Badger T M, Millard W J, Owens S M, LaRovere J, O'Sullivan D
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock 72205.
Endocrinology. 1991 Feb;128(2):1065-72. doi: 10.1210/endo-128-2-1065.
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.
性腺类固醇被认为参与调节大鼠生长激素（GH）的分泌模式。我们研究了睾酮（T）或雌二醇（E2）对雄性和雌性大鼠（每组n = 4 - 6只）GH的稳态清除率（Clss）和血浆半衰期（t1/2）的影响。将一根股静脉插管和一根颈静脉插管通过手术植入成年Sprague-Dawley大鼠体内。插管时，对部分大鼠进行去势手术，并在皮下植入含E2、T或不含任何物质的硅橡胶胶囊。手术后恢复后，通过静脉输注纯化的大鼠GH或大鼠垂体粗提物以达到稳态血浆GH浓度。在输注过程中，每30分钟采集一次血样，共采集4小时，停止输注后立即以2.5分钟的间隔采集9个血样。雌性大鼠GH的平均Clss显著低于雄性大鼠（P≤0.001），而两组之间的t1/2没有差异。无论雄性还是雌性，去势对Clss和t1/2均无影响。用E2处理的去势雄性大鼠GH的Clss显著低于完整雄性大鼠（P＜0.001），但两组之间的t1/2没有差异。用T处理的去卵巢大鼠GH的Clss高于完整雌性大鼠，但t1/2不受T处理的影响。这些结果表明：1）雌性大鼠GH的Clss低于雄性大鼠；2）四周的性腺切除对雄性或雌性大鼠的Clss没有影响；3）在实验条件下，E2降低而T增加GH的Clss；4）雄性和雌性大鼠GH的t1/2没有差异。在未检测到对t1/2有影响的情况下，类固醇诱导的Clss变化表明，影响稳态分布容积的因素（即血浆GH结合蛋白或GH异质性）参与了性腺类固醇对大鼠GH清除率的影响。
