Chemopreventive Effects of Hydroxymatairesinol on Uterine Carcinogenesis in Donryu Rats

Katsuda, Shin-ichi; Yoshida, Midori; Saarinen, Niina M.; Smeds, Annika; Nakae, Dai; Santti, Risto; Maekawa, Akihiko

doi:10.1177/153537020422900510

Cited by 22 publications

(20 citation statements)

References 37 publications

(50 reference statements)

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“…These features indicated that ovarian hormonal imbalance is crucial for uterine carcinogenesis in rats as well as humans [2][3][4]. Many previous studies have provided evidence that delayed onset of PE and/or depression of the serum E2 level can prevent adenocarcinoma development in rats [31][32][33]. The present study supports our hypothesis that an increased E:P ratio is very important for promoting effects on uterine carcinogenesis.…”

supporting

confidence: 81%

Long-Term Treatment with Bromocriptine Inhibits Endometrial Adenocarcinoma Development in Rats

Yoshida

Watanabe

Suzuki

et al. 2009

Journal of Reproduction and Development

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Abstract. The effects of long-term blockade of prolactin (PRL) action by bromocriptine (BRC) treatment on uterine carcinogenesis and on related ovarian physiology were investigated using a rat uterine cancer model. Ten-week-old cycling female Donryu rats, a high yield strain for uterine corpus tumors (endometrial adenocarcinomas), were treated with N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG), as a tumor initiator, and injected with 1 mg/kg body weight BRC subcutaneously 4 times per week until 14.5 months of age to block the proestrus PRL surge. The study was terminated at 15 months of age, and the results showed that long-term BRC treatment significantly inhibited endometrial adenocarcinoma development in terms of both incidence (34.6% to 13.0% with significant difference at 5%) and multiplicity (0.35 to 0.18 with significant difference at 5%), which indicates the number of adenocarcinomas per animals. While BRC did not affect estrous cyclicity in the treated animals, a significant decline was evident in the serum 17β-estradiol (E2) to progesterone (P) ratio (E: P ratio), and the serum E2 level showed a decreased tendency at 15 months of age. While the precise pathway to the inhibitory effect could not be determined; the pathway by which ovarian hormonal imbalance decreases the serum E: P ratio most likely plays a crucial role. Key words: Bromocripchne, Long-term treatment, Prolactin blockade, Rat, Uteirne carcinogenesis (J. Reprod. Dev. 55: [105][106][107][108][109] 2009) varian steroidhormone imbalance contributes to uterine carcinogenesis in human beings [1]. Maekawa et al. [2][3][4] have provided evidence that a similar imbalance, especially elevated 17β-estradiol (E2) levels relative to progesterone (P) levels (the E:P ratio), plays a crucial role in promoting endometrial adenocarcinoma development in rodents. While it is well-established that E2 and estrogenic chemicals play supportive or sometimes initiative roles in uterine carcinogenesis in rats as well as women, P may exert an inhibitory influence on human uterine cancer development [5][6][7]. However, the effects of other hormones related to the pituitary or ovaries on uterine carcinogenesis are not well known.Prolactin (PRL) is one of the important regulators of the corpus luteum as well as luteinizing hormone (LH), prostaglandin and vascular endothelial growth factors and platelet derived growth factors in rats [8][9][10]. The function of PRL as a luteotrophic and luteolytic hormone, however, is very complex [11][12][13][14][15][16][17]. Repeated injection of PRL has been shown to stimulate rapid regression of the persistent corpus luteum, with a concomitant decline in total steroidogenic capacity [12,18]. These studies indicate the possibility that the modulation of P production induced by PRL or its inhibitor affect uterine carcinogenesis through ovarian hormonal imbalance. On the other hand, PRL receptors, especially long-form ones (PRLR-L) [19], are present in the uteri of rats. PRL is known to play important roles in adenomyosis formation in ...

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confidence: 81%

Long-Term Treatment with Bromocriptine Inhibits Endometrial Adenocarcinoma Development in Rats

Yoshida

Watanabe

Suzuki

et al. 2009

Journal of Reproduction and Development

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“…In this rat model, imbalance in ovarian hormones leads to elevation of the serum E2/progesterone ratio, and it was recognized that ovarian atrophy plays an essential role for the endometrial adenocarcinoma development, similar to the case in humans [1,2,11]. Using this model, many studies have proven that early and delayed occurrence of PE induced by chemicals promotes and prevents the endometrial adenocarcinoma development, respectively [22,23]. Therefore, the earlier occurrence of PE in the present study is considered to be crucial for the promoting effect on uterine cancer.…”

Section: Discussionmentioning

confidence: 99%

Reduction of Primordial Follicles Caused by Maternal Treatment with Busulfan Promotes Endometrial Adenocarcinoma Development in Donryu Rats

Yoshida

Watanabe

Shirota

et al. 2005

Journal of Reproduction and Development

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Abstract.Ovarian dysfunction leading to hormonal imbalance plays a crucial role in uterine carcinogenesis in rats as well as women. However, the effects of a reduction in primordial follicles at birth on uterine adenocarcinoma development have hitherto not been determined. The present study was therefore conducted using female Donryu rats, a high incidence rat strain of uterine adenocarcinoma. The animals were maternally exposed to 2.5 or 5.0 mg/kg of busulfan on gestation day 14 to reduce primordial follicles, and were then initiated by intrauterine treatment with N-ethyl-N'-nitro-N-nitrosoguanidine at 11 weeks of age. Both busulfan treatment doses caused earlier occurrence of persistent estrus, with dose-dependence as compared to controls. At 15 months of age, the rats were euthanized. The incidence of uterine adenocarcinomas and multiplicity of uterine neoplastic lesions were significantly increased by the 5.0 mg/kg, but not the 2.5 mg/kg busulfan treatment. Morphologically, the ovaries exposed to busulfan treatment exhibited severe atrophy, with few or no follicles and corpus lutea. Serum 17β-estradiol (E2), progesterone, and inhibin levels were significantly decreased in the busulfan treatment groups, with a clear dose-relation. Interestingly, only the 5.0 mg/kg busulfan treatment elevated the E2/progesterone ratio. These results provide evidence that the reduction of primordial follicles promotes uterine adenocarcinoma development in rats in association with an earlier occurrence of the persistent estrus status.

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“…The pharmacological profile of HMR includes chemopreventive effects [7,[11][12][13], antioxidant properties [7,9], and mild proestrogenic activity [7,14,15]. In particular, HMR seems to be provided with strong antioxidative capacity independent from its estrogenic profile [7,8,15].…”

Section: Introductionmentioning

confidence: 98%

Immunomodulatory activity of the lignan 7-hydroxymatairesinol potassium acetate (HMR/lignan™) extracted from the heartwood of Norway spruce (Picea abies)

Cosentino

Marino

Maio

et al. 2010

International Immunopharmacology

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Chemopreventive Effects of Hydroxymatairesinol on Uterine Carcinogenesis in Donryu Rats

Cited by 22 publications

References 37 publications

Long-Term Treatment with Bromocriptine Inhibits Endometrial Adenocarcinoma Development in Rats

Long-Term Treatment with Bromocriptine Inhibits Endometrial Adenocarcinoma Development in Rats

Reduction of Primordial Follicles Caused by Maternal Treatment with Busulfan Promotes Endometrial Adenocarcinoma Development in Donryu Rats

Immunomodulatory activity of the lignan 7-hydroxymatairesinol potassium acetate (HMR/lignan™) extracted from the heartwood of Norway spruce (Picea abies)

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