Mapping of androgen, estrogen and progesterone receptors in the anal continence organ

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Abstract

Objective: To investigate the expression of androgen, estrogen and progesterone receptors (ARs, ERs, PRs) in the tissues of the anal continence organ using immunohistochemical techniques. Study design: Thirty-nine samples of anorectal tissue were obtained from 23 patients (seven men, seven premenopausal women and nine postmenopausal women). Immunostaining for ARs, ERs and PRs was performed by the ABC technique using 3,3′-diaminobenzidine tetrahydrochloride as the chromogen. Results: Specific immunostaining for ARs, ERs and PRs was found exclusively over cell nuclei. ARs were found in the smooth muscle cells of the internal anal sphincter in all but one of the females (10/11) and all males (7/7), ERs were found in 12/12 females and 4/7 males, and PRs were found in 4/10 females and 1/7 males. The squamous epithelium exhibited a similar pattern of immunostaining. The nuclei of the striated muscle fibers expressed none of the sex steroid receptors investigated. Conclusion: The intense expression of ARs, ERs and, in some cases, PRs in the tissues of the anal continence organ at all ages and in both sexes indicates that this organ is a target for sex steroid hormones.

Introduction

Urinary and fecal incontinence are problems that increase in incidence and severity with age and have a much higher prevalence in women than in men 1, 2. As both estrogen and progesterone receptors have been demonstrated in the tissues of the female urinary tract, the postmenopausal decline in estrogen and progesterone levels is thought to be involved in the development of urinary incontinence 3, 4, 5, 6.

Anorectal manometric studies have demonstrated lower anal squeeze pressures in elderly women than in younger females or age-matched men 2, 7. In this study, we attempted to establish the anatomic and pathophysiological basis for the increase in incidence of fecal incontinence in women with age, apart from direct obstetric damage of the anal sphincter. Using immunohistochemical techniques, we determined the distribution of androgen, estrogen and progesterone receptors (ARs, ERs, PRs) in the tissues of the anal continence organ in both sexes. On the basis of these results, the possible roles of age and sex in the development of fecal incontinence are discussed, and suggestions concerning possible effects of hormone replacement therapy are formulated.

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Materials and methods

Thirty-nine samples of anorectal tissue were obtained from 23 patients (seven men, seven premenopausal women and nine postmenopausal women). The specimens were obtained at abdominoperineal resection for neoplasia in eleven cases, at hemorrhoidectomy in ten cases, at anal fissure resection in one case, and at proctoperineorrhaphy after sphincter injury in one case (Table 1). After fixation in 4% formalin for 16–20 h, the tissue samples were dehydrated and embedded in paraffin. Serial sections (5

Tissues and immunostaining for ARs, ERs and PRs

The results of the immunohistochemical staining procedures are summarized in Table 1. As the tissue specimens were taken from different anatomical sites, they usually did not contain all of the tissue compartments of interest. Assessable amounts of stratified squamous anal epithelium and of the smooth muscle tissue of the internal anal sphincter were available in 19 of the 23 cases, whereas columnar rectal epithelium and striated muscle of the external anal sphincter were present in eight and

Expression of sex steroid receptors in the anal continence organ

The essential finding of this study is that most of the tissues of the anal continence organ express receptors for androgens, estrogens and, sometimes, gestagens. These sex hormone receptors are expressed in a well-defined anatomical pattern, which is essentially identical in both sexes. This pattern remained unchanged throughout the range of adult life investigated (19–82 years; Table 1). Fig. 2 summarizes the distribution of these receptors. The stratified squamous epithelium of the anal

Conclusion

The intense expression of ARs, ERs and, sometimes, PRs in the tissues of the anal continence organ at all ages and in both sexes indicates that this organ is a target for steroid sex hormones. We assume that these hormones have trophic and functionally stimulating effects on the anal continence organ that are transmitted via these receptors. We suggest that, as shown by a very recent study [14], prolonged hormone replacement therapy may have a beneficial effect on anal continence. In addition,

Acknowledgements

We wish to thank Mrs. Gabriele Haug for excellent technical assistance. We are also grateful to Mrs. M. Keller and Mrs. R. Pompe for secretarial assistance and Dr. Margaret Ruck for help in translation of the manuscript.

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