TGF-B2 is one of four different isoforms related to TGF-B1. TGF-B 1-3 are found in mammalian tissues. TGF-B2 mRNA is expressed by rat (Mulheron and Schomberg, 1990) Mulheron et al. (1991) and human (Mulheron et al., 1992a) ovarian cells. The murine TGF-B2 nucleotide sequence was reported by Miller et al. (1989) . There is 70% amino acid sequence homology between TGF-B1 and TGF-B2.
General function
Ligand, Growth factor, Cell death/survival, Cell cycle regulation, DNA Replication
Comment
With few exceptions the action of TGF-B2 and TGF-B1 are indistiguishable. Differences in activity were reported in hematopoietic (Ohta et al., 1987) and embryonic (Rosa et al., 1988) systems. Modulation by TGF-B2 and TGF-B1 of granulosa cell (GC) FSH-dependent LH receptor (LHR) induction is equivalent. Importantly, however, the direction of this response is species-dependent (Gitay-Goren et al., 1993) .
Cellular localization
Extracellular Matrix, Secreted
Comment
A variant in the fibrillin-3 gene is associated with TGF-β and inhibin B levels in women with polycystic ovary syndrome. Raja-Khan N et al. (2010) In an attempt to evaluate the association between allele 8 (A8) of D19S884 in the fibrillin-3 gene and circulating transforming growth factor (TGF) β and inhibin levels in women with polycystic ovary syndrome (PCOS), we studied 120 similarly aged women from families with PCOS and compared 40 women with PCOS who did not have A8 (A8- PCOS) with 40 women with PCOS who had A8 (A8+ PCOS) and 40 normally menstruating women who did not have either PCOS or A8 (A8- Non-PCOS). A8- PCOS is associated with higher levels of TGF-β1 compared with A8+ PCOS or A8- Non-PCOS, similar levels of TGF-β2 compared with A8+ PCOS but lower levels of TGF-β2 compared with A8- Non-PCOS, and lower levels of inhibin B and aldosterone compared with A8+ PCOS.//////////////////
TGF-B1 (and presumably TGF-B2) is a general growth inhibitor. The response in GC is an exception to this. TGF-B1 combination with insulin-like growth factor-1 (IGF-1) and epidermal growth factor (EGF) form a functional mitogenic complex (May et al., 1988) .
In addition to the work mentioned above with isolated theca or GC, TGF-B2 mRNA is expressed by human cumulus cells (Mulheron et al., 1992a) .Transforming growth factor-beta isoform expression during bovine ovarian antral follicle development.
Nilsson EE, et al 2003 .
Transforming growth factor-beta (TGF-beta) isoforms are important paracrine and autocrine signaling molecules for the regulation of ovarian follicle growth and physiology. Effective communication between the epithelial granulosa cells, the mesenchymal theca cells, and the oocyte is vital for ovarian function and reproductive success. The expression, localization, and regulation of TGF-beta isoforms in the developing bovine follicle was examined using both immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (RT-PCR) procedures. TGF-beta1 protein was found to be present in the granulosa cells of early pre-antral, early antral, and 1-2 mm follicles. Interestingly, there was no visible staining of granulosa cells of 3-5 or 5-10 mm follicles. There was also no TGF-beta1 staining of theca cells. TGF-beta2 and TGF-beta3 staining were present in the granulosa and theca cells of all follicle stages examined. The levels of TGF-beta mRNA expression in granulosa and theca cells from antral follicles was measured using quantitative RT-PCR. For each isoform mRNA expression levels did not change in different sized antral follicles. TGF-beta3 mRNA levels were much higher than those of TGF-beta1 and TGF-beta2 in both granulosa and theca. Expression levels were higher in theca than in granulosa for TGF-beta2 and TGF-beta3. FSH was found to decrease TGF-beta1 mRNA expression in granulosa cells, but had no effect on TGF-beta2 and TGF-beta3. Bovine ovarian follicles were found to have a unique pattern of TGF-beta isoform expression and regulation when compared to other species (i.e., rodent, pig, quail, and human). The similarities and differences between the various species is discussed to help elucidate common functions of TGF-beta in the ovary. In summary, observations demonstrate that as antral follicles develop, TGF-beta3 is the most abundant TGF-beta isoform and TGF-beta1 protein levels decline in large follicles. Granulosa cell TGF-beta1 expression was decreased by FSH and this correlated with reduced levels in large antral follicles. TGF-betas involved in antral follicular growth and development appear to act as paracrine/autocrine signaling molecules having a species-specific pattern of expression.
Follicle stages
Secondary, Antral, Preovulatory
Comment
Using immunocytochemistry TGF-B2 has been localized in both preantral and antral hamster GC (Roy et al., 1992) .
Gueripel X, et al reported that sequential Gonadotropin Treatment of Immature Mice Leads to Amplification of Transforming Growth Factor {beta} Action, Via Upregulation of Receptor-Type 1, Smad 2 and 4, and Downregulation of Smad 6.
The present study was designed to establish the cellular localization and expression of transforming growth factor beta (TGFbeta) signaling pathway components, including TGFbeta1 and beta2; TGFbeta receptors type I (TbetaRI) and II (TbetaRII); and Smads 2, 3, 4, and 6 during gonadotropin-induced follicular maturation and ovulation in the mouse ovary. Immature 21-day-old mice were sequentially treated with recombinant human FSH, 5 IU daily for 3 days, and hCG once at Day 24 of life. Immunohistochemical experiments revealed a TGFbeta1 staining in granulosa cells (GC) and theca interna cells (TIC) as well as in oocytes, whereas that of TGFbeta2 was mainly localized in oocytes and GC. Strong immunostaining for both TbetaRI and -RII was observed in the TIC and, to a lesser extent, in GC. Whereas oocytes did not exhibit any staining for TbetaRII, their TbetaRI immunostaining was strong. Smads were detected in oocytes, GC, and luteal cells and in a lesser amount in TIC; the immunostaining for Smad 4 was the strongest. Western blotting and reverse transcription-polymerase chain reaction analyses indicated that, in response to gonadotropins, TGFbeta2, TbetaRI, Smad 2 and Smad 4 mRNA and protein levels increased, while those of Smad 6 decreased in ovarian homogenates. In conclusion, these results show that, in a model of immature mouse exposed to a sequential gonadotropin treatment, FSH and LH increased the expression of the TGFbeta signaling system through the increase of TGFbeta2, TbetaRI, stimulatory Smad 2, and common Smad 4 expression, which occurred concomitantly with a decrease of the inhibitory Smad 6 expression.