The castration-induced regression and testosterone stimulated regrowth of the vasculature in the rat ventral prostate lobe were studied using stereological techniques. Seven days after castration, the endothelial cell proliferation rate (bromodeoxyuridine labeling index); the total weights of blood vessel walls, blood vessel lumina, endothelial cells, glandular epithelial cells; and total organ weight were all decreased. Within 2 days after sc treatment with testosterone, the total weights of blood vessel walls, endothelial cells, and vascular lumina, as well as the endothelial cell proliferation rate, were all normalized. In contrast to the rapid response of the vasculature, the total weight of glandular epithelium and total organ weight were not normalized during the 4 days of testosterone treatment. Growth of the vasculature apparently precedes growth of the glandular epithelium. The testosterone-dependent factors stimulating the vasculature are unknown, but factors derived from epithelial cells, mast cells (which accumulate in the prostate during the first day of testosterone treatment), and tissue macrophages could all be involved. Castrationinduced regression and testosterone-stimulated regrowth of the prostatic vasculature can be used as an experimental model to study factors regulating angiogenesis and organ growth in the prostate. (Endocrinology 139: [451][452][453][454][455][456] 1998) V ASCULAR density and vascular invasion are related to the risk of extraprostatic growth (1), metastasis (2, 3), disease progression (4), and cancer-specific survival (5) in prostate cancer patients. In addition, the growth of a human prostate cancer cell line (PC3) in nude mice is remarkably inhibited after treatment with the angiogenesis inhibitor angiostatin (6). The castration-induced involution of the rat ventral prostate is preceded by a marked decrease in organ blood flow (7). These recent observations suggest that the vasculature could play a more central role in the regulation of the normal prostate and prostate tumors than earlier recognized. The factors controlling blood flow, endothelial cell proliferation, and other aspects of angiogenesis in the normal prostate and in prostate cancers are however largely unknown.Previous studies have suggested that castration reduces endothelial cell numbers and the endothelial cell proliferation rate in the adult rat ventral prostate, and that they are normalized by testosterone treatment (8). Similarly, castration decreases and testosterone treatment rapidly normalizes blood flow to the adult rat ventral prostate (7). These studies indicate that the vasculature could be regulated, directly or indirectly, by androgens. If this is the case, castrationinduced involution and testosterone-stimulated regrowth could be used to study factors regulating angiogenesis, vascular growth, and local blood flow in the normal prostate, and to examine the role of vascular factors in prostate physiology and pathology. The aim of this study therefore was to examine, in detail, how...