The episodic secretory pattern of growth hormone regulates liver carbonic anhydrase III. Studies in normal and mutant growth-hormone-deficient dwarf rats.
The episodic secretory pattern of growth hormone regulates liver carbonic anhydrase III. Studies in normal and mutant growth-hormone-deficient dwarf rats.
复制标题
生长激素的间歇性分泌模式调节肝脏碳酸酐酶 III。
作者：
S. Jeffery;N. Carter;R. Clark;I. Robinson
碳酸酐酶 III (CAIII) 在雄性大鼠肝脏中的浓度是雌性大鼠肝脏的 20 倍，并且对生长激素 (GH) 的释放模式敏感。雄性会间歇性地释放 GH，并具有高浓度的 CAIII；女性以更连续的方式产生 GH，并且 CAIII 水平较低。在正常雌性大鼠中，通过定期注射 GH 释放因子 (GRF) 或间歇性输注生长抑素（90 分钟开启/90 分钟关闭），内源 GH 分泌模式被男性化。两种治疗均诱导规律的 GH 脉冲并刺激生长，但只有间歇性生长抑素输注可提高 CAIII 水平（对照，1.5 +/- 0.5；生长抑素治疗，9.0 +/- 2.9 微克/毫克；平均值 +/- S.D.）。然而，GRF 脉冲（每 4 小时 4 微克）并没有提高 CAIII 水平（对照为 1.8 +/- 0.5；GRF 处理为 1.4 +/- 0.4 微克/毫克）。令人惊讶的是，在 GH 缺乏的侏儒大鼠品系中，肝脏 CAIII 也具有性别二态性（雄性，18.8 +/- 3；雌性，2.22 +/- 0.4 微克/毫克），其血浆 GH 水平较低，没有 3 小时 GH 峰值。雌性侏儒大鼠间歇性注射生长抑素可使肝脏 CAIII 部分男性化，与 GRF 共同注射可降低这种效应。这种 CAIII 反应并不是生长诱导的继发反应，因为生长抑素和 GRF 都不会刺激侏儒大鼠的生长，并且外源 GH 脉冲刺激雌性侏儒大鼠的生长，但不会使 CAIII 水平男性化。此外，雄性侏儒大鼠的连续GH输注使肝脏CAIII水平部分女性化（至9.1+/-2.4微克/毫克），而输注胰岛素样生长因子-1（诱导相同的体重增加）并不影响肝脏CAIII（20.8+/-6微克/毫克）。这些结果表明，肝脏 CAIII 表达对内源 GH 分泌模式高度敏感，与生长无关。它们还暗示脉冲之间的低基础 GH 水平，而不是峰值 GH 水平，是大鼠中性别二态性肝脏 CAIII 表达的主要决定因素。
Carbonic anhydrase III (CAIII) occurs in male rat liver at concentrations twenty times those in the female, and is sensitive to the pattern of growth hormone (GH) release. Males release GH episodically and have high concentrations of CAIII; females produce GH in a more continuous fashion and have lower CAIII levels. In normal female rats, the endogenous GH secretory pattern was masculinized, either by regular injections of GH-releasing factor (GRF) or by intermittent infusions of somatostatin (90 min on/90 min off). Both treatments induced regular GH pulses and stimulated growth, but only intermittent somatostatin infusions raised CAIII levels (controls, 1.5 +/- 0.5; somatostatin-treated, 9.0 +/- 2.9 micrograms/mg; means +/- S.D.). GRF pulses (4 micrograms every 4 h) did not however raise CAIII levels (controls 1.8 +/- 0.5; GRF-treated 1.4 +/- 0.4 micrograms/mg). Surprisingly, hepatic CAIII is also sexually dimorphic (males, 18.8 +/- 3; females, 2.22 +/- 0.4 micrograms/mg) in a GH-deficient dwarf rat strain which has low plasma GH levels without 3-hourly GH peaks. Intermittent somatostatin infusions in female dwarf rats partially masculinized hepatic CAIII, an effect reduced by co-infusion with GRF. This CAIII response was not secondary to growth induction, since neither somatostatin nor GRF stimulated growth in dwarf rats, and pulses of exogenous GH stimulated growth in female dwarfs without masculinizing CAIII levels. Furthermore, continuous GH infusion in male dwarf rats partially feminized hepatic CAIII levels (to 9.1 +/- 2.4 micrograms/mg), whereas infusions of insulin-like growth factor-1, which induced the same body weight gain, did not affect hepatic CAIII (20.8 +/- 6 micrograms/mg). These results show that hepatic CAIII expression is highly sensitive to the endogenous GH secretory pattern, independent of growth. They also implicate the low basal GH levels between pulses, rather than the peak GH levels, as the primary determinant of the sexually dimorphic hepatic CAIII expression in the rat.