The biological activity of a single dose of tamoxifen in the adult ovariectomized rat

Bowman, Susan; Jones, Christine Ann; Leake, A.; Morris, Ian D.

doi:10.1111/j.1476-5381.1983.tb09411.x

Cited by 10 publications

(6 citation statements)

References 20 publications

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“…However, the results are consistent with previous studies in which weight gain and food intake were suppressed in ovariectomized rats treated with tamoxifen by daily injections (Wade and Heller, 1993) or following a single administration (Bowman et al, 1983). In this respect, tamoxifen would appear to mimic estrogen.…”

Section: Discussionsupporting

confidence: 83%

“…Tamoxifen mimics the activity of estrogen and increases uterine weight in immature and ovariectomized adult rats (Bowman et al, 1983;Wakeling et al, 1991) but decreases uterine weight in intact adult rats (Wakeling and Bowler, 1988). The sustained decrease in uterus weight by tamoxifen noted in the current study is suggestive of antiestrogenic activity.…”

Section: Discussionsupporting

confidence: 53%

“…Support for a hormonal mechanism stems from reports that tamoxifen suppressed growth hormone (GH) secretion in adult male and female rats for at least 7 weeks after administration (Tannenbaum et al, 1992), interfered with thyroid hormone activity (DiPippo and Powers, 1997;Fitts et al, 1998), and enhanced modulation by exogenous androgen of selected P450 enzymes in adult female rats (Chang et al, 1996). Chronic tamoxifen treatment affects endocrine-mediated responses such as somatic growth, uterine weight, and reproductive success that are dependent on gonadal, pituitary, and thyroid hormones (Bowman et al, 1983;MacGregor and Jordan, 1998). In rats, the sexually dimorphic pattern of GH secretion (Edén, 1979) plays a major regulatory role in the hepatic expression of P450 enzymes such as CYP2A1, CYP2C11, and CYP2C12 (Waxman and Chang, 1995).…”

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confidence: 99%

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Persistent Suppression of Hepatic CYP2A1 Expression and Serum Triiodothyronine Levels by Tamoxifen in Intact Female Rats: Dose-Response Analysis and Comparison with 4-Hydroxytamoxifen, Fulvestrant (ICI 182,780), and 17β-Estradiol-3-benzoate

Ickenstein

Bandiera²

2002

J Pharmacol Exp Ther

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Tamoxifen, a nonsteroidal antiestrogen, is used widely in the treatment of breast cancer and is undergoing evaluation as a chemopreventive agent. In this study, we investigated several long-term effects of tamoxifen in intact adult female rats following acute treatment at various dosages. The effects of tamoxifen on somatic growth, growth hormone (GH) levels, thyroid hormone levels, and on hepatic cytochrome P450 (P450) expression were compared with those of fulvestrant (ICI 182,780), 17␤-estradiol-3-benzoate, and 4-hydroxytamoxifen under the same experimental conditions. Each compound was injected s.c. for two consecutive days, and rats were killed 37 days after treatment. Tamoxifen decreased body weight and serum triiodothyronine (T3) levels at dosages ranging from 0.5 to 200 mg/kg. Ovary weight, uterus weight, peak plasma GH concentration, and hepatic CYP2A1 content were decreased 37 days after treatment with tamoxifen at a dosage of 20 mg/kg, but expression of other P450 enzymes was not affected. However, tamoxifen and 4-hydroxytamoxifen could not be detected in plasma by high performance liquid chromatography analysis at this time, which suggests that the effects of tamoxifen were mediated indirectly. 4-Hydroxytamoxifen exhibited effects similar to those of tamoxifen, indicating that this metabolite contributes to the in vivo activity of tamoxifen. Estradiol benzoate decreased CYP2A1 and increased CYP3A hepatic levels, but had no effect on serum T3 concentration. In contrast, treatment with ICI 182,780 had little or no effect on the endpoints measured. In summary, 2-day tamoxifen treatment of intact adult female rats resulted in persistent suppression of somatic growth, serum T3 levels, and hepatic CYP2A1 expression.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 53%

mentioning

confidence: 99%

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Persistent Suppression of Hepatic CYP2A1 Expression and Serum Triiodothyronine Levels by Tamoxifen in Intact Female Rats: Dose-Response Analysis and Comparison with 4-Hydroxytamoxifen, Fulvestrant (ICI 182,780), and 17β-Estradiol-3-benzoate

Ickenstein

Bandiera²

2002

J Pharmacol Exp Ther

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“…Estrogen has at least two types of nuclear receptors (␣ and ␤ receptors) (40), and TAM has binding affinity for both types of receptors to varying degrees (45). In vivo, TAM antagonizes estrogen-induced changes in uterine luminal fluid, prolactin, luteinizing hormone secretion, and lordosis behavior (46). Based on its antiestrogenic properties, TAM has been used as a tool to evaluate the role of estrogen in sexually dimorphic behaviors such as anxiety (47), agonistic behavior (e.g., ref.…”

Section: Discussionmentioning

confidence: 99%

Stress facilitates classical conditioning in males, but impairs classical conditioning in females through activational effects of ovarian hormones

Wood

Shors

1998

Proc. Natl. Acad. Sci. U.S.A.

331

249

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Exposure to restraint and brief intermittent tailshocks facilitates associative learning of the classical conditioned eyeblink response in male rats. Based on evidence of sex differences in learning and responses to stressful events, we investigated sexually dimorphic effects of a stressor of restraint and intermittent tailshock on classical eyeblink conditioning 24 h after stressor cessation. Our results indicate that exposure to the acute stressor had diametrically opposed effects on the rate of acquisition of the conditioned response in male vs. female rats. Exposure to the stressor facilitated acquisition of the conditioned response in males, whereas exposure to the same stressful event dramatically impaired acquisition in females. We further demonstrate that the stress-induced impairment in female conditioning is dependent on the presence of ovarian hormones. Conditioning of stressed sham-ovariectomized females was significantly impaired relative to the unstressed controls, whereas conditioning in stressed ovariectomized females was not impaired. We present additional evidence that estrogen mediates the stressinduced impairment in female acquisition. Females administered sesame oil vehicle and then stressed were significantly impaired relative to their unstressed controls, whereas females administered the estrogen antagonist tamoxifen prior to stress were not impaired. In summary, these results indicate that exposure to the same aversive event can induce opposite behavioral responses in males vs. females. These effects underscore sex differences in associative learning and emotional responding, and implicate estrogen in the underlying neuronal mechanism.

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“…Most of the additional effects of tamoxifen on lipid metabolism, changes of body weight and composition, or endometrium have been assumed to be due to estrogenic effects [5][6][7][8][9][10][11][12]. Since rats that are treated with tamoxifen have a decreased food intake and body weight gain [14,15] and reduced fat components [16], we have focused our interest on the influence of adipose tissue.…”

Section: Introductionmentioning

confidence: 99%

Plasma Leptin Concentration in Tamoxifen-Treated Ovariectomized Rats

Hozumi¹,

Hakamata

Nagai³

2005

Gynecol Obstet Invest

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Leptin, the ob gene product, has an important role in the regulation of body weight. Although tamoxifen, a nonsteroidal antiestrogenic agent, is known to have estrogenic effects on fat metabolism, its influence on adipose tissue remains unknown. In the present study, the effect of tamoxifen on the concentration of leptin was investigated in ovariectomized rats treated with tamoxifen or vehicle. The dosage of tamoxifen was extrapolated from the human dosage. Food intake, adipose tissue weight, and plasma insulin were assessed at the end of the experiment. Results: Tamoxifen-treated rats showed a significant reduction of body weight gain, food intake, adipose tissue weight and leptin concentration (p < 0.001). The plasma insulin level was significantly higher after tamoxifen treatment (p = 0.01) in tamoxifen-treated rats than in control rats. We concluded that tamoxifen reduces food intake in the acute phase and a reduction of adipose tissue gain may result in reduced levels of plasma leptin in ovariectomized rats. Furthermore, rats treated with tamoxifen may be resistant to insulin action.

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The biological activity of a single dose of tamoxifen in the adult ovariectomized rat

Cited by 10 publications

References 20 publications

Persistent Suppression of Hepatic CYP2A1 Expression and Serum Triiodothyronine Levels by Tamoxifen in Intact Female Rats: Dose-Response Analysis and Comparison with 4-Hydroxytamoxifen, Fulvestrant (ICI 182,780), and 17β-Estradiol-3-benzoate

Persistent Suppression of Hepatic CYP2A1 Expression and Serum Triiodothyronine Levels by Tamoxifen in Intact Female Rats: Dose-Response Analysis and Comparison with 4-Hydroxytamoxifen, Fulvestrant (ICI 182,780), and 17β-Estradiol-3-benzoate

Stress facilitates classical conditioning in males, but impairs classical conditioning in females through activational effects of ovarian hormones

Plasma Leptin Concentration in Tamoxifen-Treated Ovariectomized Rats

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