Expression and function of gonadotropin-releasing hormone (GnRH) receptor in human olfactory GnRH-secreting neurons: an autocrine GnRH loop underlies neuronal migration.
Olfactory neurons and gonadotropin-releasing hormone (GnRH) neurons share a common origin during organogenesis. Kallmann's syndrome, clinically characterized by anosmia and hypogonadotropic hypogonadism, is due to an abnormality in the migration of olfactory and GnRH neurons. We recently characterized the human FNC-B4 cell line, which retains properties present in vivo in both olfactory and GnRH neurons. In this study, we found that FNC-B4 neurons expressed GnRH receptor and responded to GnRH with time- and dose-dependent increases in GnRH gene expression and protein release (up to 5-fold). In addition, GnRH and its analogs stimulated cAMP production and calcium mobilization, although at different biological thresholds (nanomolar for cAMP and micromolar concentrations for calcium). We also observed that GnRH triggered axon growth, actin cytoskeleton remodeling, and a dose-dependent increase in migration (up to 3-4-fold), whereas it down-regulated nestin expression. All these effects were blocked by a specific GnRH receptor antagonist, cetrorelix. We suggest that GnRH, secreted by olfactory neuroblasts, acts in an autocrine pattern to promote differentiation and migration of those cells that diverge from the olfactory sensory lineage and are committed to becoming GnRH neurons.
Romanelli
Roberto Giulio
RG
Department of Internal Medicine, University of Florence, School of Medicine, Florence I-50134, Italy.
Barni
Tullio
T
Maggi
Mario
M
Luconi
Michaela
M
Failli
Paola
P
Pezzatini
Anna
A
Pelo
Elisabetta
E
Torricelli
Francesca
F
Crescioli
Clara
C
Ferruzzi
Pietro
P
Salerno
Roberto
R
Marini
Mirca
M
Rotella
Carlo Maria
CM
Vannelli
Gabriella B
GB
D001483:Base Sequence; D002064:Buserelin / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D000242:Cyclic AMP / Q000378:metabolism; D017931:DNA Primers; D005786:Gene Expression Regulation; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D018034:Olfactory Receptor Neurons / Q000187:drug effects / Q000502:physiology*; D037342:Pertussis Toxin / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011966:Receptors, LHRH / Q000737:chemistry / Q000235:genetics* / Q000502:physiology
D016895:Culture Media, Serum-Free; D017931:DNA Primers; D006727:Hormone Antagonists; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D000242:Cyclic AMP; D037342:Pertussis Toxin; C062876:cetrorelix; D002064:Buserelin