Interactions among prolactin, epidermal growth factor, and proinsulin on the growth and morphology of the pigeon crop-sac mucosal epithelium in vivo.

Abstract

The local pigeon crop-sac assay was used to test the direct effects of epidermal growth factor (EGF) and several other growth factors and hormones on the growth of mucosal epithelial cells in vivo. Insulin, relaxin, multiplication-stimulating activity, proinsulin, and platelet-derived or fibroblast growth factors had no direct stimulatory activity by themselves. Human insulin-like growth factor I and EGF caused dose-related stimulation, but were less effective than ovine (o) PRL. Insulin, platelet-derived growth factor, fibroblast growth factor, and multiplication-stimulating activity did not affect the proliferative response to oPRL when injected along with the hormone. Proinsulin augmented the direct mitogenic action of oPRL, but not that of EGF. When EGF was injected locally with PRL no interaction occurred even though both hormones were independently mitogenic. A single sc injection of a high dose of oPRL (0.5 mg) given at a site distant from the crop-sac had no effect on the mucosal epithelial cells, but it caused a significant increase in their response to the direct action of oPRL. However, the systemically acting PRL did not affect the direct local effect of EGF. The gross pattern of mucosal cell proliferation induced by PRL (parallel ridges resembling gastric rugae) differed from that produced by EGF (usually irregular patches), and PRL, but not EGF, promoted the accumulation of lipid droplets in the stimulated mucosal epithelial cells. Furthermore, the crop mucosal cells in the midline of the organ are unresponsive to PRL, but were highly responsive to EGF. These results indicate that although EGF and PRL are both mitogenic to crop mucosal epithelial cells, the former does not mimic the latter. They produce a different growth pattern, and EGF fails to promote differentiation of the resultant daughter cells. Moreover, EGF is a less specific mitogen than is PRL, and the two hormones do not interact in their mitogenic effects.