4.5 Article

Absence of the long noncoding RNA H19 results in aberrant ovarian STAR and progesterone production

Journal

MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 490, Issue -, Pages 15-20

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2019.03.009

Keywords

StAR; H19; let-7; Steroidogenesis; Progesterone; Long noncoding RNA; lncRNA; cAMP

Funding

  1. Reproductive Scientist Development Program (NIH-NICHD Project) [2K12HD000849-26]
  2. American Society for Reproductive Medicine
  3. NIH Loan Repayment Program
  4. Milstein Medical Asian American partnership Foundation (MMAAPF)

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The steroidogenic acute regulatory protein (STAR) governs the rate-limiting step in steroidogenesis, and its expression varies depending on the needs of the specific tissue. It is well known that tight control of steroid production is essential for multiple processes involved in reproduction. We recently showed that Star is regulated at the posttranscriptional level in vitro by H19 and let-7. Here we demonstrate that this novel regulatory mechanism is functional in vivo, regulated by cAMP, and that loss of H19 not only disrupts ovarian STAR but also results in altered progesterone production in an H19KO mouse model. This work further strengthens the possibility that noncoding-RNA-mediated regulation of STAR may play an important role in the regulation of steroid hormone production, and contributes further to our understanding of the many ways in which this important gene is regulated.

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