Human GnRH-secreting cultured neurons express activin betaA subunit mRNA and secrete dimeric activin A

Florio, Pasquale; Vannelli, G. B.; Luisi, Stefano; Barni, Tullio; Zonefrati, Roberto; Falaschi, C.; Bifulco, Giuseppe; Genazzani, Ar

doi:10.1530/eje.0.1430133

Cited by 11 publications

(9 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Activin appears to be made by neurons (Florio et al, 2000;Bottner et al, 2006) and acts on neurons (this report), suggesting that injury may induce a paracrine signaling event. This report shows that 10 or 25 ng/mL activin retained cortical neurons in defined medium.…”

Section: Discussionmentioning

confidence: 72%

Activin is a Neuronal Survival Factor that is Rapidly Increased after Transient Cerebral Ischemia and Hypoxia in Mice

Mukerji

Katsman

Wilber

et al. 2006

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

One approach for developing targeted stroke therapies is to identify the neuronal protective and destructive signaling pathways and gene expression that follow ischemic insult. In some neural injury models, the transforming growth factor-beta family member activin can provide neuroprotective effects in vivo and promote neuronal survival. This study tests if activin supports cortical neurons after ischemic challenge in vitro and if signals after cerebral ischemia involve activin in vivo. In a defined cell culture model that uses hydrogen peroxide (H2O2)-free radical stress, activin addition maintained neuronal survival. H2O2 treatment increased activin mRNA twofold in surviving cortical neurons, and inhibition of activin with neutralizing antibodies caused neuronal death. These data identify activin gene changes as a rapid response to oxidative stress, and indicate that endogenous activin acts as a protective factor for cortical neurons in vitro. Similarly, after transient focal cerebral ischemia in adult mice, activin mRNA increased at 1 and 4 h ipsilateral to the infarct but returned to control values at 24 h after reperfusion. Intracellular activated smad signals were detected in neurons adjacent to the infarct. Activin was also increased after 2 h of 11% hypoxia. Activin mRNA increased at 1 h but not 4 or 24 h after hypoxia, similar to the time course of erythropoietin and vascular endothelial growth factor induction. These findings identify activin as an early-regulated gene response to transient ischemia and hypoxia, and its function in cortical neuron survival during oxidative challenge provides a basis to test activin as a potential therapeutic in stroke injury.

show abstract

Section: Discussionmentioning

confidence: 72%

Activin is a Neuronal Survival Factor that is Rapidly Increased after Transient Cerebral Ischemia and Hypoxia in Mice

Mukerji

Katsman

Wilber

et al. 2006

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…Thus, FNC-B4 cells, retaining properties of both olfactory and GnRH neurons, provided a human model system to study the role of GnRH on neuronal commitment. We demonstrated previously (22)(23)(24) that FNC-B4 cells release authentic GnRH in response to various stimuli. The present study showed that FNC-B4 cells expressed both gene and protein for GnRH-R and that its activation led to GnRH up-regulation at gene and protein levels.…”

Section: Discussionmentioning

confidence: 77%

“…Although the cells have the some properties as those of immature neurons, they can differentiate and express neuronal markers and olfactory genes, as well as neuroendocrine characteristics (21)(22)(23)(24). FNC-B4 cells, grown as a monolayer, are non-tumorigenic and have a normal human karyotype.…”

Section: Methodsmentioning

confidence: 99%

“…This adult-onset hypogonadotropic hypogonadism represents one of the few treatable forms of male infertility (15). Our contribution to clarify this complex biological problem has been to utilize the human GnRH-secreting neuronal cell line, FNC-B4 neurons (21)(22)(23)(24). These primary long term cell cultures have been established, cloned, and propagated in vitro from human fetal olfactory epithelium (21).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Expression and Function of Gonadotropin-releasing Hormone (GnRH) Receptor in Human Olfactory GnRH-secreting Neurons

Romanelli

Barni

Maggi

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

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 dosedependent 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.

show abstract

“…Both GnRH-positive perikarya and fibers have been found in close association with activin ␤ A subunit-immunoreactive fibers as well as follistatin-positive cell bodies [19,20]. Various in vitro studies have demonstrated the ability of activin to stimulate GnRH secretion [21][22][23][24]. Studies showing increases in hypothalamic GnRH mRNA expression, but not in testosterone secretion, following administration of activin-A to male rats [25] suggest that peripheral changes in activin may regulate FSH secretion by acting directly not only at the pituitary level but also at the hypothalamic level.…”

Section: Introductionmentioning

confidence: 99%

Neuroendocrine Control of Follicle-Stimulating Hormone (FSH) Secretion: II. Is Follistatin-Induced Suppression of FSH Secretion Mediated via Changes in Activin Availability and Does It Involve Changes in Gonadotropin-Releasing Hormone Secretion?1

Padmanabhan

Battaglia

Brown

et al. 2002

Biology of Reproduction

View full text Add to dashboard Cite

The objective of the present study was to determine to what extent activin participates in setting the level of FSH secretion and if this regulation includes mediation via changes in GnRH secretion. We administered follistatin, the high-affinity binding protein for activin, to five ovariectomized sheep; we reasoned that the resultant binding of follistatin to activin should lower activin bioavailability and FSH secretion. Hypophyseal portal and peripheral blood samples were collected simultaneously at 10-min intervals for 18 h to measure GnRH, LH, FSH, and both activin-free and total follistatin. Six hours into collection, each ewe received 150 microg/kg i.v. of recombinant human follistatin-288. A week later, the same ewes were subjected to a second series of blood collections of similar length (time control). The FSH levels in pituitary portal blood were approximately 8-fold higher than those in the peripheral circulation. The FSH secretory patterns changed minimally during the time-control period. In contrast, follistatin had profound suppressive effects on FSH secretion. Maximal FSH suppression after FS-288 administration occurred at 5-6 h in the pituitary portal (65% suppression) and 9-10 h in the peripheral (48% suppression) circulation. Follistatin had no effect on GnRH or LH secretory patterns. Disappearance of total follistatin (i.e., free follistatin plus activin-bound follistatin) from the circulation was slower (P < 0.05) than that of free follistatin alone, suggesting that some of the follistatin was complexed with circulating activin, thus reducing the bioavailability of activin. The slower clearance of total follistatin and the lack of follistatin effects on GnRH secretion suggest that changes in activin bioavailability dictate the level of pituitary FSH secretion and that this is a pituitary-specific effect.

show abstract

Human GnRH-secreting cultured neurons express activin betaA subunit mRNA and secrete dimeric activin A

Cited by 11 publications

References 32 publications

Activin is a Neuronal Survival Factor that is Rapidly Increased after Transient Cerebral Ischemia and Hypoxia in Mice

Activin is a Neuronal Survival Factor that is Rapidly Increased after Transient Cerebral Ischemia and Hypoxia in Mice

Expression and Function of Gonadotropin-releasing Hormone (GnRH) Receptor in Human Olfactory GnRH-secreting Neurons

Neuroendocrine Control of Follicle-Stimulating Hormone (FSH) Secretion: II. Is Follistatin-Induced Suppression of FSH Secretion Mediated via Changes in Activin Availability and Does It Involve Changes in Gonadotropin-Releasing Hormone Secretion?1

Contact Info

Product

Resources

About