Effect of Estrogens on the Weight and Muscarinic Cholinergic Receptor Density of the Rabbit Bladder and Urethra

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Abstract
We have determined the muscarinic cholinergic receptor (MChR) density in the adult female rabbit bladder body and bladder base/urethra following three weeks of estrogen treatment. Fifteen female rabbits were separated into three treatment groups. Group I remained intact, Group II underwent bilateral ovariectomy, and Group III underwent simultaneous bilateral ovariectomy followed by subcutaneous placement of a 250 mg. estradiol pellet. The weight, total DNA content, and MChR density were determined for each of the tissues in the three treatment groups. The mean weight of the bladder body following ovariectomy and estrogen treatment (Group III) was threefold greater than in the intact rabbits (Group I) (p <0.001) and two-fold greater than in the ovariectomized rabbits (Group II) (p <0.05). Similar increases were observed in the mean weights of the bladder base/urethral segments in the three treatment groups. The mean total DNA content in Group III was also significantly greater than Group I (p <0.01) and Group II (p <0.05) for both the bladder body and bladder base/urethral segment. The MChR density in the three treatment groups was determined using radioligand receptor binding using [3H]N-methylscopolamine ([3H]NMS). The MChR density in the bladder body (1.72 fmol./gm. DNA) for Group III was significantly decreased compared to the receptor density in both Group I (3.17 fmol./gm. DNA) and Group II (3.14 fmol./gm. DNA) (p <0.05). The binding of [3H] NMS to the MChR in bladder body was of high affinity (Kd = 0.07-0.15 nM) and was unaltered by hormonal treatment. No difference was found in the MChR density in the bladder base/urethral segment in any of the three treatment groups. In this study, we have shown that estrogens increase the weight and modulate the MChR density of the female rabbit bladder body. The ability to modulate neurotransmitter receptor density by sex steroid hormones may have important clinical implications.