EFFECT OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) ON PLASMA AND TISSUE BETA-ENDORPHIN-LIKE IMMUNOREACTIVITY IN THE MOST TCDD-SUSCEPTIBLEAND THE MOST TCDD-RESISTANT RAT STRAIN

The salient sign of acutely lethal 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication in rats is hypophagia along with a prominent body weight loss. Endogenous opiod peptides have been implicated as modula tors of food intake. In the present study, female rats of both the mos t TCDD-susceptible (Long-Evans [L-E]; LD50 9.8 mug/kg) and the most TC DD-resistant strain (Han/Wistar [H/W]; LD50 >7200 mug/kg) were exposed to a single dose of 50 mug/kg TCDD ip. This treatment is usually leth al within 1-6 weeks to all L-E rats and nonlethal to all H/W rats. The animals were killed at 1, 4 or 10 days after the treatment. Beta-Endo rphin-like immunoreactivity (beta-END-LI) was determined by a validate d RIA method in the hypothalamus, pituitary, pancreas, duodenum and pl asma. TCDD decreased plasma beta-END-LI concentration by 24-37% at eve ry time point of measurement in L-E rats alone. By contrast, feed-rest ricted controls exhibited an increase of similar magnitude on day 4. P ancreatic beta-END-LI was also elevated in feed-restricted controls at that time point as compared with either the ad libitum control or TCD D group. TCDD appeared to shrink the pituitary gland in both strains b y day 4. Pituitary weight was similarly lowered in TCDD-treated rats a nd feed-restricted controls at the last time point and this reduction was reflected in pituitary beta-END-LI content. Thus, TCDD affects sel ectively plasma beta-END-LI levels and this impact correlates with its lethality in these strains.