INVESTIGADORES
SOMOZA Gustavo Manuel
artículos
Título:
The Secretogranin II-derived Peptide Secretoneurin Stimulates Luteinizing Hormone Secretion from Gonadotrophs
Autor/es:
ZHAO, E.; BASAK, A.; WONG, ALEXANDER; KO, W.; CHEN, A.; LÓPEZ, GABRIELA C.; GREY, C.L.; CANOSA, LUIS FABIAN; SOMOZA, GUSTAVO M.; CHANG, JOHN P.; TRUDEAU, VANCE
Revista:
ENDOCRINOLOGY
Editorial:
The Endocrine Society
Referencias:
Año: 2009 vol. 150 p. 2273 - 2282
ISSN:
0013-7227
Resumen:
Secretoneurin (SN) is a 33-34 amino acid neuropeptide derived from secretogranin-II, a member of the chromogranin family. We previously synthesized a putative goldfish (gf) SN and demonstrated its ability to stimulate luteinizing hormone (LH) release in vivo. However, it was not known if goldfish actually produced the free SN peptide or if SN directly stimulates LH release from isolated pituitary cells. Using a combination of reverse phase-HPLC and mass spectrometry analysis, we isolated for the first time a 34 amino acid free gfSN peptide from the whole brain. Moreover, western blot analysis indicated the existence of this peptide in goldfish pituitary. Immunocytochemical localization studies revealed the presence of SN-immunoreactivity in prolactin cells of rostral pars distalis of the anterior pituitary. Additionally, we found that magnocellular cells of the goldfish preoptic region are highly immunoreactive for SN. These neurons send heavily labeled projections that pass through the pituitary stalk and innervate the neurointermediate and anterior lobes. In static 12-hr incubation of dispersed pituitary cells, application of SN antiserum reduced LH levels; whereas, 1 and 10 nM gfSN respectively induced 2.5-fold (p<0.001) and 1.9-fold (p<0.01) increments of LH release into the medium, increases similar to those elicited by 100 nM concentrations of gonadotropin-releasing hormone (GnRH). Like GnRH, gfSN elevated intracellular Ca2+ in identified gonadotrophs. While we do not yet know the relative contribution of neural SN or pituitary SN to LH release, we propose that SN could act as a neuroendocrine and/or paracrine factor to regulate LH release from the anterior pituitary.in vivo. However, it was not known if goldfish actually produced the free SN peptide or if SN directly stimulates LH release from isolated pituitary cells. Using a combination of reverse phase-HPLC and mass spectrometry analysis, we isolated for the first time a 34 amino acid free gfSN peptide from the whole brain. Moreover, western blot analysis indicated the existence of this peptide in goldfish pituitary. Immunocytochemical localization studies revealed the presence of SN-immunoreactivity in prolactin cells of rostral pars distalis of the anterior pituitary. Additionally, we found that magnocellular cells of the goldfish preoptic region are highly immunoreactive for SN. These neurons send heavily labeled projections that pass through the pituitary stalk and innervate the neurointermediate and anterior lobes. In static 12-hr incubation of dispersed pituitary cells, application of SN antiserum reduced LH levels; whereas, 1 and 10 nM gfSN respectively induced 2.5-fold (p<0.001) and 1.9-fold (p<0.01) increments of LH release into the medium, increases similar to those elicited by 100 nM concentrations of gonadotropin-releasing hormone (GnRH). Like GnRH, gfSN elevated intracellular Ca2+ in identified gonadotrophs. While we do not yet know the relative contribution of neural SN or pituitary SN to LH release, we propose that SN could act as a neuroendocrine and/or paracrine factor to regulate LH release from the anterior pituitary.