Helmholtz Gemeinschaft


MicroRNA-7a2 regulates prolactin in developing lactotrophs and prolactinoma cells

Item Type:Article
Title:MicroRNA-7a2 regulates prolactin in developing lactotrophs and prolactinoma cells
Creators Name:LaPierre, M.P. and Godbersen, S. and Esteban, M.T. and Schad, A.N. and Treier, M. and Ghoshdastider, U. and Stoffel, M.
Abstract:Prolactin production is controlled by a complex and temporally dynamic network of factors. Despite this tightly coordinated system, pathological hyperprolactinemia is a common endocrine disorder that is often not understood; thereby highlighting the need to expand our molecular understanding of lactotroph cell regulation. MicroRNA-7 is the most highly expressed microRNA family in the pituitary gland and the loss of the miR-7 family member, miR-7a2, is sufficient to reduce prolactin gene expression in mice. Here, we used conditional loss-of-function and gain-of-function mouse models to characterize the function of miR-7a2 in lactotroph cells. We found that pituitary miR-7a2 expression undergoes developmental and sex hormone-dependent regulation. Unexpectedly, the loss of mir-7a2 induces a premature increase in prolactin expression and lactotroph abundance during embryonic development, followed by a gradual loss of prolactin into adulthood. On the other hand, lactotroph development is delayed in mice overexpressing miR-7a2. This regulation of lactotroph function by miR-7a2 involves complementary mechanisms in multiple cell populations. In mouse pituitary and rat prolactinoma cells, miR-7a2 represses its target Raf1, which promotes prolactin gene expression. These findings shed light on the complex regulation of prolactin production and may have implications for the physiological and pathological mechanisms underlying hyperprolactinemia.
Keywords:MicroRNA-7a2, Pituitary, Lactotroph, Prolactin, Development, Raf1, Animals, Mice
Publisher:Oxford University Press
Page Range:bqaa220
Date:February 2021
Additional Information:Copyright © The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
Official Publication:https://doi.org/10.1210/endocr/bqaa220
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library