Role of the serum estrogen-binding protein in the control of tissue estradiol levels during postnatal development of the female rat.

The role of the serum estrogen-binding protein (EBP) in the control of tissue estradiol levels during postnatal development of the female rat was examined. The estradiol-binding capacity of serum from the 1-day-old rats far exceeded the physiological level of estradiol in serum. The binding capacity decreased exponentially during the first 5 weeks of life to reach the low adult level at about the time of vaginal opening on day 37. From these observations one would predict that EBP would bind estradiol in the serum of the neonate, thereby preventing tissue uptake of the hormone. As the levels of EBP decline with advancing age, there should be a corresponding shift in the distribution of estradiol from serum to tissues. We have taken in vivo and in vitro approaches to evaluate these proposals. Female rats of various ages (1 day to 1 yr old) were sacrificed 1 h after [3H]estradiol injection and the radioactivity in serum and tissues was determined. During the first 11 days of life, the concentration of [3H]estradiol in serum was greater than the concentration of this hormone in estrogen-sensitive (uterus) and insensitive (lung, cerebral cortex, and diaphragm) tissues. Tissue to serum ratios of [3H]estradiol increased progressively between 13-34 days and then plateaued at about the time of puberty (37 days of age) at levels which were 50- to 150-fold greater than those observed in the neonate. The increase in tissue to serum ratios of [3H]estradiol during postnatal development probably resulted from the decline in serum EBP, since injection of neonatal serum into 28-day-old rats reduced tissue to serum ratios of [3H]estradiol to levels which were similar to those observed in 16-day-old animals. To determine the effects of EBP on uterine uptake of estradiol in vitro, uteri from 21-day-old rats were incubated with [3H]estradiol and serum obtained from rats of various ages. As the concentration of serum EBP declined with advancing serum donor age, there was a corresponding increase in the uterine uptake of [3H]estradiol. These results suggest that the decline in EBP is responsible for the progressive increase in tissue to serum ratios of estradiol during the first 5 weeks of life. It is suggested that the increase in tissue to serum ratios of estradiol between days 13-37 postpartum is an important factor in the initiation of estrogenic events during postnatal sexual maturation in the female rat.