Paracrine interaction in testicular somatic cells.
Initiation of spermatogenesis is regulated by signals derived from intratubular Sertoli cells as well as extratubular Leydig cells, both being systemic targets of hypophyseal gonadotropins. In addition to Leydig and Sertoli cells, a number of other cell types are present in the testis viz. peritubular cells, macrophages and vascular components. The specific paracrine functions of these cells are only partially understood. The peritubular and Sertoli cells form the structural scaffold of the germinal epithelium and are responsible for intratubular pressure, release and transport of spermatozoa and the formation of the blood-testis barrier. We have performed ex vivo and in vitro studies on the ultrastructure of peritubular and Sertoli cells and the distribution of steroid hormone receptors, cytoskeletal and extracellular matrix proteins using rat testes from different stages of postnatal development. Morphological observations were related to in vitro findings of gene expression on the respective hormones and structural proteins. In the developing rat testis, the peritubular cells showed a strong and consistent expression of fibronectin, entactin, laminin as well as the glucocorticoid, androgen, estrogen and partially also the progesterone receptor, while the Sertoli cells were devoid of glucocorticoid receptor and entactin. The glucocorticoid receptor was present in around 20% of the intratubular germ cells (in the 2nd postnatal week) and in 50% of the peritubular cells. In Leydig cells also, the expression reached its climax in the 3rd weak and declined thereafter. This is perhaps pointing to a differentiation-inhibiting role of glucocorticoids in gonocyte differentiation. In the 3rd developmental week, the androgen receptor was present in about 15% of all gonocytes and later in 50% of peritubular cells and about 40% of interstitial cells. The estrogen receptor was absent in peritubular cells of the adult testis. The progesterone receptor was present in about 30% of the peritubular and 25% of the Leydig cells. Taking into account the significant increase in seminiferous tubules following postnatal developmental day 18, the peritubular cells seem to exert an androgen dependent growth stimulus to the seminiferous cords perhaps via the Sertoli cells. In vitro studies of peritubular and Sertoli cells cultured either alone or in co-culture showed by RT-PCR the expression of the androgen and the glucocorticoid receptors in both cell types, as well as fibronectin. Secretion of fibronectin occurred in a clear-cut time-dependent increase in monocultures of peritubular cells (on day 3 of culture). In co-cultures of Sertoli and peritubular cells, fibronectin bio- synthesis was down-regulated. The paracrine interplay between extracellular matrix and hormonal signals joining peritubular and Sertoli cells is essential in the differentiation of the seminiferous tubules.