Effects of Ovarian Steroids on Vaginal Smears in the Rat

Montes, G. S.; Luque, Enrique H.

doi:10.1159/000146639

Cited by 159 publications

(91 citation statements)

References 11 publications

(1 reference statement)

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“…Rats that exhibited at least 7 days of atrophic vaginal smears (Montes & Luque 1988) were injected s.c. daily for 4 days with vehicle (sesame oil), E 2 (0·05 or 5 µg/rat), P 4 (1 mg/rat) or a combination of both steroids. Rats were included in one of six experimental groups (n=7-8 rats/group): sesame oil (control), low dose of E 2 (0·05 E), high dose of E 2 (5 E), P 4 (P) or combinations 0·05 E+P and 5 E+P.…”

Section: Experimental Designmentioning

confidence: 99%

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The estrogen receptor α Σ3 mRNA splicing variant is differentially regulated by estrogen and progesterone in the rat uterus

Varayoud¹,

Ramos²,

Monje³

et al. 2005

Journal of Endocrinology

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The gene for estrogen receptor (ER ) has been shown to be under complex hormonal control and its activity can be regulated by mRNA alternative splicing. Here we examined the regulation of ER transcription and translation in the rat uterus by ovarian steroid hormones. We examined whether expression of ER mRNA splice isoforms is hormonally regulated in ovariectomized (OVX) and cycling rats. Adult OVX female rats were treated daily with 17-estradiol (E 2 ) (0·05 µg/rat or 5 µg/rat), progesterone (P 4 ) (1 mg/rat) or a combination of both hormones for 4 days. Animals were killed 24 h after the last injection and uterine horns were removed. In order to determine whether ER mRNA isoforms are differentially expressed under various physiological conditions, animals were evaluated at proestrus, estrus and diestrus. The ER protein and mRNA were detected by immunohistochemistry and comparative RT-PCR analysis respectively. The presence of ER mRNA isoforms was evaluated using a nested RT-PCR assay. In OVX control rats, ER mRNA and protein levels were high, demonstrating a constitutive expression of the ER gene in the uterus. When animals received P 4 or the high dose of E 2 , a significant decrease in both ER mRNA and protein was observed in the uterus. However, when rats were treated with the low dose of E 2 , only the ER protein was down-regulated; no changes were observed in ER mRNA expression. In addition to the full-length ER mRNA, OVX control rat uteri expressed three shorter transcripts: 3, 4 and 3,4 (lacking exon 3, exon 4, or both 3 and 4 respectively). Surprisingly, when OVX animals were treated with P 4 , the low dose of E 2 or a combination of both steroids, expression of the 3 isoform was completely abolished. During the estrous cycle, all ER mRNA splicing variants were detected at proestrus and estrus. However, in diestrus, significant low levels of the 3 isoform were observed. In summary, our results suggest a dose-dependent relationship between E 2 concentrations and the level of control in the ER transcription-translation cascade. Moreover, the alternative splicing of the ER primary transcript is influenced by the hormonal milieu, suggesting that these events could affect the estrogen responsiveness of the rat uterus during the estrous cycle.

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Section: Experimental Designmentioning

confidence: 99%

“…Daily vaginal cytology was examined to establish different stages of the estrous cycle (Montes & Luque 1988). Only rats exhibiting three consecutive regular estrous cycles were employed.…”

Section: Experimental Designmentioning

confidence: 99%

The estrogen receptor α Σ3 mRNA splicing variant is differentially regulated by estrogen and progesterone in the rat uterus

Varayoud¹,

Ramos²,

Monje³

et al. 2005

Journal of Endocrinology

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“…OV mice presented only the diestrus pattern while in Sham mice the four stages of the estrous cycle (proestrus, estrus, metestrus, and diestrus) were clearly verified (22). Five days after surgery, all animals were placed on an atherogenic high fat and high cholesterol (HFHC) diet containing 15% fat, 1.25% cholesterol, and 0.5% cholic acid (Cat.…”

Section: Animal Proceduresmentioning

confidence: 99%

Cholesteryl ester transfer protein expression attenuates atherosclerosis in ovariectomized mice

Cazita

Berti

Aoki

et al. 2003

Journal of Lipid Research

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(2); however, the precise effects of CETP on atherogenesis are controversial. In humans, increased incidence of coronary heart disease has been associated with both CETP deficiency (3) and augmentation (4). In several animal models of atherosclerosis, the effects of CETP on vascular health are clearly dependent upon the metabolic context (5-11).Various researchers are attempting to target CETP as a form of therapy (9-13), but these approaches will be useless unless the circumstances where CETP acts as pro-or anti-atherogenic are properly clarified.Deficiency in endogenous estrogen accounts for the loss of protection against coronary heart disease after menopause or following bilateral ovariectomy (14). Estrogen deficiency per se does not alter plasma CETP activity as shown in castrated CETP transgenic mice (15). Also, estrogen therapy has no impact on the plasma CETP activity in humans (16) as well as in apolipoprotein B/CETP double transgenic mouse model (17).The present study aimed at investigating whether CETP expression would alter the development of atherosclerosis in a moderately hypercholesterolemic mouse model lacking ovarian hormones. For this purpose, mice expressing the human CETP gene were crossbred with LDL receptor (LDLR) knockout mice. On a high fat diet, the LDLR knockout mice develop extensive aorta atherosclerosis in a pattern similar to humans (18,19). We have shown here that the expression of the CETP gene significantly reduced the development of atherosclerotic lesions in ovariectomized hypercholesterolemic mice. Furthermore, this antiatherogenic effect of CETP was blunted by the estrogen replacement therapy.

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“…To obtain pregnant specimens, proestrous females were caged overnight with males with proven fertility. Pregnancy was confirmed by the presence of spermatozoa in the vaginal smear the morning after coitus, defined as day 1 of pregnancy (D1; Freeman 1988, Montes & Luque 1988. In this colony, delivery occurred on D23.…”

Section: Animalsmentioning

confidence: 99%

Mast cell degranulation in rat uterine cervix during pregnancy correlates with expression of vascular endothelial growth factor mRNA and angiogenesis

Bosquiazzo¹,

Ramos²,

Varayoud³

et al. 2007

Reproduction

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Vascular growth of the uterine cervix during pregnancy is associated with mast cell (MC) degranulation. To better understand the mechanism underlying this process, uterine cervices of intact pregnant rats were dissected and endothelial cell proliferation was measured by a bromodeoxyuridine incorporation technique. Total vascular endothelial growth factor (VEGF) mRNA expression and the relative abundance of VEGF splice variants (120, 164, and 188) were determined by RT-PCR. VEGF protein expression was evaluated by immunohistochemistry. To investigate the role of MCs on cervical angiogenesis, a second set of pregnant animals were treated with an MC stabilizer (disodium cromoglycate) to inhibit MC degranulation. Furthermore, 17b-estradiol (E 2 ) serum levels were established by RIA. In intact pregnant rats, VEGF mRNA expression was positively correlated with endothelial cell proliferation and circulating E 2 levels. All selected splice variants of VEGF gene were detected and their relative abundance did not show any change throughout pregnancy. Animals treated with disodium cromoglycate showed a decrease in endothelial cell proliferation and in VEGF mRNA expression compared with controls. Relative abundance of VEGF mRNA splice variants and E 2 serum levels showed no differences between these experimental groups. These results show a time-dependent correlation between VEGF mRNA expression and E 2 serum levels in the uterine cervix of intact pregnant rats, while MC stabilizer-treated animals reduced the VEGF expression without modifying E 2 serum levels. We suggest that cervical angiogenesis during pregnancy could be regulated by a mechanism which involves endogenous E 2 and chemical mediators stored in MC granules via a VEGFdependent pathway.

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Effects of Ovarian Steroids on Vaginal Smears in the Rat

Cited by 159 publications

References 11 publications

The estrogen receptor α Σ3 mRNA splicing variant is differentially regulated by estrogen and progesterone in the rat uterus

The estrogen receptor α Σ3 mRNA splicing variant is differentially regulated by estrogen and progesterone in the rat uterus

Cholesteryl ester transfer protein expression attenuates atherosclerosis in ovariectomized mice

Mast cell degranulation in rat uterine cervix during pregnancy correlates with expression of vascular endothelial growth factor mRNA and angiogenesis

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