Development of estradiol-positive feedback on luteinizing hormone release in the female rat: a quantitative study

Experiments were conducted to study, in a quantitative manner, the development of estradiol (E2)-positive feedback on LH release in the female rat. A Silastic capsule (20 mm in length/100 g BW) containing E2 dissolved in corn oil (400 micrograms/ml) reproduced first proestrous levels of serum E2 when implanted sc in juvenile rats of different ages (days 20-32). When similar capsules were implanted in infantile rats (days 10-18), serum E2, measured 2 days later, was found to be extremely elevated in 12- and 14-day-old rats (4-6 times higher than first proestrous levels), declining thereafter so that in 16- to 20-day-old rats the levels were only 2-fold greater than proestrous values. Serum levels of alpha-fetoprotein decreased markedly between days 12-28, and both normal and implant-produced serum E2 levels paralleled the decline in the protein titers. However, calculation of the total E2 binding capacity of alpha-fetoprotein indicated that in addition to binding to this protein, there are additional factors responsible for the persistence of E2 in the serum of infantile rats. A LH surge could not be induced in 12- or 14-day-old rats by a 48-h E2 pulse, despite the presence of substantial amounts of free E2, which exerted profound negative feedback effects. Between days 16-20, only E2 levels that were at least 2-fold higher than first proestrous values were effective in inducing a LH surge. Between days 22-34, a LH surge was elicited by serum E2 levels very similar to those seen during the first proestrus. By days 26-28, the profile of the LH surge was indistinguishable from that of the first preovulatory surge. Starting on day 26, and in addition to the LH surge elicited by the 48-h E2 pulse, an earlier surge occurred on the next day after E2 implantation. By day 30, the early LH surge became firmly established, and the late surge was no longer apparent. It is suggested that in the female rat, the development of E2-positive feedback comprises four phases: phase I, before day 16, in which the surge mechanism of the LH-releasing system is not developed; phase II, between days 16-20, in which E2 levels twice as high as those of first proestrus are necessary to activate the LH surge mechanism; phase III, which is initiated at the beginning of the juvenile period (approximately days 20-22) and in which the LH surge mechanism responds to E2 levels of preovulatory magnitude; and mechanism responds to E2 levels of preovulatory magnitude; and phase IV, which begins around days 26-28 and in which a 24-h exposure to E2 levels of preovulatory magnitude is sufficient to elicit a LH surge.