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

PURPOSE 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. MATERIALS AND METHODS 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. RESULTS 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. CONCLUSIONS 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.

[1]  B. Riggs,et al.  Estrogen and the Male Skeleton , 2002 .

[2]  N. Resnick,et al.  Role of ovarian hormones in the pathogenesis of impaired detrusor contractility: evidence in ovariectomized rodents. , 2001, The Journal of urology.

[3]  V. Miller,et al.  Temporal effects of 17β-estradiol on caveolin-1 mRNA and protein in bovine aortic endothelial cells , 2001 .

[4]  Michael P. Lisanti,et al.  Emerging Themes in Lipid Rafts and Caveolae , 2001, Cell.

[5]  T. Lue,et al.  The effect of simulated birth trauma and/or ovariectomy on rodent continence mechanism. Part I: functional and structural change. , 2001, The Journal of urology.

[6]  A. Wein,et al.  Estrogen modulates the expression of myosin heavy chain in detrusor smooth muscle. , 2001, American journal of physiology. Cell physiology.

[7]  N. Resnick,et al.  Can variability in the hormonal status of elderly women assist in the decision to administer estrogens? , 2001, Journal of women's health & gender-based medicine.

[8]  B. Katzenellenbogen,et al.  Caveolin-1 Potentiates Estrogen Receptor α (ERα) Signaling , 1999, The Journal of Biological Chemistry.

[9]  G. Dohanich,et al.  Effects of Ovarian Hormones and Environment on Radial Maze and Water Maze Performance of Female Rats , 1999, Physiology & Behavior.

[10]  J. Gaughan,et al.  Expression of oestrogen receptor beta (ER beta) in multiple rat tissues visualised by immunohistochemistry. , 1997, The Journal of endocrinology.

[11]  J. Thyberg,et al.  Expression of caveolae on the surface of rat arterial smooth muscle cells is dependent on the phenotypic state of the cells. , 1997, Laboratory investigation; a journal of technical methods and pathology.

[12]  N. Resnick,et al.  Structural basis of geriatric voiding dysfunction. II. Aging detrusor: normal versus impaired contractility. , 1993, The Journal of urology.

[13]  N. Resnick,et al.  The pathophysiology of urinary incontinence among institutionalized elderly persons. , 1989, The New England journal of medicine.

[14]  C. Hsu,et al.  Effect of estrogen on the expression of mRNAs of different actin isoforms in immature rat uterus. Cloning of alpha-smooth muscle actin message. , 1987, The Journal of biological chemistry.

[15]  H E Wichmann,et al.  [What is "normal"?]. , 1979, Die Medizinische Welt.

[16]  E. Levin,et al.  ERs associate with and regulate the production of caveolin: implications for signaling and cellular actions. , 2002, Molecular endocrinology.

[17]  S. Hayward,et al.  Ontogeny of the rat bladder: smooth muscle and epithelial differentiation. , 1996, Acta anatomica.

[18]  Takao Inoué The three-dimensional ultrastructure of intracellular organization of smooth muscle cells by scanning electron microscopy , 1990 .

[19]  Julie H. Campbell,et al.  Ultrastructure of smooth muscle cells in culture , 1990 .

[20]  H. Katabuchi,et al.  Ultrastructure of smooth muscle tissue in the female reproductive tract: uterus and oviduct , 1990 .

[21]  F. Karsch,et al.  Role of estrogen as initiator of daily LH surges in the ovariectomized rat. , 1975, Endocrinology.

[22]  A. Somlyo,et al.  Ultrastructure of Smooth Muscle , 1975 .