Levels of A-Inhibin in Aging Female Mice1

α-inhibin was immunocytochemically localized in granulosa cells of different stages of developing follicles, freshly formed corpora lutea, and scattered interstitial cells (pigmented or ceroid cells) in ovaries of 6-, 14-, and 23–25-mo-old C57BL/6NNia mice. Developing follicles exhibited the greatest amount of staining. Quantitation of the stain using an image analysis system indicated the staining intensity within ovarian follicles of 14-mo-old mice was greater than that in 23–25-mo-old mice. The levels of plasma α-inhibin and estradiol (E2) decreased with age. The number of follicles present in ovaries of middle-aged mice was comparable to those of 6-mo-old mice, yet plasma levels of FSH were significantly higher than those of 6-mo-old mice. This may be due to an age-related loss in the sensitivity of the hypothalamus and/or pituitary of middle-aged mice to ovarian hormones. In contrast, ovaries of 23–25-mo-old mice contained few antral follicles and consequently produced little α-inhibin. There appeared to be little negative feedback regulation of FSH secretion in 23–25-mo-old mice as a result of age-related ovarian impairments. This study supports an earlier hypothesis from our laboratory [Biol Reprod 1985; 32:989–997] that the primary defect(s) limiting age-related reproductive performance in mice appears to reside within the hypothalamo-hypophyseal axis, whereas secondary defects arise from the ovary.