Papel do fator de inibição da migração de macrófagos (MIF) no desenvolvimento púbere da próstata ventral de camundongos

Abstract

The macrophage migration inhibitory factor (MIF) is a multifunctional pleiotropic protein that can activate anti-apoptotic, pro-proliferative and pro-inflammatory mechanisms. Although it is expressed in the prostate, its importance in this gland is not fully understood. So, the contribution of MIF for the development of ventral prostate was evaluated in pubertal and adult mice. Mice aged 30 or 60 days from C57BL/6 WT (wild type) and MIF-/- (knockout) lineages were used for this study. Serum testosterone quantification, histological analyses, immunohistochemistry (alpha-actin, vimentin, PCNA, AR, WNT5a) and western blotting for ERK1/2 were performed. Testosterone serum levels were much higher in MIF-/-30 mice, which shows a greater androgenic signaling in this group. Although body weight in MIF-/-60 and prostate weight in MIF-/-30 were greater than their wild-type pairs, body and prostate weight gain throughout pubertal stage was much lower in MIF-/- animals. MIF-/-30 showed a reduction in epithelium, an increase in lumen and decreased collagen and smooth muscle cells contente in the prostate. As regards cell proliferation, there was an important reduction in MIF-/- mice of both ages. Additionaly, pubertal MIF-/- mice presented elevated ERK activation and also increased score of AR and WNT5a in prostate. During the course of prostate development, the changes found in wild-type mice are expected but in MIF-/- group it is already very evident at 30 days, demonstrating that the absence of MIF antecipates the pubertal development. Therefore, MIF has an important role in stimulating proliferation and controling androgenic stimulli, which contributes to the temporal coordination of the course of prostate development from puberty to adulthood.