Lineage specification of ovarian theca cells requires multicellular interactions via oocyte and granulosa cells. Liu C et al. (2015) Organogenesis of the ovary is a highly orchestrated process involving multiple lineage determination of ovarian surface epithelium, granulosa cells and theca cells. Although the sources of ovarian surface epithelium and granulosa cells are known, the origin(s) of theca progenitor cells have not been definitively identified. Here we show that theca cells derive from two sources: Wt1(+) cells indigenous to the ovary and Gli1(+) mesenchymal cells that migrate from the mesonephros. These progenitors acquire theca lineage marker Gli1 in response to paracrine signals Desert hedgehog (Dhh) and Indian hedgehog (Ihh) from granulosa cells. Ovaries lacking Dhh/Ihh exhibit theca layer loss, blunted steroid production, arrested folliculogenesis and failure to form corpora lutea. Production of Dhh/Ihh in granulosa cells requires growth differentiation factor 9 (GDF9) from the oocyte. Our studies provide the first genetic evidence for the origins of theca cells and reveal a multicellular interaction critical for the formation of a functional theca./////////////////Where are the theca cells from: the mechanism of theca cells derivation and differentiation. Liu T et al. (2020) Mammalian follicles are composed of oocytes, granulosa cells, and theca cells. Theca cells form in the secondary follicles, maintaining follicular structural integrity and secreting steroid hormones. Two main sources of theca cells exist: Wilms tumor 1 positive (Wt1) cells native to the ovary and Gli1 mesenchymal cells migrated from the mesonephros. Normal folliculogenesis is a process where oocytes, granulosa cells, and theca cells constantly interact with and support each other through autocrine and paracrine mechanisms. The proliferation and differentiation of theca cells are regulated by oocyte-derived factors, including growth development factor 9 and bone morphogenetic protein 15, and granulosa cell-derived factors, including desert hedgehog, Indian hedgehog, kit ligand, insulin-like growth factor 1, as well as hormones such as insulin and growth hormones.. Current research on the origin of theca cells is limited. Identifying the origin of theca cells will help us to systematically elaborate the mechanisms of follicular formation and development.//////////////////
General function
Nucleic acid binding, DNA binding, Transcription factor
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Cellular localization
Nuclear
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Ovarian function
Primary follicle growth, Steroid metabolism
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The Hedgehog-Patched Signaling Pathway and Function in the Mammalian Ovary: A Novel Role for Hedgehog proteins in Stimulating Proliferation and Steroidogenesis of Theca cells. Spicer L et al. The expression of hedgehog (Hh) genes, their receptor, and the co-receptor in mice, rat and bovine ovaries were investigated. Reverse transcription-polymerase chain reaction (RT-PCR) of ovarian transcripts in mice showed amplification of transcripts for Indian (Ihh) and Desert (Dhh) hedgehog, Patched 1 (Ptch1), and Smoothened (Smo) genes. Semi-quantitative RT-PCR and Northern blot analyses showed that whole ovarian Ihh and Dhh transcripts were less 4-24 h after hCG versus 0-48 h after PMSG treatment in mice, whereas mouse Ptch1 and Smo transcripts were expressed throughout the gonadotropin treatments. Quantitative real-time RT-PCR (qRT-PCR) revealed the expression of the hedgehog-Patched signaling system with Ihh mRNA abundance in granulosa cells greater whereas Smo and Ptch1 mRNA abundance less in theca cells of small versus large follicles of cattle. In cultured rat and bovine theca-interstitial cells, qRT-PCR analyses revealed abundance of Gli1 and Ptch1 mRNAs were increased (P < 0.05) with SHH treatment. Additional studies using cultured bovine theca cells indicated that SHH induces proliferation and androstenedione production. IGF1 decreased Ihh mRNA abundance in bovine granulosa cells. The expression and regulation of Ihh transcripts in granulosa cells and Ptch1 mRNA in theca cells suggests a potential paracrine role of this system in bovine follicular development. These studies illustrate for the first time hedgehog activation of Gli1 transcriptional factor in theca cells and its stimulation of theca cell proliferation and androgen biosynthesis.
Expression regulated by
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Ovarian localization
Theca
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Wijgerde M, et al reported hedgehog signaling in mouse ovary: Ihh and Dhh from granulosa cells induce target gene expression in developing theca cells.
Follicle development in the mammalian ovary requires interactions between the oocyte, granulosa cells, and theca cells, co-ordinating gametogenesis and steroidogenesis. Here, we show that granulosa cells of growing follicles in mouse ovary act as a source of hedgehog signaling. Expression of indian hedgehog (Ihh) and desert hedgehog (Dhh) mRNAs initiates in granulosa cells at the primary follicle stage, and we find induced expression of the hedgehog target genes Ptch1 and Gli1, in the surrounding pre-theca cell compartment. Cyclopamine, a highly specific hedgehog signaling antagonist, inhibits this induced expression of target genes, in cultured neonatal mouse ovaries. The theca cell compartment remains a target of hedgehog signaling throughout follicle development, showing induced expression of the hedgehog target genes Ptch1, Ptch2, Hip1, and Gli1. In peri-ovulatory follicles, a dynamic synchrony between loss of hedgehog expression and loss of induced target gene expression is observed. Oocytes are unable to respond to hedgehog, since they lack expression of the essential signal transducer Smo (smoothened). The present results point to a prominent role of hedgehog signaling in the communication between granulosa cells and developing theca cells.