Chronological Changes in Sex Steroid, Gonadotropin and Prolactin Secretion in Aging Female Rats Displaying Different Reproductive States1

Abstract

Longitudinal studies were performed in a colony of aging female rats, from 4–33 months of age, to determine the chronological change in reproductive patterns and the changes in sex steroid, prolactin and gonadotropin secretion associated with different reproductive states. The present study demonstrates that the incidence (65%) of irregular estrous cycles in aging rats increased abruptly from 10–12 months of age. Subsequently, female rats became chronically anovulatory with persistent vaginal cornifications and their ovaries contained developed follicles but no corpora lutea. The highest incidence (65%) of constant estrous (CE) rats occurred at the age of about 19 months. During the anovulatory state, CE rats displayed low to medium levels of serum estradiol, estrone, testosterone and androstenedione, low levels of progesterone and minimal levels of 20α-hydroxyprogesterone. Preovulatory increases in gonadotropin and prolactin release, similar to those seen in young cycling rats on proestrus, were not observed in CE rats. Whereas serum basal LH levels remained unaltered, morning FSH levels were increased in CE rats. The latter may account for the persistent follicular development in aging rats during chronic anovulatory state. Serum basal prolactin levels were normal in CE rats during the early phase (11–16 months of age) of the anovulatory state, but were subsequently increased 3 to 4-fold beyond 24 months of age. Moreover, ovariectomy at a young age prevented the increased pituitary prolactin release in old female rats. These results suggest that continuous exposure to medium levels of estrogens, particularly in the presence of sustained low progesterone secretion, may alter pituitary secretion of prolactin in aging rats. With further advance of age and following many months of anovulatory function, aging female rats exhibited ovulatory activity at irregular intervals. After each ovulation, formed corpora lutea were maintained for a prolonged period, presumably due in part to the existing high prolactin levels in the circulation of older female rats. These corpora lutea in old “pseudopregnant (PSP)” rats were functional as indicated by active secretion of progestins, with 20α-hydroxyprogesterone levels greater than those of progesterone in the circulation. These results indicate that the ovaries of aging rats retain their functional capacity to develop follicles and corpora lutea and to secrete steroid hormones. Although the cause(s) responsible for cessation of normal ovulatory cycles in aging female rats is unknown, the present study demonstrates that the chronic anovulatory state in aging female rats is characterized by significantly reduced ovarian secretion and the lack of cyclic increases in pituitary gonadotropin and prolactin release. The causal relationships between the decreased ovarian steroid production and the absence of preovulatory surges of gonadotropin release in aging CE rats remain to be determined.