Estrogen and postnatal maturation increase caveolar number and caveolin-1 protein in bladder smooth muscle cells

Clinical studies indicate that detrusor contractility decreases in old age and the dense band pattern with caveolar depletion represents the ultrastructural norm of the aged human detrusor. We performed animal studies to explore the hypothesis that lowering estrogen induces the dense band pattern with estrogen replacement restoring usual sarcolemmal appearance and increasing caveolar number.

Newborn, young (1-month-old) and middle-aged (13 to 14-month-old) female rats were studied. Middle-aged animals were evaluated 4 months after sham operation or ovariectomy (OVx) with OVx rats receiving placebo or 25% 17beta-estradiol (E2) capsules for 1 week prior to sacrifice. Electron microscopy was used to evaluate sarcolemmal structure and quantify caveolar numbers in bladder muscle cells. Caveolae were also assessed by measuring caveolin-1 protein.

Alternating electron dense and thinner zones with abundant caveolae were present in bladder sarcolemma from middle-aged animals. Newborn and OVx sarcolemma showed many ultrastructural features of the dense band pattern with fewer caveolae present per micro sarcolemma or per muscle cell compared with sham operated middle-aged controls. E2 replacement decreased the dense band pattern and increased caveolar numbers in OVx animals. Caveolin-1 protein levels underwent similar changes following maturation, OVx and E2 replacement, while alpha-smooth muscle actin remained unchanged.

Prolonged estrogen withdrawal results in sarcolemmal changes in middle-aged animals, similar to the dense pattern observed in newborns. Estrogen replacement decreases the dense pattern, while increasing caveolar numbers and caveolin-1 protein. It remains to be seen whether estrogen influences caveolar depletion and/or contractility in human bladders.