Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706-1102, USA.
J Physiol. 2011 Jan 15;589(Pt 2):409-21. doi: 10.1113/jphysiol.2010.198200. Epub 2010 Nov 15.
Steroidal sex hormones play an important role in the neural control of breathing. Previous studies in our laboratory have shown that gonadectomy in young male rats (3 months) eliminates a form of respiratory plasticity induced by intermittent hypoxia, known as long term facilitation (LTF). Testosterone replenishment restores LTF in gonadectomized male rats, and this is dependent on the conversion of testosterone to oestradiol by aromatase. By middle age (12 months), male rats no longer exhibit LTF of hypoglossal motor output; phrenic LTF is significantly reduced, and this persists into old age. We tested the hypothesis that LTF can be restored in old male rats by administration of testosterone. Intact Fischer 344 rats (>20 months) were implanted with Silastic tubing containing testosterone (T), T plus an aromatase inhibitor (T+ADT), or 5α-dihydrotestosterone (DHT), a form of testosterone not converted to oestradiol. One week post-surgery, LTF of hypoglossal and phrenic motor output was measured. By comparison with control rats, hypoglossal LTF was increased in testosterone-treated rats, with levels approaching that of normal young rats. LTF was not restored in T+ADT or DHT-treated rats. Aromatase levels in hypoglossal and phrenic nuclei did not change with age. As serum testosterone levels did not decline with age, local bioavailability of testosterone in old rats may be a limiting factor in the expression of this form of respiratory plasticity. Our findings suggest that testosterone supplementation could potentially be used to enhance upper airway control in the elderly.
甾体性激素在呼吸的神经控制中起着重要作用。我们实验室的先前研究表明，年轻雄性大鼠（3 个月）的性腺切除术消除了间歇性低氧诱导的一种呼吸适应性，即长时程易化（LTF）。睾丸激素补充恢复了去势雄性大鼠的 LTF，这依赖于芳香酶将睾丸激素转化为雌二醇。到中年（12 个月）时，雄性大鼠不再表现出舌下神经运动输出的 LTF；膈神经 LTF 显著降低，并且这种现象持续到老年。我们检验了一个假设，即在老年雄性大鼠中通过给予睾丸激素是否可以恢复 LTF。完整的 Fischer 344 大鼠（>20 个月）被植入含有睾丸激素（T）、T 加芳香酶抑制剂（T+ADT）或 5α-二氢睾丸酮（DHT）的硅酮管，DHT 是一种不能转化为雌二醇的睾丸激素形式。手术后一周，测量舌下神经和膈神经运动输出的 LTF。与对照大鼠相比，睾丸激素处理的大鼠的舌下神经 LTF 增加，水平接近正常年轻大鼠。在 T+ADT 或 DHT 处理的大鼠中未恢复 LTF。下丘脑和膈神经核中的芳香酶水平随年龄变化而不变。由于血清睾丸激素水平随年龄增长而没有下降，因此老年大鼠局部生物利用的睾丸激素可能是表达这种呼吸适应性的一个限制因素。我们的发现表明，睾丸激素补充剂可能可用于增强老年人的上呼吸道控制。
