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Chorionic gonadotropin and its receptor are both expressed in human retina, possible implications in normal and pathological conditions.

Dukic-Stefanovic S, Walther J, Wosch S, Zimmermann G, Wiedemann P, Alexander H, Claudepierre T - PLoS ONE (2012)

Bottom Line: Here we demonstrated that human retina is producing this gonadotropin that acts as a neuroactive molecule.Müller glial and retinal pigmented epithelial (RPE) cells are producing hCG that may affects neighbour cells expressing its receptor, namely cone photoreceptors.The exact physiological functions of this circuit have still to be identified, but the proliferation of photoreceptor-derived tumor induced by hCG demonstrated the need to control this neuroendocrine loop.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Faculty of Medicine, University of Leipzig, Leipzig, Germany.

ABSTRACT
Extra-gonadal role of gonadotropins has been re-evaluated over the last 20 years. In addition to pituitary secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH), the CNS has been clearly identified as a source of hCG acting locally to influence behaviour. Here we demonstrated that human retina is producing this gonadotropin that acts as a neuroactive molecule. Müller glial and retinal pigmented epithelial (RPE) cells are producing hCG that may affects neighbour cells expressing its receptor, namely cone photoreceptors. It was previously described that amacrine and retinal ganglion (RGC) cells are targets of the gonadotropin releasing hormone that control the secretion of all gonadotropins. Therefore our findings suggest that a complex neuroendocrine circuit exists in the retina, involving hCG secreting cells (glial and RPE), hCG targets (photoreceptors) and hCG-release controlling cells (amacrine and RGC). The exact physiological functions of this circuit have still to be identified, but the proliferation of photoreceptor-derived tumor induced by hCG demonstrated the need to control this neuroendocrine loop.

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hCG treatment induces retinoblastoma proliferation.Y79 retinoblastoma cells were treated with increasing concentration of hCG (0,001 to 100 IU/ml) for 60, 120 and 240 hours (light, middle and deep blue bars). Using wst-1 test, we measured increase of proliferation in retinoblastoma treated with hCG by calculating the absorbance ratio of treated vs untreated cells at these 3 time points. In addition, blocking antibody raised against a signaling extracellular domain of LHR was added during the same period (light and deep purple bars). We observed that hCG treatment at all concentrations, but 100 IU/ml, induced a relative increase in proliferation after 60 and 120 hours. This increase reached significance after 60 h (light blue bars) only for the 10 IU/ml condition. After 120 h (middle blue), all concentrations, except the highest, significantly increased the retinoblastoma cell proliferation. After 240 h (deep blue bars), no significant effect of hCG was observed. LHR antibody inhibits this effect for all concentrations tested after 60 (light purple bars) and 120 hours (deep purple bars).
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pone-0052567-g006: hCG treatment induces retinoblastoma proliferation.Y79 retinoblastoma cells were treated with increasing concentration of hCG (0,001 to 100 IU/ml) for 60, 120 and 240 hours (light, middle and deep blue bars). Using wst-1 test, we measured increase of proliferation in retinoblastoma treated with hCG by calculating the absorbance ratio of treated vs untreated cells at these 3 time points. In addition, blocking antibody raised against a signaling extracellular domain of LHR was added during the same period (light and deep purple bars). We observed that hCG treatment at all concentrations, but 100 IU/ml, induced a relative increase in proliferation after 60 and 120 hours. This increase reached significance after 60 h (light blue bars) only for the 10 IU/ml condition. After 120 h (middle blue), all concentrations, except the highest, significantly increased the retinoblastoma cell proliferation. After 240 h (deep blue bars), no significant effect of hCG was observed. LHR antibody inhibits this effect for all concentrations tested after 60 (light purple bars) and 120 hours (deep purple bars).

Mentions: When treated with hCG, Y79 showed an increased proliferation as revealed by wst1 assay (Figure 6). After 60 hours of treatment (light blue bars), the effect was statistically significant with 10 mU/ml of hCG only, while after 120 hours (middle blue bars), the proliferation was significantly increased with hCG concentration ranging from 0,1 mIU/ml to 10 IU/ml. After 240 hours hCG treatment had no statistical effect on retinoblastoma proliferation as values were comparable to the control situation (deep blue bars). This might be due to the half-life of the hormone and/or its dissociation into individual α and β chains that are known to exert opposite biologic activity [29]. Interestingly, treatment with 100 IU/ml of hCG did not stimulate retinoblastoma cell proliferation. With this concentration, wst1 values at all three time points were comparable to the control situation as absorbance ratio was close to 1 (horizontal dashed line). The specificity of the hCG effect on retinoblastoma cell proliferation was confirmed by the co-treatment with 2 ng/ml anti-LHR antibody raised against an extracellular domain of human LHR involved in signalization. Using anti-LHR, the proliferation induced by hCG was completely abolished and values were similar to the untreated Y79 cells after 60 (light purple bars) and 120 hours of co-treatments (deep purple bars), while another antibody, raised against beta-clusterin, did not compromised the effect of hCG treatment (data not shown).


Chorionic gonadotropin and its receptor are both expressed in human retina, possible implications in normal and pathological conditions.

Dukic-Stefanovic S, Walther J, Wosch S, Zimmermann G, Wiedemann P, Alexander H, Claudepierre T - PLoS ONE (2012)

hCG treatment induces retinoblastoma proliferation.Y79 retinoblastoma cells were treated with increasing concentration of hCG (0,001 to 100 IU/ml) for 60, 120 and 240 hours (light, middle and deep blue bars). Using wst-1 test, we measured increase of proliferation in retinoblastoma treated with hCG by calculating the absorbance ratio of treated vs untreated cells at these 3 time points. In addition, blocking antibody raised against a signaling extracellular domain of LHR was added during the same period (light and deep purple bars). We observed that hCG treatment at all concentrations, but 100 IU/ml, induced a relative increase in proliferation after 60 and 120 hours. This increase reached significance after 60 h (light blue bars) only for the 10 IU/ml condition. After 120 h (middle blue), all concentrations, except the highest, significantly increased the retinoblastoma cell proliferation. After 240 h (deep blue bars), no significant effect of hCG was observed. LHR antibody inhibits this effect for all concentrations tested after 60 (light purple bars) and 120 hours (deep purple bars).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3526580&req=5

pone-0052567-g006: hCG treatment induces retinoblastoma proliferation.Y79 retinoblastoma cells were treated with increasing concentration of hCG (0,001 to 100 IU/ml) for 60, 120 and 240 hours (light, middle and deep blue bars). Using wst-1 test, we measured increase of proliferation in retinoblastoma treated with hCG by calculating the absorbance ratio of treated vs untreated cells at these 3 time points. In addition, blocking antibody raised against a signaling extracellular domain of LHR was added during the same period (light and deep purple bars). We observed that hCG treatment at all concentrations, but 100 IU/ml, induced a relative increase in proliferation after 60 and 120 hours. This increase reached significance after 60 h (light blue bars) only for the 10 IU/ml condition. After 120 h (middle blue), all concentrations, except the highest, significantly increased the retinoblastoma cell proliferation. After 240 h (deep blue bars), no significant effect of hCG was observed. LHR antibody inhibits this effect for all concentrations tested after 60 (light purple bars) and 120 hours (deep purple bars).
Mentions: When treated with hCG, Y79 showed an increased proliferation as revealed by wst1 assay (Figure 6). After 60 hours of treatment (light blue bars), the effect was statistically significant with 10 mU/ml of hCG only, while after 120 hours (middle blue bars), the proliferation was significantly increased with hCG concentration ranging from 0,1 mIU/ml to 10 IU/ml. After 240 hours hCG treatment had no statistical effect on retinoblastoma proliferation as values were comparable to the control situation (deep blue bars). This might be due to the half-life of the hormone and/or its dissociation into individual α and β chains that are known to exert opposite biologic activity [29]. Interestingly, treatment with 100 IU/ml of hCG did not stimulate retinoblastoma cell proliferation. With this concentration, wst1 values at all three time points were comparable to the control situation as absorbance ratio was close to 1 (horizontal dashed line). The specificity of the hCG effect on retinoblastoma cell proliferation was confirmed by the co-treatment with 2 ng/ml anti-LHR antibody raised against an extracellular domain of human LHR involved in signalization. Using anti-LHR, the proliferation induced by hCG was completely abolished and values were similar to the untreated Y79 cells after 60 (light purple bars) and 120 hours of co-treatments (deep purple bars), while another antibody, raised against beta-clusterin, did not compromised the effect of hCG treatment (data not shown).

Bottom Line: Here we demonstrated that human retina is producing this gonadotropin that acts as a neuroactive molecule.Müller glial and retinal pigmented epithelial (RPE) cells are producing hCG that may affects neighbour cells expressing its receptor, namely cone photoreceptors.The exact physiological functions of this circuit have still to be identified, but the proliferation of photoreceptor-derived tumor induced by hCG demonstrated the need to control this neuroendocrine loop.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Faculty of Medicine, University of Leipzig, Leipzig, Germany.

ABSTRACT
Extra-gonadal role of gonadotropins has been re-evaluated over the last 20 years. In addition to pituitary secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH), the CNS has been clearly identified as a source of hCG acting locally to influence behaviour. Here we demonstrated that human retina is producing this gonadotropin that acts as a neuroactive molecule. Müller glial and retinal pigmented epithelial (RPE) cells are producing hCG that may affects neighbour cells expressing its receptor, namely cone photoreceptors. It was previously described that amacrine and retinal ganglion (RGC) cells are targets of the gonadotropin releasing hormone that control the secretion of all gonadotropins. Therefore our findings suggest that a complex neuroendocrine circuit exists in the retina, involving hCG secreting cells (glial and RPE), hCG targets (photoreceptors) and hCG-release controlling cells (amacrine and RGC). The exact physiological functions of this circuit have still to be identified, but the proliferation of photoreceptor-derived tumor induced by hCG demonstrated the need to control this neuroendocrine loop.

Show MeSH
Related in: MedlinePlus