Gevers E F, Wit J M, Robinson I C
Division of Neurophysiology and Neuropharmacology, National Institute for Medical Research, Mill Hill, London, UK.
J Endocrinol. 1995 Apr;145(1):69-79. doi: 10.1677/joe.0.1450069.
Normal rats are sexually dimorphic in their growth and GH secretion. Gonadectomy (Gnx) changes the GH secretory pattern and this could explain differential growth rates in male and female rats. Gonadal steroids may also affect tissue growth directly, or by changing their responsiveness to GH. The effects of Gnx on growth, GH responsiveness, and hepatic GH receptors have now been studied in young (4-7 weeks old) GH-deficient dwarf rats in which the effects of steroid-induced alterations in residual endogenous GH secretion will be much less pronounced. Groups of intact and Gnx dwarf rats (n = 5-7) were infused with recombinant human GH (144 micrograms/day) either continuously or in a pulsatile pattern (every 3 h) for 7 days, whilst control groups received saline infusions. Gains in weight, length and tibial bone growth were measured. Female dwarf rats grew significantly more slowly than male dwarfs. Gnx in male dwarfs inhibited growth significantly, whereas ovariectomy had a lesser stimulatory effect in females. Hepatic lactogenic and somatogenic receptors were higher in females and ovariectomy lowered their values towards male levels. Pulsatile GH infusions were more effective than continuous infusions of the same daily GH dose, but when the different underlying growth rates (measured in saline-infused Gnx animals) were taken into account, the responsiveness to pulses of hGH was not different between males and females or between intact and Gnx animals. We have concluded that Gnx in dwarf rats does affect growth, but the effects are small in comparison with those seen in normal rats. Since pulsatile GH infusions stimulated growth more effectively than continuous GH, irrespective of the gonadal steroid status, and the responsiveness to exogenous GH was not changed by Gnx, the results imply that changes in the GH secretory pattern induced by gonadal steroids may have a larger impact on the growth rate than direct effects at the tissue level, at least in the rat.
正常大鼠在生长和生长激素(GH)分泌方面存在性别差异。去势(Gnx)会改变GH分泌模式,这可以解释雄性和雌性大鼠不同的生长速率。性腺类固醇也可能直接影响组织生长,或通过改变组织对GH的反应性来影响生长。现在已经在年轻(4 - 7周龄)的GH缺乏型侏儒大鼠中研究了Gnx对生长、GH反应性和肝脏GH受体的影响,在这些大鼠中,类固醇诱导的残余内源性GH分泌改变的影响要小得多。将完整和去势的侏儒大鼠组(n = 5 - 7)连续或以脉冲模式(每3小时一次)注入重组人生长激素(144微克/天),持续7天,而对照组接受生理盐水注入。测量体重、体长和胫骨骨生长的增加情况。雌性侏儒大鼠的生长明显比雄性侏儒大鼠慢。雄性侏儒大鼠去势显著抑制生长,而雌性大鼠卵巢切除的刺激作用较小。雌性大鼠肝脏中的催乳素和生长激素受体较高,卵巢切除后其值降至雄性水平。相同日GH剂量下,脉冲式GH注入比连续注入更有效,但考虑到不同的基础生长速率(在注入生理盐水的去势动物中测量),雄性和雌性之间或完整和去势动物之间对hGH脉冲的反应性没有差异。我们得出结论,侏儒大鼠去势确实会影响生长,但与正常大鼠相比,这种影响较小。由于无论性腺类固醇状态如何,脉冲式GH注入比连续GH注入更有效地刺激生长,并且去势不会改变对外源性GH的反应性,结果表明性腺类固醇诱导的GH分泌模式变化对生长速率的影响可能比在组织水平的直接影响更大,至少在大鼠中是这样。