Effects of different durations of estrogen and progesterone treatment on development of N-methyl-N-nitrosourea-induced mammary carcinomas in female Lewis rats

Takashi Yuri, Reiko Tsukamoto, Norihisa Uehara, Yoichiro Matsuoka, Airo Tsubura

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: There have been no precise evaluations of the effects of different durations of exposure to estrogen and progesterone pregnancy levels on mammary carcinogenesis risk. We examined such effects on the development of N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinoma. Materials and Methods: Female Lewis rats were administered a single intraperitoneal injection of 50 mg/kg MNU at 28 days of age, and then were either left hormone-untreated (control group), or underwent subcutaneous implantation of a 21-day release pellet containing 0.5 mg 17β- estradiol and 32.5 mg progesterone (E/P pellet) at 42 days of age. The pellet was either replaced every 3 to 4 weeks throughout the experimental period (long-term E/P group), or was implanted only once (short-term E/P group). Circulating 17β-estradiol and progesterone levels in the serum, and expression of estrogen receptor (ER) a and progesterone receptor (PgR) in the normal mammary gland were measured. The rats were sacrificed when they developed a mammary tumor with a diameter of ≥1 cm, or when they reached the age of 29 weeks. Results: In rats implanted with a single E/P pellet, circulating 17β-estradiol and progesterone levels were significantly elevated 2 weeks after implantation, but returned to control levels 8 weeks after implantation; 17β-estradiol transiently reached pregnancy levels. In normal mammary glands of rats sacrificed at 29 weeks of age, both long- and short-term E/P treatment decreased the percentage of ERα- and PgR-positive cells. Rats that received long- or short-term E/P treatment had a decreased incidence of mammary carcinoma with a diameter of ≥1 cm, compared to control rats. However, when histologically detected microcarcinomas (diameter <1 cm) were included for comparison, the E/P- treated groups exhibited an abrupt increase in the number of microcarcinomas from 22 to 25 weeks after MNU injection. Although short-term E/P treatment significantly suppressed mammary carcinomas of all sizes, long-term E/P treatment had no cancer-suppressing effect. Conclusion: The duration of E/P treatment is an essential factor for the suppression of mammary carcinogenesis.

Original languageEnglish
Pages (from-to)829-836
Number of pages8
JournalIn Vivo
Volume20
Issue number6 B
Publication statusPublished - Nov 1 2006
Externally publishedYes

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Methylnitrosourea
Progesterone
Rats
Estrogens
Breast Neoplasms
Estradiol
Progesterone Receptors
Estrogen Receptors
Human Mammary Glands
Therapeutics
Rat control
Carcinogenesis
Breast
Level control
Pregnancy
Intraperitoneal Injections
Tumors
Cells
Hormones
Control Groups

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology

Cite this

Effects of different durations of estrogen and progesterone treatment on development of N-methyl-N-nitrosourea-induced mammary carcinomas in female Lewis rats. / Yuri, Takashi; Tsukamoto, Reiko; Uehara, Norihisa; Matsuoka, Yoichiro; Tsubura, Airo.

In: In Vivo, Vol. 20, No. 6 B, 01.11.2006, p. 829-836.

Research output: Contribution to journalArticle

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abstract = "Background: There have been no precise evaluations of the effects of different durations of exposure to estrogen and progesterone pregnancy levels on mammary carcinogenesis risk. We examined such effects on the development of N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinoma. Materials and Methods: Female Lewis rats were administered a single intraperitoneal injection of 50 mg/kg MNU at 28 days of age, and then were either left hormone-untreated (control group), or underwent subcutaneous implantation of a 21-day release pellet containing 0.5 mg 17β- estradiol and 32.5 mg progesterone (E/P pellet) at 42 days of age. The pellet was either replaced every 3 to 4 weeks throughout the experimental period (long-term E/P group), or was implanted only once (short-term E/P group). Circulating 17β-estradiol and progesterone levels in the serum, and expression of estrogen receptor (ER) a and progesterone receptor (PgR) in the normal mammary gland were measured. The rats were sacrificed when they developed a mammary tumor with a diameter of ≥1 cm, or when they reached the age of 29 weeks. Results: In rats implanted with a single E/P pellet, circulating 17β-estradiol and progesterone levels were significantly elevated 2 weeks after implantation, but returned to control levels 8 weeks after implantation; 17β-estradiol transiently reached pregnancy levels. In normal mammary glands of rats sacrificed at 29 weeks of age, both long- and short-term E/P treatment decreased the percentage of ERα- and PgR-positive cells. Rats that received long- or short-term E/P treatment had a decreased incidence of mammary carcinoma with a diameter of ≥1 cm, compared to control rats. However, when histologically detected microcarcinomas (diameter <1 cm) were included for comparison, the E/P- treated groups exhibited an abrupt increase in the number of microcarcinomas from 22 to 25 weeks after MNU injection. Although short-term E/P treatment significantly suppressed mammary carcinomas of all sizes, long-term E/P treatment had no cancer-suppressing effect. Conclusion: The duration of E/P treatment is an essential factor for the suppression of mammary carcinogenesis.",
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T1 - Effects of different durations of estrogen and progesterone treatment on development of N-methyl-N-nitrosourea-induced mammary carcinomas in female Lewis rats

AU - Yuri, Takashi

AU - Tsukamoto, Reiko

AU - Uehara, Norihisa

AU - Matsuoka, Yoichiro

AU - Tsubura, Airo

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