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Pituitary somatotroph adenoma-derived exosomes: Characterization of nonhormonal actions

Journal of Clinical Endocrinology and Metabolism Sep 06, 2021

Zhou C, Shen S, Moran R, et al. - The findings shed light on the biological functions of somatotroph-derived exosomes and point to exosomes as non-hormonal pituitary-derived messengers.

  • Nanoparticle Tracking Analysis (NTA) was used to examine isolated extracellular vesicles (EVs), and Western blot was used to detect expressed exosomal markers, with non-pituitary fibroblast FR and myoblast H9C2 cells serving as controls.

  • NTA, exosomal marker detection, and GW4869 all reduced EV release, confirming pituitary EVs' exosomal identity.

  • Exosome secretion was increased in GH1 and GH3 cells by hydrocortisone, indicating a stress-related response.

  • Exosomal RNA profiles were distinct for pituitary cells, and rat primary hepatocytes exposed to GH1-exo displayed transcriptomic alterations distinct from those elicited by GH or PRL.

  • Intravenous GH1-exo injection to rats reduced hepatic Eif2ak2 and Atf4 mRNA expression, which are both involved in cAMP responses and amino acid biosynthesis.

  • In hepatocytes, GH1-exo suppressed protein synthesis and forskolin-induced cAMP levels.

  • In nude mice with splenic HCT116 implants, GH1-exo treated HCT116 cells showed dysregulated p53 and MAPK pathways, attenuated motility of malignant HCT116 cells, and decreased tumor metastases.

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