Female Rabbit Urethra Research Articles

Effects of Long-Term Dietary Soy Treatment on Female Urethral Morphology and Function in Ovariectomized Nonhuman Primates

Agonistic effects of estrogen on the female urethra include an increase in contractile function, blood flow and mucosal hyperplasia. Whether such effects can be achieved by soy based phytoestrogen diets is unclear. We studied the effects of chronic phytoestrogen treatment on the structural and functional properties of the urethra in ovariectomized monkeys. Following ovariectomy 18 monkeys were fed a diet containing soy (9) or casein (9) based protein for 32 months. At necropsy the urethra and bladder were removed and the urethra was separated into 3 segments of equal length, including a proximal, a middle and a distal segment. Each urethral segment and 1 bladder segment was tested in vitro for functional responses to electrical field stimulation and pharmacological stimulation, and the proximal to distal segments were tested for urothelial thickness and mucosal area. Electrical field stimulation produced frequency dependent contractile responses in the bladder, proximal and middle segments but not in the distal segment. Carbachol, phenylephrine and endothelin-1 produced concentration dependent contractions in all urethral segments. The maximum response decreased from the proximal to the distal segment (p </=0.05). The maximum response in the proximal and bladder segments to pharmacological stimulation and electrical field stimulation as well as mucosal area and urothelial thickness were significantly higher in the treatment than in the control group (p < or =0.05). Chronic phytoestrogen treatment results in increased responsiveness of the proximal urethra to pharmacological and electrical stimulation, which is associated with an increase in urothelial thickness and mucosal area. This study indicates that dietary soy may have estrogen agonist effects on the urethra and bladder in estrogen deficient females.

Selectivity of oxymetazoline for urethral pressure vs blood pressure in the anaesthetized female rabbit.

The aim of this study was to test alpha-adrenergic reference agonists for tissue selectivity in the urethra and to pharmacologically characterize the functional alpha-adrenoceptor type of the female rabbit urethra in vivo. The effect of alpha-adrenergic agonists and antagonists on the urethral pressure was compared with that on blood pressure and heart rate measured simultaneously in the anaesthetized female rabbit. Oxymetazoline, NS-49, phenylephrine and phenylpropanolamine enhanced the urethral pressure in a dose-dependent manner. Phenylephrine and phenylpropanolamine also enhanced the blood pressure with significantly lower ED50 (dose that gives half of the maximal enhancing effect) values than for the urethral pressure. This was in contrast to oxymetazoline and NS-49. The ED50 values for oxymetazoline on urethral pressure, and systolic and diastolic blood pressure were 0.00067, 0.0030 and 0.0020 mg/kg, respectively. The ED50 values for NS-49 on urethral pressure, and systolic and diastolic blood pressure were 0.019, 0.21 and 0.18 mg/kg, respectively. Clonidine and UK 14,304 had no effect on urethral or blood pressure. The oxymetazoline-evoked increase in urethral pressure was inhibited by WB-4101 with an ID50 (dose that gives half of the inhibitory effect) significantly lower than that for rauwolscine. The results suggest that in the female rabbit in vivo activation of alpha1-adrenoceptors increased the urethral pressure. Phenylephrine and phenylpropanolamine, in contrast to oxymetazoline and NS-49, selectively enhanced blood pressure as compared with urethral pressure. Provided that the present results also have validity in humans, it would seem possible to develop urethra-selective drugs for treatment of stress incontinence with few or no cardiovascular side-effects.

Shortening velocity is different in longitudinal and circular muscle layers of the rabbit urethra.

The aim of the study was to investigate whether the functional difference between circular and longitudinal muscles in the female rabbit urethra is reflected in their shortening properties and lactate dehydrogenase (LDH) activity. For mechanical experiments the preparations were chemically skinned to avoid influence of membrane-related mechanisms and to enable maximal activation. Force velocity relations and the maximal shortening velocity (v(max)) were determined using the isotonic quick-release method. The v(max) was three times higher in longitudinal muscle. LDH isoform pattern was determined on agarose gels. The M-subunit, favourable for lactate formation, constituted 70% of the total in both types of muscle. There was no difference in the LDH isoform pattern despite the marked difference in v(max). We conclude that the difference in v(max) reflects differences in the contractile machinery itself. These mechanical characteristics are advantageous for the role of the circular as a tonic muscle contracting during bladder filling, and the longitudinal as a phasic muscle active in opening up the urethra during micturition.

Direct effect of amezinium on rabbit urethra: effect of estrogen and progesterone treatment.

The effect of amezinium, a new anti-hypotensive agent, and hormonal treatment on the female rabbit urethra was investigated. Cumulative dose responses were obtained for amezinium and norepinephrine on strips of muscle from the urethras of ovariectomized female rabbits by means of the tissue-bath system. Amezinium enhanced the response to electrical field stimulation and showed a direct contractile response on the urethra. These responses were only about 20% of the maximum norepinephrine response. The contractile response to amezinium was completely blocked by prazosin. When rabbits were pretreated with estrogen, with or without progesterone, for 4 weeks, the response to amezinium increased to 40% of the maximum norepinephrine response. Although amezinium enhances muscle contractile responses to electrical stimulation, this effect is strong when amezinium is used alone; concurrent estrogen treatment improves the effects of amezinium.

Effects of potassium channel inhibitors on nitrergic and adrenergic neurotransmission in lamina propria of the female rabbit urethra.

Electrical field stimulation of strip preparations of the female rabbit urethral lamina propria induces a frequency-dependent adrenergic contraction or a non-adrenergic, non-cholinergic (NANC) relaxation, mediated by nitric oxide, depending on the prevailing tension. To study the role of potassium channels in these responses, the effects of inhibitors of voltage-dependent (dendrotoxin I, 4-aminopyridine), low (apamin) and high (iberiotoxin, charybdotoxin) conductance calcium-activated and ATP-sensitive (glibenclamide) potassium channels on the frequency-response relationship were examined. 4-Aminopyridine (1 mM), but none of the other inhibitors, augmented the NANC relaxation. The maximal response was, however, unaffected by 4-aminopyridine. The adrenergic contraction was enhanced by 4-aminopyridine (1 mM), dendrotoxin I (0.1 microM), iberiotoxin (0.1 microM) and charybdotoxin (0.1 microM), but not by apamin (0.1 microM) and glibenclamide (10 microM). Besides reducing the frequency eliciting half maximal contraction dendrotoxin and charybdotoxin also enhanced the maximal response. None of the inhibitors affected the relaxation induced by the nitric oxide donor 3-morpholinosydnonimine or the contraction elicited by noradrenaline. The results suggest that dendrotoxin-sensitive voltage-dependent and high conductance calcium-activated neuronal potassium channels participate in adrenergic, but not in nitrergic, neurotransmission in the lamina propria of the female rabbit urethra. This offers a possibility to selectively interfere with the adrenergic neuroeffector system with drugs acting on these K-channels.

The l‐arginine/nitric oxide pathway in the rabbit urethral lamina propria

A non-adrenergic, non-cholinergic (NANC)-mediated relaxation has been demonstrated in the female rabbit urethral lamina propria, both in response to electrical stimulation and after administration of acetylcholine. The present study was performed to investigate if these relaxations are mediated via the L-arginine/nitric oxide (NO) pathway. In the lamina propria of the female rabbit urethra, numerous NADPH diaphorase-positive, fine varicose nerve fibres were observed both around arteries, in and around smooth muscle bundles, and in arterial endothelium. Since NADPH diaphorase histochemistry may be a marker of NO synthase-containing neurons, this finding suggests the occurrence of NO synthase in this tissue. Isolated preparations of the rabbit urethral lamina propria, contracted by noradrenaline, produced frequency-dependent NANC relaxations in response to electrical field stimulation, and concentration-dependent NANC relaxations in response to acetylcholine. Electrically induced relaxations were possible to evoke even in preparations where acetylcholine-induced relaxation was poor or absent. Pretreatment with the NO synthase inhibitor, NG-nitro-L-arginine (L-NOARG) reduced the maximum relaxation obtained at 30 Hz to 12% of the control response. NG-nitro-D-arginine (D-NOARG) had no effect. The effects of L-NOARG were antagonized by the addition of L-arginine. Acetylcholine relaxed noradrenaline-precontracted strips by 36%; vasoactive intestinal polypeptide (VIP) reduced the contraction by 95%. L-NOARG, but not D-NOARG, abolished or reversed acetylcholine-induced relaxations, but failed to reduce the relaxations produced by VIP. The results demonstrate the occurrence of NADPH diaphorase-positive nerve fibres in the lamina propria of the female rabbit urethra.(ABSTRACT TRUNCATED AT 250 WORDS)

Nerve-Mediated Functions In the Circular and Longitudinal Muscle Layers of the Proximal Female Rabbit Urethra

In the present study, nerve mediated functions in the circular and longitudinal muscle layers of the female rabbit urethra were characterized. Based on light microscopic findings, the interest was focused on the proximal third of the organ. A microsurgical dissection technique was developed, allowing separation of the two muscle layers. The following studies were carried out: functional in vitro investigations including exogenous application of drugs and electrical field stimulation, investigations of the release of 3H-noradrenaline (NA), and autoradiography for visualization of muscarinic receptors. The results can be summarized as follows: the adrenergic nervous influence, which was mediated mainly via alpha1-adrenoceptors, dominated the contractile response of the circular layer and contributed significantly to the contraction of the longitudinal layer. A previously described fast, non-adrenergic, non-cholinergic response was found in the circular muscle layer. This response should probably be ascribed to striated muscle with a different innervation and/or structure than skeletal muscle in general. Muscarinic cholinoceptors were abundant in the outer parts of the urethral wall and decreased in density in luminal direction. A significant cholinergic contractile component was demonstrated in the longitudinal muscle. A non-adrenergic, non-cholinergic nerve-mediated relaxant response was found in both layers, although more pronounced in the circular one. Vasoactive intestinal polypeptide completely relaxed both circular and longitudinal preparations contracted by noradrenaline. A possible basis for an interaction between adrenergic and cholinergic nerve endings was demonstrated in the circular muscle layer. Stimulation of muscarinic receptors on the adrenergic nerve endings markedly reduced the release of 3H-NA.The present results support the findings in previous studies on circularly and longitudinally oriented full-thickness preparations of the female urethra and further underline the differences in structure, innervation and receptor functions between the different muscle layers of the urethral wall.

尿失禁に対する基礎的研究

The effects of various alpha-adrenergic agonists and antagonists on the contractile properties of the isolated urethra of male and female rabbits were examined and the population of alpha 1- and alpha 2-adrenoceptors, using radioligand receptor binding techniques, was also quantified to define the functional role of postsynaptic alpha-adrenoceptors in urethral smooth muscle. Norepinephrine, epinephrine (non-specific alpha-adrenergic agonists) and phenylephrine (alpha 1-adrenergic agonists) induced increases in contractile force in both the male and female urethra. Clonidine (alpha 2-adrenergic agonist) caused a relatively large contractile response in the female urethra but only a small contractile response in the male urethra. Receptor binding studies indicated that the male urethra contains almost equal amounts of alpha 1- and alpha 2-adrenoceptors (32 vs. 34 fmol/mg protein, respectively) whereas the female urethra contains a significantly greater density of alpha 2- than alpha 1-adrenoceptors (122 vs. 34 fmol/mg protein, respectively). Our studies have indicated that: (1) both alpha 1-and alpha 2-adrenoceptors cause contractile responses in male and female rabbit urethra; (2) the greater response to alpha 2-agonist in female than male urethra is correlated with a higher density of alpha 2-adrenoceptors in this tissue.

Different effects of neuropeptide Y on electrically induced contractions in the longitudinal and circular smooth muscle layers of the female rabbit urethra.

The effects of neuropeptide Y (NPY) on preparations of isolated longitudinal and circular smooth muscle from rabbit urethra were studied. In both types of muscle, electrically induced contractions and relaxations could be abolished by tetrodotoxin, (TTX). In the longitudinal muscle preparations the contraction was slightly reduced by prazosin, but markedly reduced by scopolamine and NPY. The NPY effect was not influenced by pretreatment with rauwolscine. Pretreatment with NPY had no effect on contractions induced by noradrenaline (NA) or carbachol and the peptide did not relax preparations contracted by these agents. In circular muscle an initial, fast response, not sensitive to prazosin or scopolamine was occasionally observed following electrical stimulation. A slow contraction component was regularly seen; this response was abolished by prazosin. Neuropeptide Y did not influence any of these responses. The preparations were concentration-dependently contracted by NA, whereas carbachol had no effect. Pretreatment with NPY did not affect contractions induced by NA, nor did the peptide relax NA-contracted preparations. In neither longitudinal nor circular muscle strips did NPY affect the electrically induced TTX sensitive relaxation of NA-contracted preparations. The results suggest that in the rabbit urethra NPY reduces contractions in the longitudinal muscle layer by selectively inhibiting the release of acetylcholine from cholinergic nerves. Neuropeptide Y did not appear to have any significant postjunctional effects nor to interfere with the release, or effects of NA or other transmitter agents. The physiological importance of the urethral effects of NPY remains to be established.

Sex differences in function and distribution of alpha 1- and alpha 2-adrenoceptors in rabbit urethra.

To define the functional role of postsynaptic alpha-adrenoceptors in urethral smooth muscle, we examined the effects of various alpha-adrenergic agonists and antagonists on the contractile properties of the isolated urethra of male and female rabbits and quantified the population of alpha 1-and alpha 2-adrenoceptors, using radioligand receptor binding techniques. Norepinephrine (NE), epinephrine, and phenylephrine, an alpha 1-adrenergic agonist, induced increases in contractile force in both the male and female urethra. Clonidine, an alpha 2-adrenergic agonist, caused a relatively large contractile response in the female urethra but only a small contractile response in the male urethra. Receptor binding studies indicated that the male urethra contains almost equal amounts of alpha 1- and alpha 2-adrenoceptors (32 vs. 34 fmol/mg, respectively), whereas the female urethra contains a significantly greater density of alpha 2- than alpha 1-adrenoceptors (122 vs. 34 fmol/mg, respectively). Our studies indicate that both alpha 1- and alpha 2-adrenoceptors cause contractile responses in male and female rabbit urethra; and the greater response to alpha 2-agonist in female than male urethra is correlated with a higher density of alpha 2-adrenoceptors in this tissue.

Ketanserin Interaction with Urethral Alpha-Adrenoceptors

The selective 5-HT2 receptor blocker ketanserin was found to reduce maximal urethral pressures in healthy females by about 40% without reducing blood pressure. In vitro, ketanserin completely or almost completely reduced contractions of the isolated female rabbit urethra induced by phenylephrine, noradrenaline (NA) and electrical field stimulation. The drug was less effective against responses evoked by Clonidine and 5-hydroxytryptamine (5-HT). 5-HT-induced contractions were effectively reduced by methysergide, but little affected by prazosin and rauwolscine. In concentrations exceeding 10−7 M ketanserin significantly increased efflux of 3H in 3H-NA preloaded preparations of rabbit urethral muscle. Low concentrations of 5-HT, 10−6 M, had slight inhibitory effects of 3H release, whereas 5-HT 10−5 M caused a significant increase. It is concluded that ketanserin counteracts the effects of postjunctional α1-adrenoceptor stimulation in isolated rabbit urethra. Such an effect might also explain its urethral pressure lowering action in man.

Increases in Blood Flow of the Female Rabbit Urethra Following Low Dose Estrogens

The effects of low doses (0.05 to 20μg./kg.) of estradiol-17β (E2) and estriol (E3) on blood perfusion in the genitourinary tissues were examined two and 24 hours after an intra-arterial injection into rabbits. Whereas 0.05μg./kg. E2 or E3 caused no detectable change, 0.5μg./kg. of either E2 or E3 markedly increased blood flow measured after two hours in urethra, vagina and uterus. No significant increase in the blood flow in the urinary bladder or the ureters was observed. With 20μg./kg. E2 or E3 a much greater increase (10 to 25-fold) in the blood flow in the urethra, vagina and uterus was observed after two hours. At this time a small increase (about two-fold) could also be measured in urinary bladder and ureters. Twenty-four hours after this treatment (20μg./kg. E2 or E3), the blood flow in the urinary organs was not significantly different from the pretreatment values but it was still significantly elevated in uterus and vagina. These data show that the blood flow in the female urethra is just as sensitive to low doses of estrogens as uterus and vagina. Both E2 and E3 seem to be equally effective in increasing blood perfusion in the urogenital tissues.

α1- and α2-adrenoceptors in the smooth muscle of mal and female rabbit urethra

[ 3H]Prazosin and [ 3H]rauwolscine, specific α 1- and α 2-antagonists respectively, were used to label α-adrenoceptors in membranes from male and female rabbit uretra. In the male rabbit, [ 3H]prazosin bound with high affinity (K d = 0.56 nM) to a single population of sites with a capacity of 73 fmol/mg protein. [ 3H]Rauwolscine bound with a lower affinity (K d = 2.24 nM) to another single class of sites with a capacity of 41 fmol/mg protein. The order of potencies of various adrenergic compounds in inhibiting radioligand binding suggested that [ 3H]prazosin and [ 3H]rauwolscine interacted in the urethra with sites having the characteristics of α 1- and α 2-adrenoceptors, respectively. In addition, studies on the female rabbit urethra showed that α 2-adrenoceptor density and affinity were respectively 6 times higher and 2 times lower than in the male. No significant sex difference was observed for urethral α 1-adrenoceptors.

Regional distribution of alpha-adrenoceptor subtypes in the female rabbit urethra.

The aim of the present investigation was to study the regional distribution of alpha-adrenoceptor subtypes in the female rabbit bladder base and urethra, using radioligand binding and mechanical activity studies. The binding studies performed on membranes prepared from the bladder base, and the proximal and distal part of the urethra, revealed that the number of alpha 1-adrenoceptors did not significantly differ between the three regions, whereas the number of alpha 2-adrenoceptors increased distally. The mechanical activity studies showed that noradrenaline and clonidine, but not phenylephrine, were more potent in the distal than the proximal part of the urethra. It is suggested that in the female rabbit urethra the lower EC50-value found for noradrenaline and clonidine in the distal as compared to the proximal part of the urethra, at least in part, is attributable to a higher number of postjunctional alpha 2-adrenoceptors in the distal than in the proximal urethra.

Effects of neuropeptide Y on isolated preparations of the longitudinal and circular smooth muscle layers of the female rabbit urethra

Effects of neuropeptide Y on isolated preparations of the longitudinal and circular smooth muscle layers of the female rabbit urethra

Contractant and Relaxant Properties of the Female Rabbit Urethral Submucosa

Isolated submucosal (lamina propria) preparations from the female rabbit urethra exhibited both contractant and relaxant properties. The nerve-mediated contraction to electrical field stimulation was adrenergic in nature, and both this response and the contraction induced by exogenous application of noradrenaline were blocked to a greater extent by α2 than by α1-adrenoceptor blocking agents. Vasoactive intestinal polypeptide was found to be a potent inhibitor of the noradrenaline-mediated contraction. Neuropeptide Y induced contraction of the preparation, but also inhibited the nerve-mediated contractant response. In noradrenaline-contracted preparations, electrical field stimulation induced a non-adrenergic, non-cholinergic relaxation. The maximum relaxant response was significantly greater when the preparations were contracted by clonidine than by noradrenaline.Abundant smooth muscle cells with no obvious connection to vessel walls were found in the submucosa, but to what extent the contractant and relaxant responses can be ascribed to vascular or non-vascular smooth muscle is not settled.The results indicate a non-uniform distribution of the peripheral nervous control within the wall of the female rabbit urethra. The demonstrated contractant and relaxant properties of the submucosal tissue might be of importance for urethral function.

Differential effects of nifedipine, verapamil, and diltiazem on noradrenaline-induced contractions, adrenergic transmitter release, and alpha-adrenoceptor binding in the female rabbit urethra.

In order to study differences in action between "Ca2+-entry blockers" on smooth muscle and peripheral nerves, the effects of nifedipine, verapamil, and diltiazem on noradrenaline (NA)-induced contractions and electrically evoked release of 3H-NA were investigated in the female rabbit urethra. In addition, possible influences of Ca2+-entry blockers on alpha-adrenoceptors were studied with radioligand binding technique. Exposure to Ca2+-free medium completely abolished the contractile response to 1 microM NA in the rabbit urethra, indicating that the contraction was entirely dependent on influx of extracellular Ca2+. The Ca2+-entry blockers inhibited the NA-induced contractions in the following order of potency: nifedipine greater than verapamil approximately equal to diltiazem. In contrast to nifedipine and diltiazem, which produced a maximum inhibition of between 50 and 60%, verapamil was able to abolish the contractile responses to NA. The electrically evoked efflux of 3H-NA was decreased by diltiazem and increased by verapamil, whereas nifedipine failed to alter the 3H-NA efflux. Only verapamil was effective in inhibiting specific 3H-DHE binding to a crude membrane preparation of the rabbit bladder base and urethra, and the inhibition appeared to be of the competitive type. It is suggested that the effects of verapamil on electrically evoked efflux of 3H-NA and on NA-induced contractions can be partly explained by blockade of pre- and post-junctional alpha-adrenoceptors. The failure of nifedipine and diltiazem to abolish the NA-induced contraction might indicate the existence of different Ca2+-entry pathways in urethral smooth muscle.

Influence of antimuscarinics on alpha-adrenoceptors in the female rabbit urethra.

The effects of the tertiary amine atropine and its structural analogues homatropine and scopolamine, as well as the quarternary amine emeprone, were evaluated on noradrenaline (NA)-induced contractions of isolated female rabbit urethral ring preparations. In addition, the abilities of these antimuscarinics to inhibit 3H-dihydro-alpha-ergocryptine (3H-DHE) binding to alpha-adrenoceptors were studied on a crude membrane preparation from the female rabbit bladder base and urethra. Atropine and homatropine depressed the NA-induced contractions in a concentration-dependent way, whereas this was not seen with scopolamine. Emeprone 10(-5) and 10(-4) M augmented the contractions, an effect possibly attributable to a NA-uptake blocking effect. All antimuscarinics displaced specific 3H-DHE binding, the order of potency being atropine greater than homatropine greater than emeprone greater than scopolamine. In general a good correlation was seen between the binding and mechanical activity studies for atropine, homatropine and scopolamine, while this was not found for emeprone. It is concluded that alpha-adrenoceptor blockade by atropine can be observed at concentrations exceeding 10(-7) M. Scopolamine, showing alpha-adrenoceptor blocking properties only in high concentrations, may be used as an alternative for blockade of muscarinic cholinoceptors.

Characterization of the alpha-adrenoceptors in the female rabbit urethra.

A radioligand binding technique was used to evaluate the proportions of alpha 1- and alpha 2-adrenoceptors in crude membrane preparations obtained from the female rabbit bladder base and urethra. In addition, urethral rings were studied in vitro in an attempt to determine if alpha 1- and/or alpha 2-adrenoceptors are located postjunctionally in the urethral smooth muscle. Studies of the inhibition of [3H]-dihydroergocryptine binding by the selective alpha 1-adrenoceptor antagonist prazosin or the selective alpha 2-adrenoceptor antagonist rauwolscine revealed the alpha-adrenoceptor population to consist of approximately 25% alpha 1-adrenoceptors and 75% alpha 2-adrenoceptors. These proportions were confirmed in saturation studies with [3H]-prazosin and [3H]-rauwolscine. The sum of alpha 1- and alpha 2-adrenoceptors labelled by these selective alpha 1- and alpha 2-adrenoceptor antagonists was about equal to the number labelled by the non-selective alpha-adrenoceptor antagonist [3H]-dihydroergocryptine. Noradrenaline, as well as the selective alpha 1-adrenoceptor agonist phenylephrine and the selective alpha 2-adrenoceptor agonist clonidine, induced contractions of urethral ring preparations. Prazosin blocked contractions induced by phenylephrine to a greater extent than contractions induced by clonidine. The opposite was true for the inhibitory effect of rauwolscine. In addition to showing that both alpha 1- and alpha 2-adrenoceptor binding sites exist in membrane preparations of the rabbit bladder base and urethra, the results reveal the presence of both adrenoceptor subtypes postjunctionally in the rabbit urethra; and both mediate contraction of the smooth muscle.

Female Urethra: A Target for Estrogen Action

It is not uncommon to use estrogen therapy in patients with urinary stress incontinence. The possibility of a selective action of estrogen in the lower urinary tract was examined.Wet weight of the uterus, vagina and urethra increased significantly, and that of the urinary bladder insignificantly after estradiol treatment of ovariectomized rabbits. When ovariectomized rabbits were injected i.v. with 3H-estradiol, the tritium concentration, determined after 1 hour, was 3 to 4 times higher in urethra, urinary bladder and vagina than that in the muscle. High affinity estradiol receptors (KD∼1 X 10−9 M) could be demonstrated in both the cytoplasmic and nuclear fractions prepared from the female rabbit urethra and bladder. The concentrations of estradiol receptors in the urethra and bladder were about 10 and 20 times lower respectively than those in the uterus. The present evidence for estradiol receptors in the lower urinary tract supports the case for estradiol therapy in urinary incontinence.