| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
EDITORIAL |
Prince Henry’s Institute of Medical Research, PO Box 5152, Clayton, Victoria 3168, Australia
Correspondence should be addressed to A Drummond; Email: ann.drummond{at}princehenrys.org
Transforming growth factor-ß (TGF-ß) is the index member of a large family of multifunctional growth factors. They were named originally for their ability to induce normal rat kidney fibroblasts to grow in soft agar in the presence of Epidermal Growth Factor (EGF) (De Larco & Todaro 1978, Roberts et al. 1981). There are 5 subtypes, all products of separate genes, three of which, TGF-ß1, ß2 and ß3, have been shown to be expressed in mammalian ovarian cells (Derynck et al. 1988, Hernandez et al. 1990, Mulheron & Schomberg 1990). These factors are synthesized in inactive precursor forms that undergo cleavage to produce monomers, which can dimerize to 25 kDa forms through the conserved cysteine regions. The active regions of the TGF-ß monomers share 98–100% identity.
The isolation and cloning of inhibin and erythroid differentiation factor (subsequently called activin), and Mullerian inhibiting substance (MIS) led to the observation that these peptides are also members of the TGF-ß superfamily. The family has grown to consist of more than 40 members (for a review see Chang et al. 2002), including the growth differentiation factors (GDFs) and bone morphogenetic proteins (BMPs) (Fig. 1
). Members of the family are related by sequence homology (30–40%) and conservation of the cysteine residues. Many also share a similar signal transduction mechanism involving serine–threonine kinase receptors with downstream Smad signalling pathways (for reviews see Miyazawa et al. 2002, Shi & Massague 2003, Lin et al. 2006).
|
In this issue of Reproduction, TGF-ß signalling in reproductive tissues is reviewed. This focus issue begins with a chapter on the signal transduction systems that underlie the actions of TGF-ß family members in reproductive tissues. As defined by its title, Lin et al.(2006) cover the structural basis of TGF-ß, BMP and activin ligand binding. A discussion of ligand-receptor interactions and the inhibition of TGF-ß superfamily signaling by extracellular antagonists (noggin, follistatin, chordin/SOG etc) or membrane bound inhibitors (BAMBI, betaglycan etc), are included.
Phil Knight and Claire Glister (2006) review the role that members of the TGF-ß superfamily play in ovarian follicle development, across a range of species. They address the contribution of the three major cell types of the follicle (oocytes, granulosa and theca cells) to the local milieu within the ovary, which might regulate the transition from primordial to antral follicles, selection of the dominant follicle and ovulation.
Bilezikjian et al.(2006) have reviewed the effects of the TGF-ß superfamily of ligands on the pituitary, with emphasis on the inhibin/activin/follistatin nexus and the regulation of gonadotrope function.
Jones et al.(2006) summarize the roles that TGF-ß superfamily members play in the uterus and placenta, with particular reference to the processes of endometrial cycling, menstruation, implantation and pregnancy.
Testicular development is addressed in a review by Itman et al.(2006). The roles that the TGF-ß superfamily members play in the specification of germ cells and their subsequent proliferation or death during embryonic development, in spermatogonial proliferation, differentiation and during adult spermatogenesis, are addressed.
Several outstanding issues arise from these reviews. They include:
The actions of the TGF-ß superfamily members in reproductive tissues represents a very complex set of interactions that are context and spatio-temporally specific, and will require much more research before we can fully understand and appreciate the diversity and necessity of their actions.
We would like to thank the authors for their contributions and the staff at Reproduction for inviting us to co-ordinate and edit this special issue of the journal.
References
Bilezikjian LM, Blount AL, Donaldson CJ & Vale WW 2006 Pituitary actions of ligands of the TGF-ß family: activins and inhibins. Reproduction 132 207–215.
Chang H, Brown CW & Matzuk MM 2002 Genetic analysis of the mammalian transforming growth factor-ß superfamily. Endocrine Reviews 23 787–823.
De Larco JE & Todaro GJ 1978 Growth factors from murine sarcoma virus-transformed cells. PNAS 75 4001–4005.
Derynck R, Lindquist PB, Lee A, Wen D, Tamm J, GRaycar JL, Rhee L, Mason AJ, Miller DA, Coffey RJ, Moses HL & Chen EY 1988 A new type of transforming growth factor-ß, TGF-ß3. EMBO Journal 7 3737–3743.[Web of Science][Medline]
Findlay JK & Risbridger GP 1987 Intragonadal control mechanisms. Bailliere’s Clinical Endocrinology and Metabolism 1 223–243.[CrossRef][Web of Science][Medline]
Hernandez ER, Hurwitz A, Payne DW, Dharmarajan AM, Purchio A & Adashi EY 1990 Transforming growth factor-ß1 inhibits ovarian androgen production: gene expression, cellular localisation, mechanism(s) and site(s) of action. Endocrinology 127 2804–2811.
Itman C, Mendis S, Barakat B & Loveland KL 2006 All in the family: TGF-ß family action in testis development. Reproduction 132 233–246.
Jones RL, Stoikos C, Findlay JK & Salamonsen LA 2006 TGF-ß superfamily expression and actions in the endometrium and placenta. Reproduction 132 217–232.
Knight PG & Glister C 2006 TGF-ß superfamily members and ovarian follicle development. Reproduction 132 191–206.
Lin SJ, Lerch TF, Cook RW, Jardetzky TS & Woodruff TK 2006 The structural basis of TGF-ß, bone morphogenic protein, and activin ligand binding. Reproduction 132 179–190.
Miyazawa K, Shinozaki M, Hara T, Furuya T & Miyazono K 2002 Two major Smad pathways in TGF-ß superfamily signaling. Genes to Cells 7 1191–1204.[Abstract]
Mulheron GW & Schomberg DW 1990 Rat granulosa cells express transforming growth factor-ß, type 2 messenger ribonucleic acid which is regulatable by follicle stimulating hormone in vitro. Endocrinology 126 1777–1779.
Roberts AB, Ananzo MA, Lamb LC, Smith JM & Sporn MB 1981 New class of transforming growth factors potentiated by epidermal growth factor: isolation from non-neoplastic tissues. PNAS 78 5339–5343.
Shi Y & Massague J 2003 Mechanisms of TGF-ß signalling from cell membrane to the nucleus. Cell 113 685–700.[CrossRef][Web of Science][Medline]
Sporn MB & Todaro GJ 1980 Autocrine secretion and malignant transformation of cells. New England Journal of Medicine 303 878–880.[Web of Science][Medline]
This article has been cited by other articles:
 |
|
 |
|
  R. Zachow and M. Uzumcu The hepatocyte growth factor system as a regulator of female and male gonadal function J. Endocrinol., December 1, 2007; 195(3): 359 - 371. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
