Non-steroidal growth factors are mainly polypeptides that upon binding to surface receptors in target cells elicit the activation of signal transduction pathways involved in cell division and cell specific differentiation. The action of growth factors can be stimulatory or inhibitory as shown using cultured testicular cells. Since growth factors elicit diverse effects in variety of organ systems during development, it has been difficult to establish and to assign a specific function to a specific growth factor during the process of spermatogenesis. Situation is further complicated by the fact that several of these factors (FGF, IGF) have been found in Sertoli cells and germ cells. On the other hand, EGF and TGF have been specifically implicated in the survival and proliferation of rat type A-spermatogonia.
INHIBIN FAMILYInhibin and activin are dimeric glycoproteins sharing a common-p subunit. Inhibin contains an inhibin specific a-subunit and one of the two closely related-P subunits (PA or P,), whereas activin is a homo-or heterodimer of P-subunits. Imrnunoreactive and bioactive inhibin, and three inhibinlactivin subunit mRNAs (a, PA, and P,) were identified in Sertoli cells. Small amounts of imrnunoactive inhibin, inhibin a-subunit proteins and activin, and the subunit rnRNAs were also detected in the Leydig cells of rat testis and in Leydig derived cell lines.
InhibinInhibin isolated from follicular fluid is a heterodimeric glycoprotein that exists in multiple biologically active forms. Porcine inhibin is a 32-kDa protein, which is composed of two disulfide bound subunits of 18kDa (a) and 14 kDa (P). Two related, yet distinct forms of the smaller p subunit, termed PA and p, have been described, and both these subunits form complex with the a-subunit to form biologically active inhibin (termed inhibin A and inhibin B). The amino acid sequences of inhibins for porcine, bovine, human, and rat sources have been described by molecular cloning of the corresponding cDNAs. Structural analysis has revealed that each of the three inhibin subunits is encoded by a separate gene and that each mature subunit resides at the carboxy terminal end of a much larger precursor protein. In addition, the subunits of inhibin share a substantial sequence identity with an emerging family of proteins with growth regulating properties, the prototype of which is transforming growth factor+ (TGF-P).