Effects of estrogen on nitric oxide synthase and histological composition in the rabbit clitoris and vagina

Abstract

We investigated the functional and histological changes after oophorectomy in the rabbit clitoris and vagina to determine the mechanism responsible for the development of arousal disorder in postmenopausal women. Twenty mature female New Zealand white rabbits were randomly divided into three groups: control; oophorectomy; and estrogen replacement after oophorectomy. We compared the nitric oxide synthase (NOS) activity and the degree of expression of neuronal (nNOS) and endothelial NOS (eNOS) using biochemical and Western blot analysis in clitoral and vaginal tissues. Histological change of smooth muscle and collagen contents in those tissues were also compared using Masson's trichrome staining. NOS activity and the expression of nNOS and eNOS were signi®cantly increased in the oophorectomized group while there was a decrease to the level of the control group in the estrogen replacement group. Histological examination showed that oophorectomy induced a signi®cant increase in collagen and decrease in muscle content in both clitoris and vagina, while the ratio of smooth muscle content was increased signi®cantly after the estrogen replacement. Our results clearly demonstrate that estrogen de®ciency induces compensatory NOS production which may be related to decreases in muscle to collagen ratio in female rabbit genital organs.

Sex steroid hormones differentially regulate nitric oxide synthase and arginase activities in the proximal and distal rabbit vagina

“…Yoon et al 30 have demonstrated increased clitoral and vaginal e-NOS and n-NOS protein expression and activity in ovariectomized rabbits, and expression and activity of NOS was reduced by estrogen administration. Since pelvic nerve-stimulated blood flow to the clitoris and vagina requires estrogen priming, 45 it remains unclear how changes in NOS expression and activity in response to estrogens correlate with blood flow in these genital organs.…”

“…23,[26][27][28][29][30]41,[44][45][46] Recent in vitro organ bath studies 44 have shown that EFS elicited NANC relaxation responses in the rabbit clitoral corpus cavernosum smooth muscle and these responses are inhibited with L-NAME and ODQ, suggesting a role for NO/cGMP pathway in clitoral physiology. Studies with rabbit vaginal strips in organ bath studies 47 have suggested that the NANC neurotransmitter does not involve NO.…”

“…We demonstrated that the NO/cGMPathway modulates pelvic nervemediated blood flow in the vagina. Furthermore, the activity of NOS has been shown to be modulated by estrogens [26][27][28][29][30] and androgens. [31][32][33][34] NOS activity may also be regulated by limiting the availability of the substrate L-arginine by the enzyme arginase, which metabolizes L-arginine to urea and orni-thine.…”

Relation of Sex Steroid Hormones to Genital Tissue Structure and Arousal: A Sampling of Manuscripts Discussing Endocrinologic Sexual Dysfunction

“…Several articles [1][2][3][4][5] concerning mechanistic studies in sex steroid hormones and sexual function/ dysfunction have been published recently in the IJIR: The Journal of Sexual Medicine, consistent with the contemporary nature of this physiological/ pathophysiological association. In 2001, Park et al 1 reported on three groups of female New Zealand White rabbits (control and bilateral oophorectomy with and without estrogen replacement).…”

“…Those animals in the oophorectomy group had significantly less genital blood flow and, histologically, had significantly less genital smooth muscle compared to the other groups, leading to the conclusion that estradiol played an important role in female genital structure and function. Also, in 2001, Yoon et al, 2 in similar groups of female rabbits, measured nitric oxide synthase (NOS) activity and expression of neural NOS and endothelial NOS using biochemical and Western blot analyses. They reported that oophorectomy significantly increased tissue NOS activity as well as eNOS and nNOS expression, concluding that the estrogen hormonal milieu influences female genital tissue structure and function.…”