The long term goals of this proposal are to understand the molecular mechanisms that regulate growth and development of smooth muscle in the bladder wall, and to determine the influence of sex hormones on the expression of smooth muscle specific phenotypes. An understanding of the cell differentiation and the biochemical regulation of muscle contraction is important to elucidate the pathogenetic mechanism(s) responsible for the differences in urinary bladder function in males and females.
The specific aims of this proposal are two-fold: (a) to understand the biochemical mechanisms that regulate the actin-myosin interaction and contraction of the smooth muscle in the rabbit bladder wall during growth and development, and (b) to see if there are any differences between males and females in the expression of smooth muscle myosin in the bladder during growth. The urinary bladder is an estrogen-sensitive organ. Ovariectomy and estrogen treatment are known to alter micturition and bladder contractility. Furthermore, while there are no differences in these parameters in immature male and female rats, after sexual maturity significant differences are seen between males and females. Therefore, the developmental changes which occur at sexual maturity have significant effects on bladder function, and the mechanisms responsible for the differences in bladder function observed between the sexes should be defined. Using specific antibodies for immunocytochemistry and cDNA probes for in situ hybridization, we will be able to determine if smooth muscle cells in the rabbit bladder during growth express myosin heavy chain isoforms SM1 (204 kDa) and SM2 (200 kDa) in the same ratio as in smooth muscle cells from other sources. These studies will enable us to characterize the muscle cells in the urinary bladder with respect to their contractile apparatus to determine if sex hormones and sexual maturity have any effects on the contractility of the bladder smooth muscle. This information will enable us to elucidate the pathogenetic mechanism(s) and pathophysiology associated with bladder disorders in females.
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