Rerouting of a follicle-stimulating hormone analog to the regulated secretory pathway

Christopher A. Pearl, Albina Jablonka-Shariff, Irving Boime

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

LH and FSH are produced by the same gonadotrope cells of the anterior pituitary but differ in their mode of secretion. This coordinated secretion of LH and FSH is essential for normal follicular development and ovulation in females and for spermatogenesis in males. The structural signals encoded in the LH and FSH subunits that govern the intracellular sorting of LH through the regulated secretory pathway and FSH through the constitutive pathway are largely unknown. Our laboratory recently identified the seven amino acid carboxy tail of LHβ as a sorting signal for LH in GH3 cells. Here we compared the morphological features of GH3 cells expressing an FSH analog containing the heptapeptide (FL7AA) with wild-type FSH using confocal microscopy. These experiments were performed to develop a rerouting model for examining structure-function links between secretion pathways of FSH/LH and their biological action. Both FSH- and LH-expressing cells exhibit a fluorescence pattern of randomly dispersed cytoplasmic puncta. FL7AA expressing cells have more intracellular accumulation compared with wild-type FSH and display a unique halo pattern of fluorescence near the plasma membrane. Such a pattern was not observed in cells expressing FSH or LH. Our results demonstrate that this FSH analog containing the carboxy heptapeptide of LHβis rerouted to the regulated secretory pathway in GH3 cells. This rerouted gonadotropin provides a unique model to study the trafficking, regulation, and function of LH and FSH.

Original languageEnglish
Pages (from-to)388-393
Number of pages6
JournalEndocrinology
Volume151
Issue number1
DOIs
StatePublished - Jan 2010

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