Age-correlated and ovary-dependent changes in relationships between plasma estradiol and luteinizing hormone, prolactin, and growth hormone in female C57BL/6J mice

Abstract

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.