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Endocrine Abstracts (2019) 63 GP62 | DOI: 10.1530/endoabs.63.GP62

1Department of Cell Biology, Physiology and Immunology, University of Córdoba & Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC)/Hospital Universitario Reina Sofia, Córdoba, Spain; 2Department of Medicine, Faculty of Health Sciences, University of A Coruña, Instituto de Investigación Biomédica (INIBIC), University Hospital A Coruña, A Coruña, Spain; 3Division of Endocrinology, Diabetes and Hypertension, Brigham and Women‘s Hospital and Harvard Medical School, Boston, USA; 4Department of Physiology, Medical Sciences Building, University of Toronto, Toronto, Canada; 5Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, LIM 42, Hospital das Clínicas, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, Brazil.


Mkrn3, the maternally imprinted gene encoding the makorin RING-finger protein-3, has recently emerged as putative pubertal repressor, as evidenced by central precocity caused by MKRN3 mutations in humans; yet, the molecular underpinnings of this key regulatory action remain largely unexplored. We report herein that the microRNA, miR-30, with three binding sites in a highly conserved region of its 3’-untranslated region (UTR), operates as repressor of Mkrn3 to control pubertal onset. Hypothalamic miR-30b expression increased, while Mkrn3 mRNA and protein content decreased, during rat postnatal maturation. Neonatal estrogen exposure, causing pubertal alterations, enhanced hypothalamic Mkrn3 and suppressed miR-30b expression in female rats. Functional in vitro analyses demonstrated a strong repressive action of miR-30b on Mkrn3 3’-UTR. Moreover, central infusion during the juvenile period of target site blockers, tailored to prevent miR-30 binding to Mkrn3 3’-UTR, reversed the prepubertal down-regulation of hypothalamic Mkrn3 protein and delayed female puberty. Collectively, our data unveil a novel hypothalamic miRNA pathway, involving miR-30, with a prominent role in the control of puberty via Mkrn3 repression. These findings expand our current understanding of the molecular basis of puberty and its disease states.

Volume 63

21st European Congress of Endocrinology

Lyon, France
18 May 2019 - 21 May 2019

European Society of Endocrinology 

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