Prolactin's mitogenic action on the pigeon crop-sac mucosal epithelium involves direct and indirect mechanisms

It has long been known that prolactin (PRL) induces proliferation of the mucosal epithelial lining of the pigeon crop-sac. This system was used to study possible interactions of other hormones with PRL's mitogenic effect directly on the crop-sac cells. Injection of a sheep pituitary powder into the loose skin between the leg and abdomen of pigeons increased the responsiveness of the crop-sac to direct, local application of PRL. Similar systemic injections of anterior pituitary hormones, ACTH and TSH (alone or together), or a combination of LH and FSH, were without effect on the local response to PRL. However, systemically injected PRL and GH resulted in a dramatic augmentation of the response of the organ to local injection of PRL. PRL was more potent than GH in this regard. These results suggest that PRL has at least two modes of action as a mitogen on this epithelium--its well-known direct action on the cells and an indirect action as well that is possibly mediated by the secretion of another factor into the blood stream. Because it was previously found that somatomedin-like molecules, including proinsulin, act synergistically with PRL to promote proliferation of these cells when coinjected locally with PRL (T. R. Anderson, J. Rodriguez , D. S. Pitts , E. M. Spencer, and C. S. Nicoll , 1983, In "Insulin-like Growth Factors/Somatomedins," de Gruyter , Berlin), The effects of systemic injections of proinsulin were also tested. Proinsulin had a potentiating effect similar to that of the pituitary powder and of GH or PRL. These results are consistent with the following interpretations: When PRL promotes crop-sac proliferation to produce crop-milk in pigeons and doves, the hormone acts through at least two mechanisms. One of these is a direct effect on the crop-sac, which sensitizes the mucosal epithelium to the mitogenic action of a somatomedin-like growth factor. The second effect is an increase in the production and/or secretion of the factor, which then acts synergistically with PRL to promote proliferation of the crop-sac mucosal cells. More direct evidence for this proposal was provided by the finding that serum from saline- or PRL-treated pigeons did not stimulate crop-sac mucosal growth when it was injected locally. However, the serum from PRL-treated birds had a much higher level of an activity that augmented the effects of PRL when the sera were locally injected in combination with PRL.(ABSTRACT TRUNCATED AT 400 WORDS)