Synergistic action of steroids and spermatocele fluid on in vitro proliferation of prostate stroma

J Urol. 1998 Jun;159(6):2202-9. doi: 10.1016/S0022-5347(01)63306-8.

Abstract

Purpose: Our goal is to understand human prostate growth phenomena potentially important to BPH development and growth. The objective of the present study is to characterize in vitro prostate stromal proliferative factors in testis epididymal secretions.

Materials and methods: Human spermatocele fluids were used as a source of testicular epididymal plasma (STEP). Primary cultures of human prostate stromal cells were routinely grown in RPMI-1640 with 10% fetal bovine serum. During a 6-day experimental period, cells were cultured in RPMI-1640 in the absence of serum but supplemented with ITS. Whole STEP, ether stripped STEP, or heparin affinity column treated STEP was included in the culture medium with and without the addition of testosterone (T), dihydrotestosterone (DHT), or estradiol (E). Results of these treatments were assessed by cell counts. Antibodies against smooth muscle myosin heavy chain, smooth muscle alpha actin, and prolyl-4-hydroxylase were utilized in immunocytochemical characterization of cultured cells.

Results: Whole STEP stimulated prostatic stromal cells derived from prostates of 15, 45, 70 and 72-year-old men. Treatment of STEP by ether stripping or heparin affinity column exposure did not result in a significant reduction in cell counts. With the exception of the 15-year-old specimen, addition of T or DHT to ether stripped STEP resulted in a significant increase in cell counts over that of ether stripped STEP treatment alone. Preliminary immunocytochemical evaluation indicated the presence of variable mixture of fibroblasts, myofibroblasts, and smooth muscle cells in these cultures.

Conclusions: These in vitro observations indicate that testis epididymal secretions contain androgen/STEP synergistic and androgen independent STEP factors promoting prostate stromal growth. These factors are not heparin binding. These observations are consistent with the concept that, in addition to the production of steroids, the testis produces non-androgenic factors that act in concert with, as well as independently of, androgen to stimulate prostatic growth.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Androgens / pharmacology*
  • Blotting, Western
  • Cells, Cultured
  • Chromatography, Affinity
  • Dihydrotestosterone / pharmacology
  • Estradiol / pharmacology
  • Exudates and Transudates / physiology
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Prostate / cytology*
  • Prostate / growth & development
  • Prostate / physiology
  • Prostatic Hyperplasia / physiopathology
  • Spermatocele / metabolism
  • Spermatocele / physiopathology*
  • Stromal Cells / physiology
  • Testis / physiology*
  • Testosterone / pharmacology

Substances

  • Androgens
  • Dihydrotestosterone
  • Testosterone
  • Estradiol