Immunohistochemical Localization of Insulin-like Growth Factor (IGF-I), IGF-I Receptor, and IGF Binding Proteins 1–4 in Human Fallopian Tube at Various Reproductive Stages

Abstract

Despite the existence of numerous data regarding the insulin-like growth factor (IGF) system in reproductive tissues, especially uterine and ovarian, very little information is available concerning their presence in oviductal/fallopian tube tissue. To elucidate this, the present study was undertaken to determine the presence and cellular distribution of IGF-I, IGF-I receptor (IGF-IR), and IGF binding proteins (IGFBP) 1-4 in human fallopian tubes during various reproductive stages, by means of immunohistochemical analysis with specific antibodies to IGF-I, IGF-IR and IGFBPs 1-4. The primary site of immunoreactivity for these proteins in fallopian tube tissue was in the epithelial lining of the tubes, with substantially lower intensity in the smooth muscle layer, fibroblasts of the serosal tissue, and arteriolar endothelial and smooth muscle cells. The immunostaining was associated with both ciliated and nonciliated tubal epithelial cells without substantial differences in their intensity. There were also no differences in immunoreactivity of IGF-I, IGF-IR, and IGFBPs 1-4 present in ampullary vs. isthmus region of the tubes. Specimens obtained 5-12 years post tubal ligation stained similarly to sections from unligated tubes taken during the same phase of the cycle. The intensity of immunostaining for the IGFBPs was greatest for IGFBP-1, followed by IGFBP-4, then IGFBP-2 and IGFBP-3, with 2 and 3 having similar intensities. The immunostaining intensity of IGF-I, IGF-IR, and IGFBPs in fallopian epithelial cells was cycle-dependent and considerably higher in late proliferative and early-mid secretory compared to late secretory phases, with little immunostaining in the early proliferative phase of the menstrual cycle and postmenopausal period. In summary, the immunohistochemical study reported here demonstrates the presence of IGF-I, IGF-IR, and IGFBPs 1-4 in the human fallopian tube during various reproductive stages. These data suggest an autocrine/paracrine role for the IGF-I system in fallopian tube function, and their cyclic dependency further implies ovarian steroidal regulation.