Aging and the regulation of luteinizing hormone in C57BL/6J mice: impaired elevations after ovariectomy and spontaneous elevations at advanced ages

Abstract

The effects of age on the elevations of plasma luteinizing hormone (LH) after ovariectomy were studied in C57BL/6J mice. In longitudinal studies, mice ovariectomized at 4-6 months and sampled serially reached maximum plasma LH (200-300 ng/ml) after 1 month; these elevations were maintained to at least 15 months of age, when most intact mice have ceased cycling and have persistent vaginal cornification (PVC). In contrast, mice ovariectomized at 15 or 21 months had smaller LH elevations (to 150 ng/ml) 1 or 2 months after ovariectomy, as compared to younger (5- or 11-month-old) cycling mice whose LH was ca. 200 ng/ml 1 month after ovariectomy. The maintenance of LH elevations in chronically ovariectomized mice suggests that the smaller LH elevations in acutely ovariectomized mice of the same age may be an ovary-dependent aging phenomenon. Pilot studies detected no age effects on plasma LH turnover. Intact 20- to 26-month-old mice with leukocytic vaginal smears, low plasma estradiol (E2) and low progesterone had initially elevated plasma LH (ca. 125 ng/ml), if gross pathologic lesions were not present at necropsy. In contrast, old mice with cornified vaginal smears had higher plasma E2 and low (normal) plasma LH. The low plasma progesterone and elevated LH in older mice with leukocytic smears argues against a pseudopregnant status. Old mice of all vaginal smear types with pathologic lesions had low LH. Ovariectomy did not yield further increases of LH in old mice. The spontaneous elevation of plasma LH to ovariectomized levels in old intact mice with leukocytic vaginal smears and reduced plasma E2 implies that C57BL/6J mice eventually undergo ovarian changes analogous to menopause in humans.