Circadian alterations in prolactin, corticosterone, and thyroid hormone levels and down-regulation of prolactin receptor activity by 2,3,7,8-tetrachlorodibenzo- p-dioxin

Abstract

Studies were initiated to determine whether 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) affects circadian rhythms of serum prolactin (PRL), corticosterone, thyroxine (T 4), and triiodothyronine (T 3) in male Sprague-Dawley rats. In addition, the effects of TCDD on PRL receptor activity, as assessed by the ability of PRL to induce ornithine decarboxylase (ODC), were determined. The earliest effect detected following TCDD administration was a significant decrease in the serum PRL concentration compared with that of pair-fed controls within 4 hr ( p < 0.05). This was followed by a significant decrease in serum T 4 by 6 hr ( p < 0.05). By 8 hr the serum peak of corticosterone was shifted to 2 hr later in the TCDD-treated rats. This temporal sequence of hormonal changes suggests that the earlier alteration in PRL may be involved in the later alterations in the concentrations of serum T 4 and corticosterone. The serum PRL concentration 7 days after TCDD administration was significantly higher ( p < 0.05) in TCDD-treated animals compared with that in pair-fed controls (mean of 20.5 ± 3.7 vs 13.6 ± 18 ng/ml serum, p < 0.05, respectively). The elevation of ODC activity in response to PRL, 2 days after TCDD, was decreased in the order of thymus > adrenal > spleen > heart > kidney > liver. By 7 days, liver ODC activity in response to PRL was only 12% that detected in pair-fed controls. Liver ODC activity in response to dexamethasone and aminophylline was decreased to 25 and 22% of pair-fed controls, respectively, by 7 days after TCDD administration. However, in kidney, TCDD-treated rats had an increased ODC response to aminophylline to 191% of pair-fed controls by Day 7. These results suggest that the ability of TCDD to alter receptor coupling or the receptor number for diverse hormones may play a role in TCDD toxicity.