Exposure to estradiol impairs luteinizing hormone function during aging

The loss of ovulatory cyclicity in many mammals is caused by changes in the hypothalamic-pituitary (H-P) control of the preovulatory luteinizing hormone (LH) surge. This work evaluated the anterior pituitary (AP) component of the H-P axis by determining the ability of perifused AP to release LH following sustained but pulsatile LHRH stimulation. The normal dual discharge profile of LH was affected by age. The first hour of the response, unaffected by cycloheximide, was similar in 5-6-month-old (mature), 12-13-month-old (declining litters) and 16-18-month-old (irregularly cycling) mice. The remaining protein synthesis-dependent part of the response was reduced in the 16-18 and 22-24-month-old (anestrus) mice. The role of estradiol (E2) in AP aging was further tested as AP from ovariectomized (OVXed) mice, deprived of E2 since puberty, responded as well as the mature proestrous group. In contrast, aged mice subjected to long-term E2 exposure (cycling or OVXed plus E2 replacement) failed to produce the dual response pattern. Since alterations in LH response occurred during the protein-dependent phase, synthetic processes that involve packaging and transport of stored LH, or the production of new LH, may be affected by age. Furthermore, E2 is a major factor in altering LH function and appears to act before middle age.