title: Proliferative activity and branching morphogenesis in the human prostate: a closer look at pre- and postnatal prostate growth.
abstract: BACKGROUND
  To gain further insight into the molecular cell biologic features of prostate development, we investigated the proliferative activity of prostate epithelial and stromal cells and their topographic relationship with neuroendocrine (NE) cell distribution and regional heterogeneity.
  
  
  METHODS
  Consecutive sections from 43 prostates taken during autopsy representing fetuses (12-38 weeks of gestation), infants, prepubertal males and adults were double stained for chromogranin A and MIB-1. MIB-1 labeling index (LI) was calculated in the budding tips, forming acini, major collecting ducts, adjacent and non-adjacent stromal compartments. Furthermore, the topographic relationship between proliferating cells and NE cells was evaluated.
  
  
  RESULTS
  In the first half of gestation, cell proliferation as revealed by MIB-1 LI was significantly higher in epithelial structures and stroma than in older fetuses and other age groups. MIB-1 LI was higher in budding tips than in other epithelial regions. MIB-1 LI in stroma adjacent to budding tips was not higher than that adjacent to other epithelial branching segments. Co-expression of chromogranin A and MIB-1 staining was not observed. MIB-1 LI was lower in cells in the direct vicinity of chromogranin A positive NE cells than at a distance from NE cells.
  
  
  CONCLUSIONS
  Prostate development in the first half of gestation is explosive. Thereafter, the prostate basically is a slow-growing organ. Budding tips are the major growth foci during early prostate development, while stromal growth is evenly distributed throughout the prostate, probably indicating that stromal-epithelial interactions do not manifest in enhanced proliferation at their interface. NE cells may have an inhibitory effect on proliferation of exocrine epithelial cells and are probably only associated with differentiation of prostate exocrine cells in the prostate.
authors.affiliation: Department of Urology, University Medical Centre Nijmegen, The Netherlands.
authors.forename: Y
authors.initials: Y
authors.lastname: Xue
authors.forename: G
authors.initials: G
authors.lastname: Sonke
authors.forename: C
authors.initials: C
authors.lastname: Schoots
authors.forename: J
authors.initials: J
authors.lastname: Schalken
authors.forename: A
authors.initials: A
authors.lastname: Verhofstad
authors.forename: J
authors.initials: J
authors.lastname: de la Rosette
authors.forename: F
authors.initials: F
authors.lastname: Smedts
mesh_terms: D000328:Adult; D034961:Antigens, Nuclear; D002648:Child; D002675:Child, Preschool; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D019394:Ki-67 Antigen; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D011247:Pregnancy; D011467:Prostate / Q000166:cytology / Q000196:embryology* / Q000254:growth & development*; D018709:Statistics, Nonparametric; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D053379:Chromogranin A; D002864:Chromogranins; D019394:Ki-67 Antigen; D009687:Nuclear Proteins