EVALUATION OF EFFECTS OF OVARIECTOMY AND TREATMENT WITH ESTROGEN-REPLACEMENT THERAPY OR SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERM) ON VOIDING FUNCTION AND P2X RECEPTOR EXPRESSION IN THE FEMALE RAT
EVALUATION OF EFFECTS OF OVARIECTOMY AND TREATMENT WITH ESTROGEN-REPLACEMENT THERAPY OR SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERM) ON VOIDING FUNCTION AND P2X RECEPTOR EXPRESSION IN THE FEMALE RAT
TABLE OF CONTENTS
Abbreviations Page 6
Abstract Page 6
Study 1 Page 10
Introduction Page 10
Menopause and the overactive bladder Page 10
Estrogens for the treatment of OAB in post menopausal women Page 12
SERM and tamoxifen Page 15
Materials and methods Page 17
Assigning rats into 4 (acute) week and 24 (chronic) week sham and OVX groups and drug treatment groups Page 17
Treatment of ovariectomized rats with subcutaneously-placed slow release pellet of estrogen, progesterone or tamoxifen (SERM) or associated placebo pellet Page 18
Surgical implantation of catheters on sham, OVX and drug treated rats Page 19
Conscious cystometry for sham OVX and drug treated rats Page 20
Statistical Analysis Page 24
Results Page 25
Study 2
Introduction Page 35
P2X receptor involved in bladder function Page 35
P2X receptor in afferent nerve activity Page 36
The role of P2X receptor in humans Page 37
Materials and methods Page 39
Preparation and homogenization of bladder tissue samples and prefiltration
Page 39
RNA purification and cDNA synthesis Page 40
Quntitative PCR (Taqman) Page 41
Results Page 43
Discussion Page 54
Study 1 Page 54
Study 2 Page 60
References Page 63
Appendix Page 71
ABBREVIATIONS
21 E 21 day 17-estradiol; with 21 day progesterone placebo
21 E+P 21 day 17 -estradiol; with 21 day Progesterone25.0
21 E-plac 21 day 17 -estradiol placebo
21 T 21 day Tamoxifen
21 T-plac 21 day Tamoxifen placebo –mATP Alpha, Beta Methylinated Adenosine Triphosphate
ATP Adenosine Triphosphate
BERKO Estrogen Receptor Beta Knock Out
TABLE OF CONTENTS
Abbreviations Page 6
Abstract Page 6
Study 1 Page 10
Introduction Page 10
Menopause and the overactive bladder Page 10
Estrogens for the treatment of OAB in post menopausal women Page 12
SERM and tamoxifen Page 15
Materials and methods Page 17
Assigning rats into 4 (acute) week and 24 (chronic) week sham and OVX groups and drug treatment groups Page 17
Treatment of ovariectomized rats with subcutaneously-placed slow release pellet of estrogen, progesterone or tamoxifen (SERM) or associated placebo pellet Page 18
Surgical implantation of catheters on sham, OVX and drug treated rats Page 19
Conscious cystometry for sham OVX and drug treated rats Page 20
Statistical Analysis Page 24
Results Page 25
Study 2
Introduction Page 35
P2X receptor involved in bladder function Page 35
P2X receptor in afferent nerve activity Page 36
The role of P2X receptor in humans Page 37
Materials and methods Page 39
Preparation and homogenization of bladder tissue samples and prefiltration
Page 39
RNA purification and cDNA synthesis Page 40
Quntitative PCR (Taqman) Page 41
Results Page 43
Discussion Page 54
Study 1 Page 54
Study 2 Page 60
References Page 63
Appendix Page 71
ABBREVIATIONS
21 E 21 day 17-estradiol; with 21 day progesterone placebo
21 E+P 21 day 17 -estradiol; with 21 day Progesterone25.0
21 E-plac 21 day 17 -estradiol placebo
21 T 21 day Tamoxifen
21 T-plac 21 day Tamoxifen placebo –mATP Alpha, Beta Methylinated Adenosine Triphosphate
ATP Adenosine Triphosphate
BERKO Estrogen Receptor Beta Knock Out
References: Estrogens for the treatment of OAB in post menopausal women The lower urinary tract is sensitive to the hormonal changes in endogenous hormone levels (Robinson and Cardozo, 2003)