Sex steroids modulate alpha 1-adrenoceptor-stimulated Ca2+ elevation in human cultured prostatic stromal cells.
BACKGROUND
Benign prostatic hyperplasia is an age- and androgen-dependent condition of urethral compression caused by prostatic contractility and glandular enlargement. In this study we investigate whether testosterone, dihydrotestosterone and estradiol modulate the ability of human cultured prostatic stromal cells (HCPSCs) to respond to the adrenoceptor agonists, noradrenaline (30 microM) and phenylephrine (100 microM), the protein kinase C activating phorbol ester, phorbol diacetate (PDA, 10 microM), and the L-type Ca(2+) channel activator, (-)-Bay K8644 (Bay K, 10 microM) with elevations of intracellular Ca(2+) ([Ca(2+)](i)).


METHODS
Cells were loaded with the Ca(2+) sensitive fluorophore, FURA-2AM (10 microM) and changes in intracellular Ca(2+) determined before and 8-12 min after ligand addition.


RESULTS
Compared to steroid-free (SF) controls, the incubation of HCPSC with testosterone (30 and 300 pM) significantly increased responses to both noradrenaline and phenylephrine. Responses to Bay K were significantly reduced between 30 nM to 300 pM but responses to PDA were not greatly affected. Compared to SF the addition of estradiol (E(2), 100 pM) did not affect responses to phenylephrine. The concomitant addition of dihydrotestosterone (DHT) and E(2) (to give ratios from 1:1 to 1,000:1) elevated the responses to noradrenaline and phenylephrine at the extreme ranges. Responses to PDA and Bay K generally increased as DHT:E(2) approached unity.


CONCLUSIONS
These results indicate that sex steroids modulate the activities of HCPSCs through the regulation of both receptors and signal transduction processes.
Nguyen
S T
ST
Prostate Research Co-operative, Faculty of Pharmacy, Monash University, Royal Parade, Parkville, Victoria, Australia.
Prakash
R
R
Anderson
C J
CJ
Frydenberg
M
M
Haynes
J M
JM
D058646:Adrenergic alpha-1 Receptor Agonists; D000368:Aged; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D012739:Gonadal Steroid Hormones / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011467:Prostate / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D058646:Adrenergic alpha-1 Receptor Agonists; D012739:Gonadal Steroid Hormones; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D002118:Calcium