Jeffery S, Carter N D, Clark R G, Robinson I C
Department of Child Health, St. George's Hospital Medical School, London, U.K.
Biochem J. 1990 Feb 15;266(1):69-74. doi: 10.1042/bj2660069.
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.
碳酸酐酶III（CAIII）在雄性大鼠肝脏中的浓度是雌性大鼠的20倍，并且对生长激素（GH）的释放模式敏感。雄性大鼠间歇性释放GH，CAIII浓度较高；雌性大鼠以更持续的方式分泌GH，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/90分钟关）可使内源性GH分泌模式雄性化。两种处理均诱导了规律性的GH脉冲并刺激了生长，但只有间歇性生长抑素输注提高了CAIII水平（对照组，1.5±0.5；生长抑素处理组，9.0±2.9微克/毫克；平均值±标准差）。然而，GRF脉冲（每4小时4微克）并未提高CAIII水平（对照组1.8±0.5；GRF处理组1.4±0.4微克/毫克）。令人惊讶的是，在一种GH缺乏的侏儒大鼠品系中，肝脏CAIII也存在性别差异（雄性，18.8±3；雌性，2.22±0.4微克/毫克），该品系血浆GH水平较低，且没有每3小时出现一次的GH峰值。在雌性侏儒大鼠中间歇性输注生长抑素可使肝脏CAIII部分雄性化，与GRF共同输注可减弱这种作用。这种CAIII反应并非生长诱导的继发结果，因为生长抑素和GRF均未刺激侏儒大鼠生长，而外源性GH脉冲刺激了雌性侏儒大鼠生长，但未使CAIII水平雄性化。此外，在雄性侏儒大鼠中持续输注GH可使肝脏CAIII水平部分雌性化（至9.1±2.4微克/毫克），而输注胰岛素样生长因子-1虽诱导了相同的体重增加，但并未影响肝脏CAIII（20.8±6微克/毫克）。这些结果表明，肝脏CAIII表达对内源性GH分泌模式高度敏感，与生长无关。它们还表明，脉冲之间的低基础GH水平而非GH峰值水平是大鼠肝脏CAIII性别差异表达的主要决定因素。
