Effects of gonadal steroids on clearance of growth hormone at steady state in the rat

Gonadal steroids have been implicated in the modulation of GH secretory patterns in the rat. We have studied the effects of testosterone (T) or estradiol (E2) on the steady state clearance (Clss) and plasma half-life (t1/2) of GH in male and female rats (n = 4-6/group). A femoral and a jugular cannula were surgically implanted into adult Sprague-Dawley rats. At the time of cannulation some rats were orchidectomized, and a Silastic capsule containing E2, T, or nothing was implanted sc. After recovery from surgery, either purified rat GH or a crude extract of rat pituitary was infused iv to attain steady state plasma GH concentrations. Blood samples were taken every 30 min for 4 h during the infusion, and nine samples were taken at 2.5-min intervals immediately after stopping the infusion. The mean Clss for GH in female rats were significantly (P less than or equal to 0.001) less than that in males, whereas the t1/2 did not differ between the two groups. Neither the Clss nor the t1/2 was affected by castration in males or females. The Clss of GH in E2-treated castrated males was significantly less (P less than 0.001) than that for intact males, but the t1/2 did not differ between the two groups. The Clss for GH was greater in T-treated ovariectomized rats than in intact females, but the t1/2 did not differ with T treatment. These results suggest that 1) the Clss for GH is lower in female rats than in males; 2) 4 weeks of gonadectomy has no effect on the Clss in males or females; 3) under experimental conditions, E2 decreases and T increases the Clss for GH; and 4) the t1/2 for GH is not different in males or females. The steroid-induced changes in Clss in the absence of detectable effects on t1/2 suggest that factors affecting the volume of distribution at steady state (i.e. plasma GH-binding proteins or GH heterogeneity) are involved in the effects of gonadal steroids on GH clearance in the rat.