Mobbs C V, Cheyney D, Sinha Y N, Finch C E
Endocrinology. 1985 Feb;116(2):813-20. doi: 10.1210/endo-116-2-813.
Impairments in the estradiol (E2)-induced surge of LH occur as aging female rodents lose reproductive cycles. These and other impairments can be substantially attenuated by ovariectomy of the young adult. In female rats, plasma PRL tends to increase with age, whereas in male rats, GH tends to decrease; PRL is regulated by E2, whereas GH is probably not. To determine if age-correlated neuroendocrine impairments are accompanied by altered neuroendocrine sensitivity to E2, the relationships among plasma E2, LH, PRL, and GH were assessed in 6- and 12-month-old cycling and 18-month-old acyclic female C57BL/6J mice given E2 implants. An additional 18-month-old group, ovariectomized at 6 months of age, was examined to determine if age-correlated changes in sensitivity to E2 are ovary dependent. One week after ovariectomy, mice were given different sized E2 implants which generated a physiological range of plasma E2. Three weeks after implantation, plasma E2 correlated positively with implant size, uterine weight, and PRL, but correlated negatively with LH in each age group; age did not affect plasma E2 levels. The suppression of LH by E2 decreased progressively with age. Conversely, the elevation of PRL by E2 increased with age. These effects of age were largely prevented by ovariectomy at 6 months of age. Plasma GH decreased slightly with age, but was not significantly affected by E2; old mice ovariectomized when young had lower GH levels than previously intact old mice. GH also correlated positively with LH in all age groups. We conclude that neuroendocrine responses to E2 are altered with age even before estrous cycles are lost. Sensitivity to E2 may either increase or decrease, depending on the function. These effects of age can be attenuated by prolonged ovariectomy. Thus, chronic exposure to ovarian E2 during normal reproductive cycles may alter neuroendocrine sensitivity to E2, which may lead to age-correlated impairments in reproductive function.
随着雌性啮齿动物衰老并失去生殖周期，雌二醇（E2）诱导的促黄体生成素（LH）激增会出现障碍。这些以及其他障碍可通过对年轻成年动物进行卵巢切除术而得到显著缓解。在雌性大鼠中，血浆催乳素（PRL）往往会随着年龄增长而增加，而在雄性大鼠中，生长激素（GH）往往会减少；PRL受E2调节，而GH可能不受其调节。为了确定与年龄相关的神经内分泌障碍是否伴随着神经内分泌对E2的敏感性改变，对给予E2植入物的6月龄和12月龄有发情周期以及18月龄无发情周期的雌性C57BL/6J小鼠的血浆E2、LH、PRL和GH之间的关系进行了评估。另外还检查了一组在6月龄时进行卵巢切除的18月龄小鼠，以确定与年龄相关的对E2敏感性变化是否依赖于卵巢。卵巢切除术后一周，给小鼠植入不同大小的E2植入物，这些植入物产生了生理范围内的血浆E2。植入后三周，血浆E2与植入物大小、子宫重量和PRL呈正相关，但在每个年龄组中与LH呈负相关；年龄不影响血浆E2水平。E2对LH的抑制作用随着年龄增长而逐渐减弱。相反，E2对PRL的升高作用随着年龄增长而增强。6月龄时进行卵巢切除术在很大程度上预防了年龄的这些影响。血浆GH随着年龄略有下降，但不受E2显著影响；年轻时进行卵巢切除的老年小鼠的GH水平低于先前未切除卵巢的老年小鼠。在所有年龄组中，GH也与LH呈正相关。我们得出结论，即使在发情周期丧失之前，神经内分泌对E2的反应也会随着年龄而改变。对E2的敏感性可能会增加或降低，这取决于功能。年龄的这些影响可通过长期卵巢切除术得到缓解。因此，在正常生殖周期中慢性暴露于卵巢E2可能会改变神经内分泌对E2的敏感性，这可能导致与年龄相关的生殖功能障碍。
