MicroRNA-7a2 Regulates Prolactin in Developing Lactotrophs and Prolactinoma Cells
| Autor: | Mònica Torres Esteban, Anaïs Nura Schad, Mathias Treier, Svenja Godbersen, Mary P LaPierre, Markus Stoffel, Umesh Ghoshdastider |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine endocrine system Pituitary gland medicine.medical_specialty Lactotrophs Cell Biology Cell Line Prolactin cell Mice 03 medical and health sciences microRNA-7a2 pituitary lactotroph prolactin development Raf1 0302 clinical medicine Endocrinology Internal medicine microRNA medicine Animals Lactation Endocrine system Pituitary Neoplasms Prolactinoma Research Articles Sex Characteristics Estradiol Embryogenesis medicine.disease Prolactin Proto-Oncogene Proteins c-raf MicroRNAs Fertility 030104 developmental biology medicine.anatomical_structure Female 030217 neurology & neurosurgery |
| Zdroj: | Endocrinology Endocrinology, 162 (2) |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/endocr/bqaa220 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|