English

Abstract

Introduction The authors hypothesized a possible use of prolactin as a therapeutic treatment of skin lesions. We investigated the relationship between topic prolactin-treatment of skin lesions and wound healing process in rats. Materials and methods Skin lesions were produced in both control and experimental rats. PRLtreatment (100 μl of PRL 2 ng/ml in PBS) was performed by dripping on lesions of experimental rats. Control rats were treated with only PBS. After 1 week, fragments of tissue from the bottom of lesions were obtained from three rats of both control and experimental groups. The authors continued the PRL-treatment to other rats until complete healing. In skin specimens, analysis of the ultrastructural features of cells, cellular aggregates and extra-cellular matrix components were made by transmission electron microscopy. In skin specimens, computerized morphometry measurements of different cell types were also made. Results Results showed that progression of the healing process was more advanced in treated rats as evidenced by the different percentages of distinct cell types after 1 week of PRLtreatment. Moreover, in treated rats, the healing process was slightly faster than that in the control ones (11– 12 days vs. 14–15 days, respectively). Conclusion Results of our study supported the idea of a role of PRL on wound healing, thanks to its effects on both angiogenesis and keratinocyte proliferation in re-epithelialization and then on restoration of injured skin. Introduction Wound healing of skin lesions is a process well known in relation to histological alterations, even if the molecular mechanisms underlying its regulation are still unclear. Several growth factors and cytokines of the immune response are involved in it1, as well as macrophages producing cytokines stimulating growth of new capillaries (angiogenesis), collagen synthesis and production of fibres2. Wound healing proceeds through a dynamic process that includes the inflammatory phase, the proliferative phase with generation of granulation tissue, the phase of reepithelialization and of remodelling. If the healing process does not occur regularly, this may be responsible for some pathological conditions such as ulcers or chronic injuries3,4. In the inflammatory phase, neutrophils and macrophages implement a cleaning action in the injury, removing cellular debris, foreign bodies and any contaminating bacteria. Macrophages also stimulate migration of endothelial cells and fibroblasts, thus the beginning of two fundamental processes of wound healing: angiogenesis and fibroplasia. The proliferative phase of wound healing is characterized by fibroplasia, angiogenesis, epidermal regeneration and wound contraction. Angiogenesis is a fundamental step in the proliferative phase. New blood vessel generation and thus blood flow allow restoring blood supply in the area of the lesion. The last event of the proliferative phase is the re-epithelialization. It results in the regeneration of an intact epidermal layer above the new tissues. This process is supported by keratinocytes that move through the granulation tissue. When wound surface is covered by a monolayer of keratinocytes, migration stops and a new stratified epidermis is restored. The remodelling phase is characterized by collagen degradation and synthesis of new ECM components. The remodelling phase depends mainly on the breakup/building of ECM; macrophages play a crucial role in both processes5,6. Each stage of wound healing is due to paracrine effectors released by specific cell-types of immune systems and also to some endocrine effectors known from the literature7–9. Prolactin (PRL) belongs to the latter group and is a peptide hormone secreted by the anterior hypophisis. PRL is a hormone secreted by acidophilic cells of the pituitary gland, and it is known for its lactogen action on the mammary gland. It has specific roles in regulating both humoral and cell-mediated immune response. In recent years, a lot of evidence10 indicates that several other tissues are able to produce PRL. The discovery of a PRL extrapituitary production11,12 has proposed a revaluation of this versatile bio-regulator, which acts systemically as a hormone, and locally as a cytokine13. The different isoforms of PRL exhibit distinct biological * Corresponding author E-mail: g.musumeci@unict.it. 1 Department of Bio-Medical Science, Section of Human Anatomy and Histology, University of Catania, Catania, Italy. 2 Department of Internal Medicine, University of Catania, Catania, Italy. 3 Department of Surgery, University of Catania, Catania, Italy.