Phospholipase C-related but catalytically inactive proteins regulate ovarian follicle development

Miho Matsuda, Masato Hirata

Research output: Contribution to journalArticle

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Abstract

Phospholipase C-related but catalytically inactive proteins PRIP-1 and -2 are inositol-1,4,5-trisphosphate binding proteins that are encoded by independent genes. Ablation of the Prip genes in mice impairs female fertility, which is manifested by fewer pregnancies, a decreased number of pups, and the decreased and increased secretion of gonadal steroids and gonadotropins, respectively. We investigated the involvement of the PRIPs in fertility, focusing on the ovaries of Prip-1 and -2 double-knock-out (DKO) mice. Multiple cystic follicles were observed in DKO ovaries, and a superovulation assay showed a markedly decreased number of ovulated oocytes. Cumulusoocyte complexes showed normal expansion, and artificial gonadotropin stimulation regulated the ovulation-related genes in a normal fashion, suggesting that the ovulation itself was probably normal.Ahistological analysis showed atresia in fewer follicles of the DKO ovaries, particularly in the secondary follicle stages. The expression of luteinizing hormone receptor (LHR) was aberrantly higher in developing follicles, and the phosphorylation of extracellular signal-regulated protein kinase, a downstream target of LH-LHR signaling, was higher in DKO granulosa cells. This suggests that the up-regulation of LH-LHR signaling is the cause of impaired follicle development. The serum estradiol level was lower, but estradiol production was unchanged in theDKOovaries. These results suggest that PRIPs are positively involved in the development of follicles via their regulation of LH-LHR signaling and estradiol secretion. Female DKO mice had higher serum levels of insulin, testosterone, and uncarboxylated osteocalcin, which, together with reduced fertility, are reminiscent of polycystic ovary syndrome in humans.

Original languageEnglish
Pages (from-to)8369-8380
Number of pages12
JournalJournal of Biological Chemistry
Volume292
Issue number20
DOIs
Publication statusPublished - May 19 2017

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LH Receptors
Ovarian Follicle
Type C Phospholipases
Fertility
Ovary
Estradiol
Genes
Ovulation
Gonadotropins
Knockout Mice
Proteins
Superovulation
Phosphorylation
Inositol 1,4,5-Trisphosphate
Granulosa Cells
Polycystic Ovary Syndrome
Osteocalcin
Extracellular Signal-Regulated MAP Kinases
Ablation
Serum

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Phospholipase C-related but catalytically inactive proteins regulate ovarian follicle development. / Matsuda, Miho; Hirata, Masato.

In: Journal of Biological Chemistry, Vol. 292, No. 20, 19.05.2017, p. 8369-8380.

Research output: Contribution to journalArticle

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