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Effects of Energy Restriction on Mouse Mammary Tumor Virus mRNA Levels in Mammary Glands and Uterus and on Uterine Endometrial Hyperplasia and Pituitary Histology in C3H/SHN F1 Mice^{1, 2,}

Department of Hygiene, Akita University School of Medicine, Akita 010, Japan ^* National Institute on Aging, National Institutes of Health, Bethesda, MD 20892

We investigated the effects of energy restriction on the pituitary-ovarian axis and on a hormone responsive gene, the mouse mammary tumor virus (MMTV). Female C3H/SHN F1-hybrid mice, known to display a high incidence of mammary tumors, ate an energy-restricted diet (48 kcal/wk) or a control diet (95 kcal/wk) beginning at the time of weaning. By 67 wk of age, 12 of 32 mice in the control group, but none of the 33 mice in the energy-restricted group, had developed mammary tumors. Six tumor-free mice from each group were studied in detail at 67 wk of age. All six tumor-free control mice, but none of the six energy-restricted mice, showed uterine endometrial hyperplasia at autopsy. Mice subjected to energy restriction did not display an estrous cycle. The average levels of MMTV mRNA in mammary glands and uteri were strongly reduced by energy restriction. MMTV mRNA levels in mammary glands from control mice were two orders of magnitude lower than those in mammary tumors. Energy restriction lowered the percentage of pituitary mammatropes and suppressed proliferation of mammatropes with advancing age. Energy restriction thus appeared to inhibit endometrial hyperplasia and to decrease MMTV production at the mRNA level in the mammary glands and in the uterus. These effects may be a consequence of hormonal changes originating at the pituitary-ovarian axis.

KEY WORDS: • energy restriction • MMTV mRNA • mammatropes • mice

¹ A part of this work was presented at the 59th Annual Meeting of Japanese Society for Hygiene, held in Akita May 2–4, 1989, and at the 60th Annual Meeting of Japanese Society for Hygiene, held in Fukuoka March 31–April 2, 1990.

² This study was supported by a grant-in-aid for 1989 (No. 63577024 and No. 01870027) from the Ministry of Education, Science and Culture of the government of Japan.

Manuscript received 9 January 1990. Revision accepted 1 June 1990.