MicroRNA-7a2 Regulates Prolactin in Developing Lactotrophs and Prolactinoma Cells

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 lact...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 2021-02, Vol.162 (2), p.1
Main Authors: LaPierre, Mary P, Godbersen, Svenja, Torres Esteban, Mònica, Schad, Anaïs Nura, Treier, Mathias, Ghoshdastider, Umesh, Stoffel, Markus
Format: Article
Language:English
Subjects:
Adenoma
Analysis
Animal models
Animals
Cell Line
Embryogenesis
Embryonic development
Embryonic growth stage
Endocrine disorders
Endocrinology
Estradiol - metabolism
Female
Fertility
Gene expression
Genes
Hyperprolactinemia
Lactation
Lactotrophs - physiology
Male
Mice
MicroRNA
MicroRNAs
MicroRNAs - physiology
miRNA
Physiological aspects
Pituitary
Pituitary gland
Pituitary Neoplasms - metabolism
Prolactin
Prolactin - metabolism
Prolactinoma - metabolism
Proto-Oncogene Proteins c-raf - metabolism
Sex Characteristics
Sex hormones
Tumors
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Summary: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 (miR-7) is the most highly expressed miRNA 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.
ISSN:0013-7227
1945-7170
DOI:10.1210/endocr/bqaa220