Insulin-Like Growth Factor-I Produced by Seminal Vesicles: Relationship to Intraepithelial Basal Cell Hyperplasia in the Prostate

Abstract

Purpose: This study examined the seminal vesicle fluid (SVF) as a potential local source of insulin-like growth factor-I (IGF-I) in the peripheral zone of the prostate. Experimental Design: IGF-I levels in seminal fluid were measured. The levels of the IGF-I receptor (IGF-IR) in its active, phosphorylated form as well as direct downstream targets were examined in the peripheral zone of the prostate. Results: In situ, we find that the IGF-IR is activated in the peripheral zone in areas of atrophy, prostatic intraepithelial hyperplasia, and cancer. In addition, immunostaining reveals preferential activation of the IGF-IR in p63-positive cells in areas of intermediate basal cell hyperplasia in the peripheral zone, indicating that prostate progenitor cells are highly sensitive to increases in local IGF-I levels. These areas of basal cell hyperplasia occur at high incidence in the peripheral zone of the prostate. Relatively high levels of IGF-I were identified in SVF. In addition, we find that SVF can stimulate the proliferation of both normal and cancer-derived prostate cells. Conclusions: These results suggest that SVF is a local source of IGF-I that provides chronic stimulation of prostate cells. This chronic stimulation could contribute to the development of prostate cancer in older men.Prostate cancer exhibits a prominent zonal distribution. The peripheral zone harbors over 70% of prostate cancers, and this region of the prostate is also the primary site of high-grade prostatic intraepithelial neoplasia (HGPIN; ref. 1). In terms of tissue architecture, glands throughout the prostate are characterized by a basal cell compartment, which is believed to include potential stem cells, and a secretory compartment (2, 3). Cells within the basal cell compartment may represent the population that undergoes malignant transformation during the formation of prostate cancer (4, 5). The regional variation in prostate cancer suggests that basal cells within the peripheral zone are affected by the presence of local factors responsible for differential progression of the disease. A greater understanding of the zonal distribution of basal cells and the local factors that influence their proliferation and/or differentiation might help explain the localization of precursor lesions and prostate carcinoma.In an attempt to identify local factors that influence cell proliferation and differentiation in the prostate, we have examined seminal vesicle fluid (SVF) as a source of insulinlike growth factor-I (IGF-I). This effort was prompted by the growing realization of the importance of local production of IGF-I. Both IGF and IGF binding proteins have been identified in the semen (6 -8), but the recent focus of interest has been on circulating IGF as a potential indicator of relative risk for prostate cancer. The seminal fluid is a potential source of factors that influence the peripheral zone of the prostate specifically because the ejaculatory ducts merge with the urethra upstream of the terminal ducts of the peripheral zone.In h...

Nutrition regulation of male accessory gland growth and maturation in Tribolium castaneum

“…melanogaster , some co-factors responding to nutritional signals may induce/activate ILP3 45 . In vertebrates, male reproductive tract also could be a local source of IIS as shown in the seminal vesicle 46 and in the cells of human prostate 47 . Therefore, MAG is a good system to study IIS pathway function in the peripheral tissues.…”