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Published on: April 7, 2023
Absence of the long noncoding RNA H19 results in aberrant ovarian STAR and progesterone production
Yong Chen1, Jing Wang2, Yanhong Fan3
1Department of Human Anatomy and Histology, and Embryology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian Province, 350122, PR China; Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA.
Abstract:
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.
Insights
Noncoding RNAs H19 and let-7 regulate steroid hormone production. Loss of H19 disrupts ovarian steroidogenic acute regulatory protein (STAR) and alters progesterone levels in mice.
Area of Science:
- Endocrinology
- Molecular Biology
- Reproductive Biology
Background:
- Steroidogenesis, crucial for reproduction, is regulated by the steroidogenic acute regulatory protein (STAR).
- STAR expression is tissue-specific and tightly controlled.
- Previous in vitro studies identified H19 and let-7 as posttranscriptional regulators of STAR.
Purpose of the Study:
- To investigate the in vivo function of H19 and let-7 in regulating STAR.
- To determine the role of cAMP in this regulatory pathway.
- To assess the impact of H19 loss on ovarian STAR and progesterone production.
Main Methods:
- Utilized an H19 knockout (H19KO) mouse model.
- Investigated STAR regulation in vivo.
- Measured progesterone levels.
Main Results:
- Demonstrated that H19-mediated regulation of STAR is functional in vivo and responsive to cAMP.
- Observed disrupted ovarian STAR expression in H19KO mice.
- Found altered progesterone production in H19KO mice.
Conclusions:
- Noncoding RNA H19 plays a significant role in regulating ovarian STAR expression and steroid hormone production in vivo.
- This regulatory mechanism, mediated by noncoding RNAs, is important for steroidogenesis.
- Further research into noncoding RNA regulation of STAR is warranted.
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