In the seminiferous tubules of mammalian testis, the activity of somatic cells is synchronized with the ongoing maturation of germ cells. Although there is abundant functional evidence of germ cell-somatic cell interaction, the nature of the biochemical signals exchanged between these cells of the seminiferous epithelium is not known. In the attempt to clarify the paracrine and autocrine regulatory mechanisms involved in the maintenance of the function of the male gonad, we have initiated studies to evaluate the possibility that purines act as local modulators in the testis. The overall aim of this research proposal is to study the role of purines as local messengers for cell-cell interaction and as modulators of hormonally regulated functions of the Sertoli cell. Our preliminary observations demonstrate the presence of purine receptors in vivo in the seminiferous tubule, and our studies in vitro indicate that purine receptors are coupled to a mechanism that causes inhibition of FSH-dependent responses in the Sertoli cell. It is proposed to further characterize purine receptors and their relation to other membrane components on Sertoli cells and germ cells of the seminiferous tubule. The mechanisms by which purines affect Sertoli cell and germ cell functions will be investigated. The hormonal and developmental regulation of the expression of purine receptors in the Sertoli cell will be studied using in vitro and in vivo models. In order to establish the physiological role of purines, the effect of local treatment with purine agonists and antagonists will be correlated with the function of the Sertoli cell. Furthermore, changes in purine binding and purine modulatory effects will be followed during the seminiferous tubule cycle. The information obtained will be valuable in understanding the mechanisms that control the formation of the male gamete. The research proposed is relevant to the development of male contraceptive agents, as it will provide pharmacological methods of inhibiting the function of the Sertoli cell and thereby suppressing spermatogenesis.
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