PARACRINE FACTORS AND THE REGULATION OF SPERMATOGENESIS

Main problem: Although the gonadotropins and testosterone are required for normal spermatogenesis, it is believed that local control factors regulate spermatogenesis. For many years these regulatory factors had not been identified. Over the past five years, a number of growth fac tors have been identified in testis or isolated testicular cell types or secretions. Growth factors are key regulatory molecules which affec t cell proliferation, meiosis, and differentiated function. These fact ors usually act in an autocrine (acting upon the cell which secreted i t) or paracine (affecting another cell) manner and thus are involved i n intercellular communications. Methods: Growth factor secretion by te sticular cell types or testis tissue has been analyzed using a variety of assays measuring cell proliferation in vitro, as well as assays us ing immunocytochemicals. Growth factor gene expression in testis has b een analyzed by Northern blot analysis and in situ hybridization, whic h gives information concerning the stage and cell specific expression of the gene. Inbred strains of mice with mutations or deletions in a g rowth factor gene has been used to suggest the function of two specifi c factors in testicular development and growth. Results: Among the gro wth factors expressed or secreted by testicular cell types, most are c ommon to some other cell types in the body, such as transforming growt h factors alpha and beta, epidermal growth factor, fibroblast-like gro wth factors, insulin-like growth factors, interleukins, endorphins, in hibin and activin, while others may be more testis specific such as mu llerian inhibiting substance (anti-mullerian hormone) and Sertoli cell secreted growth factor. A variety of proto-oncogenes are expressed at discrete stages of spermatogenesis, as well as by the somatic cells o f the testis. Many of these encode growth factors, receptors or other proteins involved in signal transduction. Conclusion: With the excepti on of the kit ligand and the c-kit proto-oncogene, which have been dem onstrated to play a role in the survival of the primordial germ cell i n the testis during embryogenesis, little is known of the direct role of the other growth factors in spermatogenesis. It is likely that in t he near future that the function of many of these proteins in the regu lation of spermatogenesis will be identified. Eventually, this informa tion will be used to develop specific therapies and diagnostic procedu res for the infertile male.