Star and LH are required for normal ovarian steroidogenesis and oocyte maturation in zebrafish

Shang, G., Peng, X., Ji, C., Zhai, G., Ruan, Y., Lou, Q., Jin, X., He, J., Wang, H., Yin, Z.
Biology of reproduction   101(4): 760-770 (Journal)
Registered Authors
He, Jiangyan, Ji, Cheng, Wang, Han, Yin, Zhan, Zhai, Gang
knockout, lhb, oocyte maturation, star, zebrafish
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Female
  • Gene Knockdown Techniques
  • Gonadal Steroid Hormones/biosynthesis*
  • Gonadal Steroid Hormones/pharmacology
  • Luteinizing Hormone/genetics
  • Luteinizing Hormone/physiology*
  • Luteinizing Hormone, beta Subunit/genetics
  • Luteinizing Hormone, beta Subunit/physiology
  • Oocytes/drug effects
  • Oocytes/physiology
  • Oogenesis/drug effects
  • Oogenesis/genetics*
  • Ovary/drug effects
  • Ovary/metabolism*
  • Phosphoproteins/genetics
  • Phosphoproteins/physiology*
  • Transcription Activator-Like Effector Nucleases/genetics
  • Transcription Activator-Like Effector Nucleases/metabolism
  • Zebrafish/genetics
  • Zebrafish/physiology
31322169 Full text @ Biol. Reprod.
In recent studies, luteinizing hormone (LH) was reported to play important roles in oocyte maturation. However, the mechanism by which LH signaling, especially regarding the steroidogenesis process, affects oocyte maturation has not been clarified. In this study, zebrafish models with a functional deficiency in luteinizing hormone beta (Lhb) or steroidogenic acute regulatory protein (Star), an enzyme that promotes the transport of cholesterol into the inner mitochondrial membrane for maturation-induced hormone (MIH) production, were generated using transcription activator-like effector nucleases (TALENs). Similar phenotypes of the maturation-arrested oocytes in both female mutants have been observed. The levels of MIH in the oocytes of the female mutants were clearly decreased in both the lhb and star knockout zebrafish. The expression of star was dramatically down-regulated in the lhb mutant follicles and was clearly promoted by forskolin and hCG in vitro. Furthermore, treatment with the MIH precursors, pregnenolone or progesterone, as well as with MIH itself rescued the maturation-arrested oocyte phenotypes in both lhb and star mutants. The plasma levels of other steroids, including testosterone, estradiol, and cortisol, were not affected in the lhb mutants, while the levels of gonad hormones testosterone and estradiol were significantly increased in the star mutants. The cortisol levels were decreased in the star mutants. Collectively, our results confirm that LH plays important roles in the initiation of MIH synthesis from cholesterol and maintains oocyte maturation in zebrafish, as well as provide evidence that Star might act downstream of LH signaling in steroidogenesis.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes