Korean J Urol.  2006 Jan;47(1):55-63. 10.4111/kju.2006.47.1.55.

The Effects of Estrogen on Neuronal Nitric Oxide Synthase Expression, Endothelial Nitric Oxide Synthase Expression and Vascular Endothelial Growth Factor Expression and on the Histologic Composition of Rat Uterus and Vagina

• Park SW
• Lee YJ
• Lee JZ

• KMID: 2294216
• DOI: http://doi.org/10.4111/kju.2006.47.1.55

Abstract

PURPOSE: As suggested by many investigators, the cause of age-related female sexual dysfunction is the decline of serum estrogen. We investigated the effects of estrogen on the nitric oxide synthase (NOS) and vascular endothelial growth factor (VEGF) expressions and the histologic composition in the uterus and proximal and distal vagina of rats.
MATERIALS AND METHODS
Forty-five mature female Sprague-Dawley rats were randomly divided into three groups; the control group (C), the oophorectomy group (O), and the estrogen replacement group (E). The expression rates of neuronal NOS (nNOS), endothelial NOS (eNOS), VEGF and the changes of the collagen component in the uterus and proximal and distal vaginal tissues were investigated by immunohistochemical staining and Masson's trichrom staining.
RESULTS
The expression rate of NOS was highest in the proximal vagina, and this was followed by the portion of the vagina distal to the uterus. The nNOS and eNOS expression rates were significantly decreased in the uterus and the proximal vagina of the E group (p<0.05), and they were increased in the uterus and proximal vagina of the O group (p<0.05). However, the VEGF expression rate was increased in only the uterus of E group. In all tissues, the collagen component was significantly decreased in the E group, while it was increased in the O group (p<0.05).
CONCLUSIONS
These data suggest that estrogen downregulates nNOS and eNOS. In addition, estrogen deficiency induces collagen synthesis and it decreases the content of smooth muscle in the uterus and vagina, resulting in structural relaxation difficulty.

Keyword

Nitricoxide synthase; Vascular endothelial growth factor; Sexual dysfunctions; Estrogens

MeSH Terms

Animals
Collagen
Estrogen Replacement Therapy
Estrogens*
Female
Humans
Muscle, Smooth
Neurons*
Nitric Oxide Synthase
Nitric Oxide Synthase Type I*
Nitric Oxide Synthase Type III*
Ovariectomy
Rats*
Rats, Sprague-Dawley
Relaxation
Research Personnel
Uterus*
Vagina*
Vascular Endothelial Growth Factor A*
Collagen
Estrogens
Nitric Oxide Synthase
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type III
Vascular Endothelial Growth Factor A

Figure

• 

  Fig. 1 The mean serum 17β-estradiol. *: p-value (comparing the control group with the oophorectomy group)<0.001, †: p-value (comparing the oophorectomy group with the estrogen replaced group)<0.001.

• 

  Fig. 2 The mean expression percentage. (A) nNOS, (B) eNOS, (C) VEGF, (D) relative percentage of the collagen component, *: p-value (comparing the control group with the oophorectomy group)<0.05, †: p-value (comparing the oophorectomy group with the estrogen replaced group)<0.05. nNOS: neuronal nitric oxide synthase, eNOS: endothelial nitric oxide synthase, VEGF: vascular endothelial growth factor.

• 

  Fig. 3 Immunoreactivity pattern for neuronal nitric oxide synthase (nNOS) of rat uterus, the proximal vagina and the distal vagina. (A) nNOS expression in the uterus (×200, O: O group, E: E group), (B) the proximal vagina (×200, O: O group, E: E group), (C) the distal vagina (×200, O: O group, E: E group).

• 

  Fig. 4 Immunoreactivity pattern for endothelial nitric oxide synthase (eNOS) of rat uterus, the proximal vagina and the distal vagina. (A) eNOS expression in the uterus (×200, O: O group, E: E group), (B) the proximal vagina (×200, O: O group, E: E group), (C) the distal vagina (×200, O: O group, E: E group).

• 

  Fig. 5 Immunoreactivity pattern for vascular endothelial growth factor (VEGF) of rat uterus, the proximal vagina and the distal vagina. (A) VEGF expression in the uterus (×200, O: O group, E: E group), (B) the proximal vagina (×200, O: O group, E: E group), (C) the distal vagina (×200, O: O group, E: E group).

• 

  Fig. 6 Masson's trichrome stains of the uterus, proximal vagina, and distal vagina (×200). (A) collagen and smooth muscle component in the uterus (×200, O: O group, E: E group), (B) the proximal vagina (×200, O: O group, E: E group), (C) the distal vagina (×200, O: O group, E: E group).

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