Transforming growth factor-beta inhibits the growth of multiple epithelial
cell types, and loss of this negative regulation is thought to contribute to tumor development.
The types I and II TGF-beta receptors (Lin et al., 1992)
belong to the serine-threonine kinase family. The many activities of TGF-beta in regulating cell proliferation and
differentiation and extracellular matrix production are mediated through these receptors. Type II receptors alone can bind ligand, but require association with type I receptors for activation of
their kinase (signaling) function.
Richards AJ, et al 1999 reported that activin and TGFbeta limit murine primordial germ cell
proliferation.
Mammalian primordial germ cells (PGCs) proliferate as they migrate from their
initial location in the extraembryonic mesoderm to the genital ridge, the gonadal
anlage. Once in the genital ridge, PGCs cease dividing and differentiate according
to their gender. Growth factor receptors encoded in RNA obtained from purified germ
cells were analyzed shortly after their arrival in the genital ridge. Receptors for two members of
the TGFbeta superfamily were found, TGFbeta1 and activin. As the signal-transducing domains of both receptor systems are highly conserved, the effects of both TGFbeta1 and activin on PGCs would be expected to be similar.
It was found that both ligands limited the accumulation of germ cells in primary PGC
cultures. BrdU incorporation assays demonstrated that either ligand inhibits PGC
proliferation. These results suggest that these signal transduction pathways are
important elements of the mechanism that determines germ cell endowment.
Expression regulated by
FSH, Growth Factors/ cytokines, mir145
Comment
Expression Patterns and Regulatory Functions of MicroRNAs During the Initiation of Primordial Follicle Development in the Neonatal Mouse Ovary. Yang S 2013 et al.
The initiation of primordial follicle development is essential for female fertility, but the signals that trigger this process are poorly understood. Given the potentially important roles of miRNAs in the ovary, we aimed to study the expression patterns and regulatory functions of miRNAs during the initiation of primordial follicle development. miRNA expression patterns in the neonatal mouse ovary were profiled by microarray, and 24 miRNAs whose abundances differed significantly between ovaries from 3- and 5-day-old mice were identified. Pathway enrichment analysis revealed that 48 signal transduction pathways are modulated by the up-regulated miRNAs and 29 pathways are modulated by the down-regulated miRNAs (P-value and false discovery rate (FDR) < 0.001). A miRNA-mRNA regulatory network was established for TGF-beta signaling pathway-related genes. Among the miRNAs involved in this pathway, miR-145 was chosen for further analysis. Down-regulation of miR-145 using an antagomir (AT) decreased the proportion and number of the primordial follicles and increased that of the growing follicles in the cultured ovaries (P < 0.05). The mean oocyte diameter in the primordial follicles was significantly greater in the AT group relative to the antagomir negative control (AN) group (P < 0.05), whereas the mean oocyte diameter in growing follicles was smaller in the AT group than in the AN group. In addition, we confirmed that miR-145 targets Tgfbr2. The miR-145 antagomir caused an increase in TGFBR2 expression and activation of Smad signaling but did not affect the p38 MAPK or JNK pathway. These data suggest that miRNAs and the signaling pathways they modulate are involved in the initiation of primordial follicle development. miR-145 targets Tgfbr2 to regulate the initiation of primordial follicle development and maintain primordial follicle quiescence.
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Roy SK, et al. $9570266] reported The expression patterns of transforming growth factor (TGF)-beta receptor type I (TbetaRI) and -II
(TbetaRII) in pre- and post-menopausal human ovaries, and the in-vitro effects of follicle stimulating
hormone (FSH), epidermal growth factor (EGF) and transforming growth factor-beta1 (TGF-beta1) on
receptor expression in preantral follicles were evaluated using immunohistochemistry and
immunoblotting. Both types of receptor were present in granulosa, theca and interstitial cells; however,
more mural than antral granulosa cells were TbetaRII positive. Preantral follicles in class 1 and 2 responded in vitro to FSH and EGF with increased growth and a
corresponding increase in TbetaRII expression in granulosa cells.
Ismail RS, et al. reported that transforming growth factor-beta regulates Kit ligand expression in rat ovarian surface epithelial
cells.
Follicle stages
Primordial, Primary, Secondary, Antral, Preovulatory, Corpus luteum
Comment
Schilling B, et al. reported the expression of transforming growth factor (TGF)-beta1, TGF-beta2, and TGF-beta3 and of type I
and II TGF-beta receptors during the development of the human fetal ovary.
During the first trimester, immunohistochemical analysis for TGF-beta1, TGF-beta2,
and TGF-beta receptor type I revealed homogeneous light staining of the ovary. Staining for TGF-beta3
and TGF-beta receptor type II was predominantly in the oocytes. During the second trimester, staining for
all three TGF-beta isoforms and both receptors was predominantly in the oocytes.
Immunohistochemistry was used by Qu JP et al
to study the expression of insulin-like growth factor (IGF) type I receptor
(IGF-IR) and transforming growth factor-beta (TGF beta) type I (TGF beta R-I)
and type II (T beta R-II) receptors in fresh and frozen ovarian tissues from
14 women. Immunoreactivities for IGF-IR and TGF beta R-I were present
simultaneously in the oocytes of primordial, pre-antral and antral follicles.
Staining for both IGF-IR and TGF beta R-I was also observed in granulosa cells
of primordial, pre-antral and antral follicles. IGF-IR and TGF beta R-I also
stained in thecal cells of pre-antral and antral follicles. Stromal cells in
surrounding ovarian tissue expressed IGF-IR and TGF beta R-I at various
follicular stages. Unlike TGF beta R-I, TGF beta R-II was expressed only in the
oocytes of primordial and primary follicles, and with weak staining intensity
in thecal cells. No significant staining for TGF beta R-II was found in oocytes
and granulosa cells of antral follicles.
Wehrenberg U, et al. reported possible involvement of transforming growth factor-beta 1 and transforming growth factor-beta
receptor type II during luteinization in the marmoset ovary.