Painson J C, Veldhuis J D, Tannenbaum G S
Departments of Pediatrics and of Neurology and Neurosurgery, McGill University, and the Neuropeptide Physiology Laboratory, McGill University-Montreal Children's Hospital Research Institute, Montreal, Quebec H3H 1P3, Canada.
Am J Physiol Endocrinol Metab. 2000 May;278(5):E933-40. doi: 10.1152/ajpendo.2000.278.5.E933.
The neonatal gonadal steroid milieu is known to be important in imprinting the striking sexual dimorphism of growth hormone (GH) secretion; however, the influence of the sex steroids on GH control in adult life and their mechanism/site of action are largely unknown. In the present study, we tested the hypothesis that testosterone (T) subserves the gender-specific regularity of the GH release process in adulthood. The approximate entropy statistic (ApEn) was used to quantify the degree of regularity of GH release patterns over time. Eighteen hours after a single subcutaneous injection of 1 mg T, both sham-operated and ovariectomized (OVX) female adult rats displayed plasma GH profiles that were strikingly similar to the regular male-like ultradian rhythm of GH secretion. The highest ApEn values, denoting greater disorderliness of GH secretion, were observed in the ovary-intact group, and T injection significantly (P < 0.001) reduced this irregularity whether or not the ovaries were present. Serial intravenous injections of GH-releasing hormone (GHRH) caused a similar increase in plasma GH levels in sham-operated females independently of time of administration. In contrast, female rats administered T exhibited a male-like intermittent pattern of GH responsiveness to GHRH, the latter known to be due to the cyclic release of endogenous somatostatin. These results demonstrate that acute exposure to T during adult life can rapidly and profoundly "masculinize" GH pulse-generating circuits in the female rat. Our findings suggest that the enhanced orderliness characteristic of the GH release process in males, compared with females, is regulated by T. We postulate that this T-induced regularity is mediated at the level of the hypothalamus by inducing regularity in somatostatin secretion, which in turn governs overall GH periodicity.
已知新生儿性腺类固醇环境对于生长激素（GH）分泌显著的性别差异印记十分重要；然而，成年期性激素对GH调控的影响及其作用机制/作用位点在很大程度上尚不清楚。在本研究中，我们检验了睾酮（T）有助于成年期GH释放过程中性别特异性规律的这一假说。近似熵统计量（ApEn）用于量化GH释放模式随时间变化的规律程度。单次皮下注射1mg T后18小时，假手术组和去卵巢（OVX）成年雌性大鼠的血浆GH谱均与雄性样GH分泌的规则超日节律惊人地相似。在卵巢完整组中观察到最高的ApEn值，表明GH分泌的无序性更大，无论卵巢是否存在，T注射均显著（P < 0.001）降低了这种不规则性。连续静脉注射生长激素释放激素（GHRH）可使假手术雌性大鼠的血浆GH水平产生类似的升高，且与给药时间无关。相比之下，给予T的雌性大鼠对GHRH的GH反应呈现出雄性样的间歇性模式，后者已知是由于内源性生长抑素的周期性释放所致。这些结果表明，成年期急性暴露于T可迅速且深刻地使雌性大鼠的GH脉冲产生回路“雄性化”。我们的研究结果表明，与雌性相比，雄性GH释放过程中增强的有序性特征受T调节。我们推测，这种T诱导的规律性是通过诱导生长抑素分泌的规律性在下丘脑水平介导的，而生长抑素分泌的规律性又反过来控制整体GH的周期性。
