We examined the effects on fetal testicular steroidogenesis of selected growth and paracrine factors, including ac-tivin, inhibin, EGF, IGF-1, IFG II, NGF, BDNF, VIP, and PACAP-27. They had no effect on fetal testicular steroidogenesis, except for VIP and PACAP-27. These peptides stimulated fetal testicular steroidogenesis very significantly, but, interestingly, no effects were found on BLT-1 cells (an adult mouse Leydig tumor cell line) or purified adult rat Leydig cells. Hence, this effect is specific for the fetal-type of Leydig cells.
Despite these data indicating the potential importance of VIP and PACAP-27 as developmental regulators, it remains to be established whether VIP is actually produced by the central nervous system (CNS) or the testes of the embryo, or whether VIP is available in sufficient amounts from the placenta or the mother, to stimulate fetal Leydig cells. Some investigators were unable to demonstrate VIP gene expression in the rat embryo CNS or the embryonic membranes of the placenta . It may be that VIP is supplied from a maternal source, as has been suggested by Hill et al. , whose data indicate that maternal tissues provide neuroendocrine support for embryonic growth through a surge of VIP during the early postimplantation development in rodents. In contrast, Waschek et al. were able to show, using in situ and Northern hybridizations, that VIP gene expression is established in the developing mouse CNS at least as early as Ell. buy ampicillin
It is interesting that blockage of VIP function by treating pregnant mice with VIP antagonist from E9.5 to El 1.5 produced growth retardation and microcephaly, but not after the age of El 1.5 . In accordance, the VIP gene is expressed transiently in the fetal superior cervical ganglia at the time of neuroblast proliferation and axonal elongation . This implies that VIP might exhibit its regulatory effect on growth and development of the nervous system transiently in a specific period of development. If the same situation prevails in fetal testes, VIP might be the factor that turns on and maintains the first phase of fetal testicular steroidogenesis.