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 μg/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 α-fetoprotein decreased markedly between days 12-28, and both normal and implant-produced serum E₂ levels parallel the decline in the protein titers. However, calculation of the total E₂ binding capacity of α-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 hr 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 mechanisms; phase III, which is initiated at the beginning of the juvenile period (~days 20-22) and in which the LH surge 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.