Testosterone is required for corticosteroid-binding globulin upregulation by morphine to be fully manifested

We previously reported that morphine increases the concentration of cortico steroid-binding globulin (CBG) in blood of male, but not female, rats. This pronounced sexual dimorphism suggested that CBG upregulation by morphine m ight be androgen-dependent. In the current studies, we found that castratio n, whether performed just before or just after puberty or in adulthood, inc reased the concentration of CBG in adult male rats. Naltrexone did not prev ent this increase and, therefore, it does not appear to be attributable to the release of endogenous opioids. Exposure to morphine for 1 week in adult hood increased (approximate to 100%) the concentration of CBG in intact, i. e., sham-castrated, males. The CBG levels of castrated rats treated with mo rphine did not differ from those of intact rats treated with morphine. Howe ver, because castration increased the concentration of CBG, the difference between the placebo and morphine groups decreased with time after castratio n. At 4 weeks after castration, the difference between the morphine and pla cebo groups (19%) was no longer statistically significant. Testosterone rep lacement prevented the rise in CBG levels following castration and maintain ed the magnitude of the difference between placebo and morphine-treated rat s within the normal range. Thus, testosterone appears necessary for morphin e effects on CBG to be fully manifested. (C) 2000 Elsevier Science Inc. All rights reserved.