An assessment of agonist/antagonist effects of tamoxifen in the female mouse brain*1

McKenna, Suzanne; Simon, Neal G.; Cologer-Clifford, Athena

doi:10.1016/0018-506x(92)90020-v

Cited by 32 publications

(12 citation statements)

References 23 publications

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“…These results suggest that treatment with PM-100 affects the estrous cycle and mating behavior of female mice and subsequently results in reduced pregnancy rates and litter sizes. Previous studies have shown that treatment with soy supplement and tamoxifen (antiestrogen) suppresses lordosis in estrogen-and progesterone-primed female rats [32][33][34][35]. As mentioned above, treatment with PM-100 reduced the serum FSH and LH levels of the mice, and we suspected that there was a subsequent reduction in the estrogen level, although we did not determine the level of this hormone in the current study.…”

Section: Discussioncontrasting

confidence: 45%

Assessment of Fertility and Reproductive Toxicity in Adult Female Mice after Long-Term Exposure to Pueraria mirifica Herb

Jaroenporn

Malaivijitnond

Wattanasirmkit

et al. 2007

Journal of Reproduction and Development

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Abstract. The present study investigated the effects of long-term administration of Pueraria mirifica (PM) at non-toxic doses on the ovarian function and fertility of adult female mice based on evaluation of hematological and biochemical parameters [1]. Female mice were divided into 4 groups (36 mice/ group). Groups 1-3 were orally treated with a dose of 0 (PM-0), 10 (PM-10) or 100 mg/kg BW/day PM (PM-100), and group 4 was subcutaneously injected with 200 µg/kg BW/day of synthetic estrogen diethylstilbestrol (DES). The treatment schedule was separated into treatment and post-treatment periods. The duration of each period was 8 weeks. The PM-10 mice exhibited regular estrous cycles, while the PM-100 and DES treatments induced prolonged estrous cycles. Although no changes were observed in the uterus and ovary weights of the mice after the PM-100 and DES treatments, hyperplasia of the uterine endothelium and a decrease in the number of growing ovarian follicles were detected. The changes in the ovarian histologies of the PM-100 and DES mice were related to reductions in the levels of LH and FSH, which subsequently caused a decrease in mating efficiency. Once the PM mice were able to copulate, they were capable of successfully becoming pregnant and mothering offspring. No abnormalities were observed in the external morphologies and reproductive organ weights of the 50-day-old offspring. In conclusion, our results suggest that long-term exposure to 100 mg/kg BW of PM has adverse effects on the mating efficiency and reproduction of adult female mice and that administration of 10 mg/kg BW of PM does not induce any changes in the hypothalamic-pituitary-ovarian-uterine axis.

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Section: Discussioncontrasting

confidence: 45%

Assessment of Fertility and Reproductive Toxicity in Adult Female Mice after Long-Term Exposure to Pueraria mirifica Herb

Jaroenporn

Malaivijitnond

Wattanasirmkit

et al. 2007

Journal of Reproduction and Development

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“…The estrogenic effects of tamoxifen that have been noted in other tissues have been attributed to effects on estrogen receptor f unction that involve actions other than those mediated by estrogen receptor-ERE interactions (Webb et al, 1995) possibly via AP-1 sites. Tamoxifen has been shown to block the actions of estrogen in brain, both on estrogen-induced sexual behavior and induction of progesterone receptor mRNA (McKenna et al, 1992). ICI 182,780 interferes with activated hormone-receptor complex binding to DNA by preventing dimerization and nuclear translocation.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Effects of Estrogen on Neuronal Neurotensin Gene Expression Involve cAMP/Protein Kinase A-Dependent Signaling Mechanisms

Watters¹,

Dorsa

1998

J. Neurosci.

160

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Steroid hormones exert dramatic effects on neuronal expression of genes that encode neuropeptides. Expression of the neurotensin/neuromedin (NT/N) gene in preoptic area neurons is dramatically enhanced by estrogen in vivo, even though its promoter lacks palindromic estrogen response elements. We report here that estrogen promotes transcription of this gene by interactions with the cAMP cascade in a neuronal cell line, SK-N-SH, and in a mouse model. In neuroblastoma cells, estrogen increases cAMP and the phosphorylation of the cAMP response element-binding protein in a time frame that precedes induction of NT/N gene transcription. Interference with the cAMP/protein kinase A signal transduction cascade blocks the ability of estrogen to elicit increases in transcription of this gene. Furthermore, in studies performed in vivo using mice deficient in protein kinase A, estrogen fails to induce increases in NT/N mRNA but retains its ability to promote estrogen response element-dependent progesterone receptor gene transcription. These data represent the first report of a nonclassical effect of estrogen on the expression of an endogenous estrogen-regulated neuropeptide gene through cAMPmediated mechanisms both in a neuroblastoma cell line and in hypothalamic neurons. More importantly, this "cross-talk" may represent a more generalized mechanism by which steroid hormones act through other signal transduction cascades to regulate the expression of other genes in the brain.

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“…Moreover, in the United States, it is estimated that based on year 2000 census data more than 2 million women could benefit from prophylactic use of TAM (Freedman et al, 2003), highlighting the importance of understanding the potential neurocognitive side effects of this agent. TAM is known to have both agonist and antagonist effects in the periphery and in the brain (McKenna et al, 1992). It has also been reported to influence the production of proinflammatory cytokines (IL-1, IL-6, and TNF) that are associated with cognitive dysfunction (Järvinen et al, 1996).…”

Section: Hormonal Therapymentioning

confidence: 99%

Neuropsychological dysfunction associated with cancer and cancer therapies: a conceptual review of an emerging target

2004

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An assessment of agonist/antagonist effects of tamoxifen in the female mouse brain*1

Cited by 32 publications

References 23 publications

Assessment of Fertility and Reproductive Toxicity in Adult Female Mice after Long-Term Exposure to Pueraria mirifica Herb

Assessment of Fertility and Reproductive Toxicity in Adult Female Mice after Long-Term Exposure to Pueraria mirifica Herb

Transcriptional Effects of Estrogen on Neuronal Neurotensin Gene Expression Involve cAMP/Protein Kinase A-Dependent Signaling Mechanisms

Neuropsychological dysfunction associated with cancer and cancer therapies: a conceptual review of an emerging target

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