Expression and differential effects of the activation of glucocorticoid receptors in mouse gonadotropin-releasing hormone neurons.
Prenatal exposure of rodents to glucocorticoids (Gc) affects the sexual development of the offspring, possibly interfering with the differentiation of the hypothalamic-pituitary-gonadal axis. Glucocorticoid receptors (GR) are present on gonadotropin-releasing hormone (GnRH) neurons in the rat hypothalamus, suggesting a direct effect of Gc in the control of the synthesis and/or release of the hormone. In this study, we demonstrate the colocalization of immunoreactive GR with GnRH in a subpopulation of mouse hypothalamic GnRH neurons, confirming the possible involvement of Gc in mouse GnRH neuronal physiology. Receptor-binding assay, RT-PCR, immunocytochemistry, and immunoblotting experiments carried out in GN11 immortalized GnRH neurons show the presence of GR even in the more immature mouse GnRH neurons and confirm the expression of GR in GT1-7 mature GnRH cells. In GN11 cells, the activation of GR with dexamethasone produces nuclear translocation, but does not lead to the inhibition of GnRH gene expression already reported in GT1-7 cells. Long-term exposure of GN11 cells to dexamethasone induces an epithelial-like phenotype with a reorganization of F-actin in stress fibers. Finally, we found that Gc treatment significantly decreases the migratory activity in vitro and the levels of phosphorylated focal adhesion kinase of GN11 immature neurons. In conclusion, these data indicate that GR are expressed in mouse hypothalamic GnRH neurons in vivo as well as in the immature GN11 GnRH neurons in vitro. Moreover, the effects of the GR activation in GN11 and in GT1-7 cells may be related to the neuronal maturational stage of the two cell lines, suggesting a differential role of Gc in neuronal development.
Department of Endocrinology, Center of Excellence on Neurodegenerative Diseases, Milan, Italy.
Donatella
D
Dondi
Margherita
M
Piccolella
Elio
E
Messi
Marek
M
Demissie
Anna
A
Cariboni
Silvia
S
Selleri
Flavio
F
Piva
Athina
A
Samara
G Giacomo
GG
Consalez
Roberto
R
Maggi
D000367:Age Factors; D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000187:drug effects / Q000378:metabolism*; D007031:Hypothalamus / Q000254:growth & development / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D007987:Gonadotropin-Releasing Hormone; D003907:Dexamethasone