Evidence Supporting Glial Derived TGF-B1 as a Modulator of Luteinizing Hormone-Releasing Hormone

Abstract

The overall objective of this research is to elucidate mechanisms involved in glial cell regulation of reproductive function. Regulation of LHRH secretion is a complex process that involves a multiplicity of inputs of both excitatory and inhibitory nature, and recent evidence has demonstrated the significance of glial cell-neuron interactions in modifying the activity of LHRH producing neurons. Evidence exists indicating that glial derived growth factors may play a role in the functional control o f the LHRH neuronal network as conditioned medium from astrocytes has been shown to stimulate LHRH secretion from immortalized LHRH neurons (52-55,57,58). However, there is a controversy concerning the identity of the active factor from astrocytes that is responsible for the LHRH releasing activity of conditioned medium. Melcangi and colleagues have provided evidence that TGF-Pi may be responsible for astrocyte-conditioned medium induced LHRH release in the GTl-l cell line (55). However, many of these studies supporting a role for TGF-pi were performed using cortical astrocytes, and additionally, no attempt was made to measure TGF-Pi levels in astrocyte-conditioned medium and correlate it to conditioned medium ability to induce LHRH release. Furthermore, these studies did not discuss potential regulators of TGF-pi secretion and also failed to investigate whether TGF-p receptors, which are necessary for TGF-pi action, are expressed in the GT1 cell line or hypothalamic tissue of the female rat (55,57,58). A second group suggests that TGF-a rather than TGF-Pi may be the active astrocyte factor that regulates LHRH release (53). Although TGF-a mRNA expression and precursor peptide immunoreactivity have been reported in the female rat hypothalamus, these studies failed to demonstrate the ability of hypothalamic astrocyte cultures to produce Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 15 TGF-a and relied upon addition of exogenous TGF-a to astrocyte cell cultures (50ng/ml 16 hours) in formation of astrocyte TGF-a-conditioned medium (25,46,52,53,76,77).