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The corticotrophin-releasing factor system is well characterized, and has been implicated in the control of pituitary functions in a number of animal models. In the female rat, the main effect of estrogens on the CRF system is down-regulation of immunoreactive CRF (i-CRF) and CRF receptor (CRF-R) in the anterior pituitary. The present study was undertaken to determine whether this down-regulation of the CRF system of i-CRF and CRF-R was associated with compensatory or adaptive changes in other parts of the brain involved in the control of the HPA axis. In order to achieve down-regulation of the pituitary CRF system, ovariectomized Sprague-Dawley female rats were implanted with slow-release subcutaneous implants containing estradiol-17beta. Six weeks after implantation, they received a single intraperitoneal injection of 5-hydroxytryptophan (5-HTP, 50 mg/kg), and were then killed by decapitation for CRF radioimmunoassay (RIA) and quantitative autoradiography. Levels of i-CRF, as measured by RIA, were significantly reduced in the anterior pituitary; however, in the paraventricular nucleus (PVN) of the hypothalamus i-CRF was increased, while in the external zone of the median eminence (ME) i-CRF was decreased. CRF-R binding in the hippocampus was increased, while binding in the PVN was decreased. Changes in i-CRF and CRF-R binding in the PVN were significantly correlated with those in the ME. In all of the hypothalamic areas studied, i-CRF binding was increased in 5-HTP-treated rats compared to control
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