Seminiferous growth factor (SGF) is a novel mitogenic protein ubiquitous to the testes of mammals. The activity has been purified greater than or equal to 80,000-fold from bovine calf testes. SGF stimulates DNA synthesis in rat prospermatogonia and Sertoli cells at half-maximal effective concentrations (EC(50)) of less than or equal to 30 and 75 pM, respectively. The effect of SGF on prospermatogonia is down-regulated by TGF-beta1 or inhibin. SGF is mitogenic for mouse- derived TM(4) Sertoli cells (EC(50): 60 pM), TM(3) Leydig cells (EC(50):120 pM) and Balb/c 3T3 fibroblasts (EC(50): 300 pM) cells. SGF induces synthesis and secretion of specific proteins by TM(3) Leydig and TM(4) Sertoli cells, and is not recognized by antibodies to aFGF or bFGF. The peptide's physiochemical properties, and its ability to bind heparin, suggest it is a novel member of the FGF family. Research on SGF will involve: 1) sequencing of overlapping cDNAs cloned from mouse and/or bovine testicular directional cDNA expression libraries, by screening with degenerate oligonucleotide and/or antibody probes based on SGF's N-terminal and internal peptide sequences; 2) determining the pattern of SGF mRNA expression, relative abundance and cellular localization, during development and in the cycle of the seminiferous epithelium in adult mice. This will be undertaken by applying a combination of Northern analyses, polymerase chain reaction and in situ hybridization; 3) generating recombinant protein by inserting full length or truncated sequences of SGF into pET or pGEX vectors and preparing specific, high affinity antibodies against peptide-specific sequences; 4) defining the peptide's distribution in developing and adult gonads, with an emphasis on spermatogonia and Sertoli cells; 5) determining whether SGF stimulates germ cell DNA synthesis by acting directly on spermatogonia or indirectly on Sertoli cells, through interactions with specific surface receptors; and 6) characterizing SGF's surface receptors on selected cells, primary or transformed, derived from the seminiferous epithelium. These studies will define the role of SGF in regulating proliferation of spermatogonia (Ao/As) and somatic cells of the mammalian testis, and suggest possible applications to enhance or interfere with normal fertility, and potential actions in pathological processes, including idiopathic oligospermia and aspermia and testicular oncology.
|Baker, J; Hardy, M P; Zhou, J et al. (1996) Effects of an Igf1 gene null mutation on mouse reproduction. Mol Endocrinol 10:903-18|