cells / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007265:Inhibins / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D011863:Radioimmunoassay; D012098:Reproduction / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology*
D016212:Transforming Growth Factor beta; D028341:Activins; D007987:Gonadotropin-Releasing Hormone; D007265:Inhibins