Transforming growth factors (TGFs) are biologically active polypeptides that reversibly confer the transformed
phenotype on cultured cells. Alpha-TGF shows about 40% sequence homology with epidermal growth factor (EGF) and competes with EGF for binding to the EGF receptor, stimulating its phosphorylation and
producing a mitogenic response.
NCBI Summary:
Transforming growth factors (TGFs) are biologically active polypeptides that reversibly confer the transformed phenotype on cultured cells. Alpha-TGF shows about 40% sequence homology with epidermal growth factor (EGF; MIM 131530) and competes with EGF for binding to the EGF receptor (MIM 131550), stimulating its phosphorylation and producing a mitogenic response.[supplied by OMIM]
Skinner MK, et al. reported the regulation of ovarian cell growth through the local production of transforming growth factor-alpha
by theca cells.
Zhang ZW, et al. reported direct inhibition of rat granulosa cell inhibin production by epidermal growth factor in vitro. Hill JL et al examined the effects of EGF on Ca2+
mobilization as measured by its efflux from mouse oocytes at three time periods throughout maturation
(0-4 hr, 4-8 hr, and 12 hr). Immature cumulus oocyte complexes (COCs) removed from the ovary for less
than 4 hr exhibit oscillations in Ca2+ efflux that initiated 5-30 min following EGF stimulation. This
response was not observed in COCs matured for 4-8 hr or 12 hr or in unstimulated 0-4 hr COCs.
Denuded oocytes and cumulus cells did not show the same response to EGF (8.2 nM and 16.4 nM).
Immunohistochemistry for detection of the EGF receptor along with EGF internalization studies showed that receptors are present both on cumulus cells and the oocyte but EGF appears to be internalized mainly by the cumulus cells.
Expression regulated by
LH
Comment
Ovarian localization
Oocyte, Granulosa, Theca
Comment
Scurry JP et al reported immunoreactivity of antibodies to epidermal growth factor,
transforming growth factors alpha, and epidermal
growth factor receptor in the premenopausal ovary.
The growth factor
antibodies reacted with theca, but not granulosa cells, whilst the antibody to EGFR reacted with both
types of follicular cells and was weakly reactive in ovarian stroma.
Skinner MK, et al. reported that thecal/interstitial cells produce an epidermal growth factor-like substance.
Tamura M et al reported the localization of mRNA for TGF alpha and EGF
was also studied by in-situ hybridization. Immunoreactive TGF alpha was observed predominantly in
theca cells in 12 of 33 antral follicles in the follicular phase but not in any of the 18 follicles in the luteal phase or in primordial and pre-antral
follicles. TGF alpha immunoreactivity was present predominantly in the luteinized granulosa cells in 13
of 15 corpora lutea in the luteal phase, which are considered to be active in steroidogenesis, but not in
any of the regressed corpora lutea. Accumulation of TGF alpha mRNA hybridization signal was
observed only in the theca cells in the follicles and luteinized theca cells in the ovaries that were
immunohistochemically positive for TGF alpha. Li S,1994 reported that In primordial follicles, only the oocyte showed intense immunostaining for TGF alpha, whereas the flattened pregranulosa cells were negative for the immunostaining. The earliest stage of follicular growth at which immunostaining for TGF alpha in granulosa cells and theca interna cells became apparent was the preantral stage. With the increase in the size of follicles, the intensity of TGF alpha immunostaining in the oocyte decreased, whereas the staining intensity of the granulosa and theca cells increased. The immunostaining for TGF alpha in granulosa and theca interna cells persisted in the corpus luteum, and further intensified during the midluteal phase. In the regressing corpus luteum, the immunostaining was present only in the peripheral theca lutein cells adjacent to the central scar tissue.
Bennett RA et al reported immunohistochemical localization of transforming growth
factor-alpha, epidermal growth factor (EGF), and EGF receptor
in the human fetal ovary.
Follicle stages
Antral, Preovulatory
Comment
Maruo T et al reported the expression of epidermal growth factor and its receptor in the
human ovary during follicular growth and regression.
In the preantral follicle stage, immunostaining for EGF and EGF receptor was observed only in
the oocyte. The staining intensity of the oocyte increased as the oocyte reached the preovulatory stage. In the antral follicle stage, immunostaining for EGF and EGF receptor became apparent in the granulosa and
theca interna cell layers, without appreciable staining in the surrounding stromal cells. The
immunostaining for EGF and EGF receptor in the granulosa cells and theca interna cells persisted in
preovulatory follicles and corpus luteum, and intensified in the midluteal phase. The results
obtained support EGF participation in oocyte maturation and in follicular growth and atresia. The intense immunostaining for EGF and EGF receptor observed in the theca interna cells in atretic follicles and the stromal cells surrounding corpus albicans in the cortex region raises the possibility of EGF involvement in transformation of thecal cells into stromal cells. Furthermore, the cell type-specific simultaneous
expression of EGF and EGF receptor in follicular and stromal compartments in the various stages of
follicular development suggests that an autocrine mode of EGF action may exist to regulate follicular
growth and regression in the human ovary.