Koizumi A, Masuda H, Wada Y, Tsukada M, Kawamura K, Kamiyama S, Walford R L
Department of Hygiene, Akita University School of Medicine, Japan.
Mech Ageing Dev. 1989 Aug;49(2):93-104. doi: 10.1016/0047-6374(89)90093-6.
Dietary restriction (DR) retards aging and extends maximum life span. It is also known to decrease the incidence of hormone-dependent tumors. In the present investigation, we focussed primarily on the influence of DR on the pituitary-ovarian axis, and subsequently on gene expression of the mouse mammary tumor virus. F1 females from the mating of SHN female and C3H male mice were used in this study, since these hybrids display a very high incidence of mouse mammary tumors. The mice weaned at 3 weeks were raised on either a calorically-restricted diet (DR: 50 kcal/week; N = 5) or on a control diet (C: 95 kcal/week N = 5) for 5 weeks. Three C57BL/6J Jcl ad libitum-fed female mice, 8 weeks of age, were used as reference animals since this strain has a very low incidence of mammary tumors. The mean cellular contents of prolactin (PRL) and growth hormone (GH) in the pituitary, as determined by immunohistochemistry, were found to be reduced in mice raised on the DR diet. The decrease in the mean cellular content of PRL (50% of the mean control value) was accompanied by a decrease in the number of lactotrophs (17% of the mean value of control diet mice). However, the decrease in cellular content of GH (53% of the mean control value) was not accompanied by a decrease in the number of somatotrophs (no. of somatotrophs in DR = 103% of mean control value). Histologically, ovaries from DR mice showed many growing and atretic follicles, with few corpora lutea. In contrast, both control-diet and reference (C57BL/6J Jcl) mice showed two or three corpora lutea per ovarian section. In accordance with this finding, DR mice had not established stable estrus cycles by 8 weeks of age, in contrast to both control-diet and reference mice. Since caloric restriction has been shown to decrease mammary tumor virus (MMTV) gene expression, MMTV production was investigated by electron microscopy to confirm the validity of our experimental conditions. In DR or reference C57BL/6J Jcl mice, MMTV particles were rarely found in the mammary gland samples, but were always found in samples from control mice. The development of mammary glands, as indicated by the number of villi or the development of the rough endoplasmic reticulum, was delayed in DR mice. Thus, it was concluded that caloric restriction decreases the number of lactrotrophs, inhibits ovulation and delays mammary gland development. This immature status is considered to be due to perturbations in the pituitary-ovarian axis by caloric restriction.
饮食限制（DR）可延缓衰老并延长最大寿命。众所周知，它还能降低激素依赖性肿瘤的发病率。在本研究中，我们主要关注饮食限制对垂体 - 卵巢轴的影响，以及随后对小鼠乳腺肿瘤病毒基因表达的影响。本研究使用了SHN雌性小鼠与C3H雄性小鼠交配产生的F1雌性小鼠，因为这些杂交后代显示出非常高的小鼠乳腺肿瘤发病率。3周龄断奶的小鼠分别采用热量限制饮食（DR：50千卡/周；N = 5）或对照饮食（C：95千卡/周；N = 5）饲养5周。选用3只8周龄自由采食的C57BL/6J Jcl雌性小鼠作为参照动物，因为该品系的乳腺肿瘤发病率非常低。通过免疫组织化学测定发现，采用DR饮食饲养的小鼠垂体中催乳素（PRL）和生长激素（GH）的平均细胞含量降低。PRL平均细胞含量的降低（为对照平均值的50%）伴随着催乳细胞数量的减少（为对照饮食小鼠平均值的17%）。然而，GH细胞含量的降低（为对照平均值的53%）并未伴随着促生长激素细胞数量的减少（DR组促生长激素细胞数量为对照平均值的103%）。组织学检查显示，DR小鼠的卵巢中有许多生长中的卵泡和闭锁卵泡，黄体很少。相比之下，对照饮食小鼠和参照（C57BL/6J Jcl）小鼠的每个卵巢切片中都有两三个黄体。根据这一发现，与对照饮食小鼠和参照小鼠相比，DR小鼠在8周龄时尚未建立稳定的发情周期。由于热量限制已被证明可降低乳腺肿瘤病毒（MMTV）基因表达，因此通过电子显微镜研究MMTV的产生以确认我们实验条件的有效性。在DR组或参照C57BL/6J Jcl小鼠的乳腺样本中很少发现MMTV颗粒，但在对照小鼠的样本中总能发现。DR小鼠乳腺绒毛数量或粗面内质网的发育所显示的乳腺发育延迟。因此，得出的结论是热量限制会减少催乳细胞数量，抑制排卵并延迟乳腺发育。这种未成熟状态被认为是由于热量限制对垂体 - 卵巢轴的干扰所致。
