Prostatic stromal cell phenotype is directly modulated by norepinephrine.
OBJECTIVE
To evaluate the response of prostatic stromal cells in vitro to the action of the agonist norepinephrine and to examine the role of cell density in this response.


METHODS
Stromal cells isolated from transurethral chippings of patients with benign prostatic hyperplasia (BPH) were seeded onto tissue culture dishes either at high density (9 x 10(3) cells/cm2) or at low density (1.5 x 10(3) cells/cm2). Norepinephrine was added at concentrations in the range of 2.5 to 50 microM. Cells were harvested at the moment of confluence, labeled with monoclonal antibodies to four cytoskeletal proteins, and analyzed by flow cytometry.


RESULTS
Sparsely plated stromal cells showed a consistent biphasic response in which a small fall in immunofluorescence occurred in the range of 5 to 15 microM norepinephrine but was thereafter followed by a progressive rise in fluorescence to 50 microM, indicating increased expression of smooth-muscle-associated cytoskeletal proteins. The shape of flow-cytometric frequency-distribution histograms for smooth-muscle myosin, desmin, and talin suggested that all mesenchymal cells in the stromal cultures were similarly modulated by norepinephrine. However, the effect on smooth-muscle actin was different in that a subpopulation of hyperreactive cells was identified. Densely plated stromal cells did not show a similar biphasic response to norepinephrine but instead demonstrated an overall downward trend, indicating a progressively diminished expression of these cytoskeletal proteins.


CONCLUSIONS
Norepinephrine stimulation directly modulates BPH-derived prostatic stromal cells toward a differentiated smooth-muscle phenotype as evidenced by increased expression of cytoskeletal proteins. The effect of norepinephrine on cultures is cell-density-dependent, suggesting that intercellular communication is an important factor in coordinating the differentiation responses. This study has revealed a specific interaction between physical and humoral stimuli, which influences in part the phenotype of prostatic stromal cells. Such interaction is likely to determine the development of clinical BPH, and also the response of any individuals following therapeutic intervention using selective alpha-adrenergic blockade.
Smith
P
P
Department of Pathology, University of Liverpool, United Kingdom.
Rhodes
N P
NP
Beesley
C
C
Ke
Y
Y
Foster
C S
CS
D002452:Cell Count; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D010641:Phenotype; D011467:Prostate / Q000166:cytology* / Q000502:physiology*; D017154:Stromal Cells
D009638:Norepinephrine