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|Title:||Effects of oestradiol 17-β and 5α-dihydrotestosterone on guinea-pig prostate smooth muscle cell proliferation and steroid receptor expression|
|Citation:||Journal of Endocrinology, 1994; 140(3):373-383|
|C Ricciardelli, D J Horsfall, P J Sykes, V R Marshall and W D Tilley|
|Abstract:||Smooth muscle cells (SMCs) are the major cellular component of the prostatic stroma. The aim of this study was to examine the effects of oestradiol-17β (OE2) and 5α-dihydrotestosterone (DHT) on the proliferation of guinea-pig prostate SMCs in vitro. OE2 stimulated SMC DNA synthesis at all concentrations examined. At a plating density of 3·0 × 104 cells/cm2, maximal incorporation of [3H]thymidine (136% of control) was observed after 36 h of treatment with 1 nmol OE2/l. At the same plating density, DHT had an inhibitory effect on SMC DNA synthesis, with maximal effects (73% of control) being observed 24 h after treatment with 1 nmol DHT/l. These effects of OE2 and DHT were prevented by co-incubation with specific steroid receptor antagonists. At a threefold lower plating density (1·0 × 104 cells/cm2), the maximal stimulatory and inhibitory effects of OE2 and DHT were delayed by approximately 24 and 12 h respectively. At the lower plating density, a biphasic effect of DHT was observed on DNA synthesis; DHT was both inhibitory and stimulatory. Maximal inhibition (71% of control) and maximal stimulation (168% of control) were observed after 36 and 134 h treatment with DHT respectively. At the lower plating density, longer term treatment of SMC cultures with OE2 and DHT also resulted in an increase in cell number. After 7 days of treatment with OE2 and DHT, cell number increased by 13% and 12% respectively. When OE, and DHT were added in combination, the short-term inhibitory effect of DHT on SMC DNA synthesis was dominant over the stimulatory effect of OE2. Treatment with DHT for 24 h significantly inhibited OE2-induced stimulation of [3H] thymidine incorporation, irrespective of the prior duration of OE2 treatment. At the lower plating density, OE2 also decreased oestrogen receptor (ER) mRNA levels to 38% of control levels after 24 h of treatment. ER mRNA levels remained repressed until 72 h after treatment with OE2, and returned to control values following 96 h of treatment. Both the androgen-induced inhibition and stimulation of DNA synthesis observed following treatment of SMCs with 1 nmol DHT/l were associated with a reduction in androgen receptor (AR) mRNA levels. At an intermediate time (i.e. 48 h after commencement of treatment with DHT) AR mRNA levels were increased more than twofold over control levels. The increase in AR mRNA levels at 48 h after DHT treatment only occurred in cells plated at the lower density, suggesting that this is an essential requirement for the longer term stimulation of prostatic SMC proliferation by DHT.|
|Keywords:||Muscle, Smooth; Prostate; Cells, Cultured; Animals; Guinea Pigs; Dihydrotestosterone; Estradiol; Receptors, Androgen; Receptors, Estrogen; DNA; DNA, Complementary; Genetic Techniques; Cell Division; Base Sequence; Molecular Sequence Data; Male|
|Rights:||© 1994 Bioscientifica|
|Appears in Collections:||Medicine publications|
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