Effects of oestradiol-17 beta and 5 alpha-dihydrotestosterone on guinea-pig prostate smooth muscle cell proliferation and steroid receptor expression in vitro.
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-17 beta (OE2) and 5 alpha-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 x 10(4) 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 x 10(4) 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 OE2 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.(ABSTRACT TRUNCATED AT 400 WORDS)
Ricciardelli
C
C
Department of Surgery, School of Medicine, Flinders University of South Australia, Bedford Park.
Horsfall
D J
DJ
Sykes
P J
PJ
Marshall
V R
VR
Tilley
W D
WD
D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D018076:DNA, Complementary / Q000235:genetics; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005821:Genetic Techniques; D006168:Guinea Pigs; D008297:Male; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011467:Prostate / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011944:Receptors, Androgen / Q000187:drug effects; D011960:Receptors, Estrogen / Q000187:drug effects
D018076:DNA, Complementary; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D013196:Dihydrotestosterone; D004958:Estradiol; D004247:DNA