Immunohistochemical investigations of estrogen receptors in normal and neoplastic squamous epithelium of the vulva

Atrophic disease of the vulvar epithelium can be treated with steroids, but carcinoma of the vulva cannot be influenced with any hormone therapy. Seventy-one vulvar specimens were tested for estrogen receptor (ER) content by means of immunohistochemistry. Slight ER staining was found in nonkeratinizing squamous epithelium in 17 of 22 cases. A weak ER reaction in the basal and parabasal layers was found in only 2 of 17 specimens of keratinizing squamous epithelium. However, no ER was found in any neoplastic tissue of the vulva or the adjacent stroma. The loss of ER in neoplastic cells could explain the clinical experience that antihormonal treatment of vulvar carcinomas produces no appreciable improvement.     

Immunohistochemical evidence of estrogen and progesterone receptors in the female lower urinary tract and comparison with the vagina.

Tissue biopsies from the lower urinary tract and the vagina were obtained from 51 and 45 women, respectively, during incontinence surgery or other gynecological operation procedures in order to calculate hormone receptor content. We compared the results between premenopausal, postmenopausal patients with and those without hormonal treatment. Utilizing the enzyme immunohistochemical assay we were able to demonstrate nuclear estrogen and progesterone receptors in the smooth muscle of the trigone and the posterior part of the bladder neck. But only in about 50% of the patients receptor proteins were detected in the frozen thin sections of these tissues. Biopsies from the anterior part of the bladder neck and the bladder vault were never receptor positive. In the vagina the rate of receptor-positive tissues was about 80%; in comparison, a smaller number of patients had receptor-positive cells in the bladder. From 29 patients we obtained specimens from the trigone and the vagina as well. The correlation of receptor-positive and -negative tissues of both organs was only 66%. Thus tissue biopsies obtained from the vagina only are not sufficient to discuss the probability of hormonal influence of the lower urinary tract.     

Resurfacing the vulva and vagina

Thirteen patients are described where split thickness skin grafts, cutaneous or myocutaneous flaps were used to cover large defects on the vulva and vagina. For defects over the pubic groin areas, the tensor fascia lata flaps are most suitable. Defects of the vulva are best covered by split thickness skin grafts or gracilis flaps, and vaginal defects by split thickness skin grafts or vulvar flaps.     

Lifetime changes in the vulva and vagina

The morphology and physiology of the vulva and vagina change over a lifetime. The most salient changes are linked to puberty, the menstrual cycle, pregnancy, and menopause. The cutaneous epithelia of the mons pubis, labia, and clitoris originate from the embryonic ectoderm and exhibit a keratinized, stratified structure similar to the skin at other sites. The mucosa of the vulvar vestibule, which originates from the embryonic endoderm, is non-keratinized. The vagina, derived from the embryonic mesoderm, is responsive to estrogen cycling. At birth, the vulva and vagina exhibit the effects of residual maternal estrogens. During puberty, the vulva and vagina acquire mature characteristics in a sequential fashion in response to adrenal and gonadal maturation. A trend to earlier pubertal onset has been observed in Western developed countries. In women of reproductive age, the vaginal mucosa responds to steroid hormone cycling, exhibiting maximal thickness and intracellular glycogen content at mid-cycle. Vulvar skin thickness remains unchanged but menstrual cycle-associated changes in ortho- and parakeratosis occur at the cytological level. The vulva and vagina further adapt to the needs of pregnancy and delivery. After menopause, tissue atrophy ensues. Post-menopausal changes in skin barrier function, skin hydration, and irritant susceptibility have been observed on exposed skin but not on the vulva. Nevertheless, older women with incontinence are at increased risk for developing incontinence dermatitis. A combination of factors, such as tissue atrophy, slower dissipation of excess skin hydration, shear forces associated with limited mobility, and lower tissue regeneration capacity increase the risk of morbidity from incontinence dermatitis in older women.     

An immunohistochemical study of androgen, oestrogen and progesterone receptors in the vulva and vagina

Objective Tomap potential sites of sex steroid action in the human vulva.
Methods Monoclonal antibodies to androgen, oestrogen and progesterone receptors were used to stainfrozen sections of vulval skin, vagina and suprapubic skin. A scoring system was devised to comparereceptor distribution in the epidermis and dermis of skin with vaginal epithelium and stroma.
Results Androgen receptors were seen in epidermal keratinocytes, sebaceous glands, sweat glands, hairfollicles and dermal fibroblasts of skin, and epithelial cells and stromal fibroblasts of the vagina. Androgen receptor scores were significantly higher in the epidermis of labia majora and minora thanin vaginal epithelium. Oestrogen receptors were seen in basal and suprabasal cells of vaginalepithelium and epidermis of labia minora but were restricted to basal keratinocytes in true skin.They were seen in stromal fibroblasts and vaginal smooth muscle, and dermal fibroblasts of theskin. Oestrogen receptors were highest in vaginal epithelium and stroma, and lowest insuprapubic skin. Progesterone receptors were seen in vaginal epithelium, fibroblasts and smoothmuscle but not in the vulva. There was no evidence of significant differences in androgen oroestrogen receptor staining in the vulva of pre- or postmenopausal women.
Conclusion The transition from vagina to vulva is marked by an increase in androgen and a decrease inoestrogen and progesterone receptors. This distribution of receptors would indicate a limited role foroestrogen creams on the vulva.     

Immunohistochemical detection of estrogen and progesterone receptors in endometriotic tissue

30 formalin-fixed and paraffin embedded and 20 fresh frozen samples of endometriotic tissue were analysed immunohistochemically for the concentration of estrogen and progesterone receptors. In the formalin-fixed and paraffin embedded group only 37% of the samples were estrogen receptor positive whereas 63% were receptor negative. In contrast, we found that 67% of the samples had a positive progesterone receptor status. In the fresh frozen group 60% of endometriotic tissues were estrogen receptor positive and 75% of the tissues had a positive progesterone receptor status. We could not find any correlation between the site or severity of the endometriosis or the hormonal receptor status. We were able to demonstrate that the immunohistochemical detection of hormonal receptors in endometriotic tissues is possible and that better results were obtained if fresh frozen rather than formalin-fixed and paraffin embedded tissues were analyzed.     

Sarcoma of vulva, vagina and ovary

Less than 5% of vulvar, vaginal and ovarian malignant diseases are sarcomas. Adequate knowledge of these particular malignant diseases is essential for accurate diagnosis and for choice of surgical treatment, adjuvant therapy and efficient medical treatment in relapse. A crucial aspect in the management of women with these diseases is a multidisciplinary approach. Globally, presenting signs and symptoms of these sarcomas are non-specific of histological type but linked to initial location. In view of this, management should be undertaken by clinicians experienced in these particular malignancies. Long-term side-effects, particularly in children with sarcoma, adversely affect quality of life. New treatment strategies require special attention.     

Testosterone increases blood flow and expression of androgen and estrogen receptors in the rat vagina

IntroductionThe mechanisms by which testosterone modulates female genital sexual arousal responses are poorly understood.AimTo investigate the effects of testosterone on vaginal blood flow and the expression of estrogen and androgen receptor proteins in the rat vagina.MethodsMature female Sprague-Dawley rats were sham-operated (intact) or ovariectomized. Fourteen days after ovariectomy, animals were continuously infused with vehicle or varying doses of testosterone (5.5–55 μg/day). After 2 weeks of treatment, vaginal blood flow in response to pelvic nerve stimulation was measured by laser Doppler flowmetry. Plasma levels of testosterone and estradiol were determined by radioimmunoassay and epithelial thickness was examined in fixed vaginal tissue sections. Androgen and estrogen receptor levels were assessed by equilibrium radioligand binding and by Western blot analyses.ResultsVaginal blood flow responses were significantly reduced in ovariectomized rats and normalized in animals infused with testosterone. Ovariectomy increased the expression of estrogen receptors and reduced the expression of androgen receptors with no change in receptor-ligand affinity. Testosterone increased the expression of both androgen and estrogen receptors in the vagina. While physiological (11 μg/day) and supraphysiological (55 μg/day) concentrations of testosterone normalized vaginal tissue weight, uterine tissue and whole body weights were not significantly different from ovariectomized rats infused with vehicle. Testosterone infusion, even at supraphysiological concentrations, did not change plasma estradiol levels when compared to vehicle-infused, ovariectomized rats. Likewise, the vaginal epithelium of testosterone-infused rats remained atrophic, similar to vehicle-infused, ovariectomized rats, indicating that testosterone is not aromatized to estrogens at significant levels in the vagina.ConclusionsOur data suggest that testosterone regulates androgen and estrogen receptor protein expression in the vagina and enhances vaginal perfusion by an androgen-dependent mechanism. We conclude that testosterone plays an important role in modulating the physiology of the vagina and contributes to improvement of genital sexual arousal responses. Traish AM, Kim S Woong, Stankovic M, Goldstein I, and Kim NN. Testosterone increases blood flow and expression of androgen and estrogen receptors in the rat vagina.     

Immunohistochemical study of distribution of estrogen receptors in corpus and cervix uteri

Summary An immunohistochemical assay based on monoclonal antiestrophilin antibodies has been used to localize estrogen receptor (ER) in frozen sections of normal human endometrial, myometrial and cervical tissues from menstruating, hormonally treated, pregnant and postmenopausal women. Specific staining was confined to the cellular nuclei. In proliferative phase endometrium, postmenopausal emdometrium, and endometrium from patients treated with hormone ERs were easily detected in most glandular and stromal cells. After ovulation and in early pregnancy a quick and distinct decrease of ER expression was noted. This was especially the case with the more superficial layers of endometrium (endometrium functionals), the majority of whose cells had either weak localization of ER or none at all. In the endometrium basalis, however, the reduction of ER localization turned out to be more moderate. More then half of the epithelial and stromal cells displayed nuclear staining, partly strong. The myometrium of the corpus uteri showed a similar ER localization and dependence on hormonal stage when compared with the endometrium functionalis. The endocervical mucosa displayed a high degree of ER expression in the proliferative phase in postmenopausal women and in women who had been treated with hormones. Unlike the endometrium and myometrium, the endocervical glands underwent minimal changes in nuclear ER content during the menstrual cycle. Although the endocervical stroma showed cyclic alterations in ER levels, their reduction after ovulation was less marked than in the corresponding endometria. In cervical squamous epithelium ER localization was predominantly confined to the basal layers. In the course of cellular maturation, specific nuclear staining vanished. In the proliferative phase, after the menopause and in early pregnancy, the basal, parabasal and intermediate cells were specifically stained. In the postovulatory phase. However, nuclear staining was confined to the basal and parabasal cells. Hormonally treated squamous epithelia almost completely lacked nuclear ER localization.Dedicated to Professor V. Becker, Erlangen, on the occasion of his 65th anniversary