Differential Sensitivity of Estrogen Target Tissues: The Role of the Receptor*

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Abstract
In this report, we describe the neuroendocrine features of the estrogen-implanted ovariectomized rat and define a number of estrogen-induced responses in these animals. We further demonstrate differential sensitivity to estradiol among several estrogen target tissues and investigate the role of the estrogen receptor in the mediation of this phenomenon. Ovariectomized rats implanted with a range of estradiol doses (1 μ-5 mg estradiol/capsule) provided a good experimental model for generation of dose response curves. These animals have serum estradiol levels that span the physiological range and that modulate numerous neuroendocrine endpoints. Using this animal model, dose response curves between estradiol and six estrogeninduced responses were generated. These responses included uterine wet and dry weight, negative and positive feedback of estrogen on serum LH levels, the LHRH content of neurosecretory terminals of the medial basal hypothalamus, and the size of the LHRH bolus released from the median eminence at lights off. These dose response curves fall into two groups: a high sensitivity category that includes the responses of the uterus and pituitary, and a lower sensitivity category that includes the hypothalamic responses. Thus the peripheral responses are more sensitive to estradiol than those of the central nervous system (CNS). In addition, injection of estradiol, estriol, and clomiphene (Clomid) as well as implantation of estradiol demonstrate that translocation of the estrogen receptor from the cytoplasmic to the nuclear compartment occurs at lower doses of estradiol in the periphery than in the CNS. Thus, we believe that the differential sensitivity of the responses of estrogen target tissues is due to differential estrogen receptor translocation. The lower CNS sensitivity may be due to the low concentrations of estradiol found in brain tissue. We suggest that these low concentrations are caused by exclusion of protein-bound serum estradiol from the CNS by the blood-brain barrier.

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