Alterations in the Secretion and Production of Follicle-Stimulating Hormone Precede Age-Related Lengthening of Estrous Cycles in Rats*

The present study evaluated the effects of aging on the hormone profile of FSH as well as that of LH and PRL during proestrus (P) and estrus (E) of the 4-day rat estrous cycle. Furthermore, in view of the heterogeneity of FSH forms in the anterior pituitary gland (AP), we also sought to ascertain the effects of aging on the type of FSH produced by the AP. An attempt then was made to correlate possible changes in the synthesis and/or release of FSH with the initial decline in the incidence of regular 4-day estrous cycles in our colony of rats. Virgin rats aged 3, 5, 7, and 9 months, exhibiting 4-day estrous cycles were outfitted with atrial cannulae on proestrous morning. Blood samples were obtained every 4 h from 1400 h on P to 1000 h on E. At 1600 h on E, all rats were killed, trunk blood was collected, and the AP was removed, weighed, and homogenized. The concentrations of FSH, LH, and PRL in plasma and AP supernatant were determined by RIA, while the analysis of FSH isohormones in the remaining supernatant was made by chromatofocusing. At 3 and 5 months of age, 74% and 62% of the rats exhibited regular 4-day estrous cycles, respectively. This percentage had declined to 35% at 7 months and to 16% by 9 months of age. The marked decline in the incidence of 4-day cycles between 5 and 7 months was accompanied by an increased incidence of 5- to 7-day cycles, while by 9 months of age, 38% of the rats exhibited persistent vaginal cornification. In comparison to 3-month-old rats, plasma FSH levels were higher in 5- month-old rats at 1400 h on P and 1600 h on E. By 7 months, not only were plasma FSH levels increased further at these times, but they also were increased at 0600 and 1000 h on E during the secondary FSH surge. By 9 months, the preovulatory FSH surge appeared to be delayed, and the characteristic biphasic elevation in FSH levels on P and E was absent. In contrast to FSH, no change in the profile of plasma LH levels occurred until 9 months, when there was a marked reduction in the magnitude of the preovulatory LH surge. PRL levels were not consistently altered with age. In addition to the increase in FSH secretion observed in 5-month-old rats, the APs from these and older rats contained a higher proportion of acidic FSH forms than the APs from 3-month-old rats. These results demonstrate that alterations in FSH synthesis and release are early events associated with the aging process in rats, preceding the lengthening of estrous cycles observed between 5 and 7 months. Furthermore, perturbations in the regulation of FSH secretion during the secondary FSH surge precede impairments in the neuroendocrine mechanisms regulating the preovulatory discharge of LH and FSH. We postulate that the early (5 months of age) changes in FSH secretion and production may be due to an alteration in a specific feedback signal(s) from the ovary as a consequence of the aging process. (Endocrinology118: 1127–1133, 1986)