Department of Animal Morphology and Physiology, Faculty of Agricultural and Veterinarian Sciences, São Paulo State University, Jaboticabal, São Paulo, Brazil.
Brain & Breathing Science Laboratory, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Canada.
J Endocrinol. 2020 Oct;247(1):101-114. doi: 10.1530/JOE-20-0257.
Many diseases of the respiratory system occur differently in males and females, indicating a possible role of gonadal hormones in respiratory control. We hypothesized that testosterone (T) is important for the ventilatory chemosensitivity responses in males. To test this hypothesis, we evaluated ventilation (V̇ E), metabolic rate and body temperature (Tb) under normoxia/normocapnia, hypercapnia and hypoxia in orchiectomized (ORX), ORX with testosterone replacement (ORX + T) or flutamide (FL, androgen receptor blocker)-treated rats. We also performed immunohistochemistry to evaluate the presence of androgen receptor (AR) in the carotid body (CB) of intact males. Orchiectomy promoted a reduction V̇ E and ventilatory equivalent (V̇ E /V̇ O2) under room-air conditions, which was restored with testosterone treatment. Moreover, during hypoxia or hypercapnia, animals that received testosterone replacement had a higher V̇ E and V̇ E /V̇ O2 than control and ORX, without changes in metabolic and thermal variables. Flutamide decreased the hypoxic ventilatory response without changing the CO2-drive to breathe, suggesting that the testosterone effect on hypercapnic hyperventilation does not appear to involve the AR. We also determined the presence of AR in the CB of intact animals. Our findings demonstrate that testosterone seems to be important for maintaining resting V̇ E in males. In addition, the influence of testosterone on V̇ E, either during resting conditions or under hypoxia and hypercapnia, seems to be a direct and specific effect, as no changes in metabolic rate or Tb were observed during any treatment. Finally, a putative site of testosterone action during hypoxia is the CB, since we detected the presence of AR in this structure.
许多呼吸系统疾病在男性和女性中的表现不同，这表明性腺激素在呼吸控制中可能发挥作用。我们假设睾丸酮（T）对男性通气化学敏感性反应很重要。为了验证这一假设，我们评估了去势（ORX）、去势加睾丸酮替代（ORX+T）或氟他胺（FL，雄激素受体阻滞剂）处理的大鼠在常氧/常碳酸血症、高碳酸血症和低氧条件下的通气（VE）、代谢率和体温（Tb）。我们还进行了免疫组织化学评估，以评估完整雄性动物颈动脉体（CB）中雄激素受体（AR）的存在。去势导致在常气条件下 VE 和通气当量（VE/V̇O2）降低，而用睾丸酮处理则恢复。此外，在低氧或高碳酸血症期间，接受睾丸酮替代治疗的动物的 VE 和 VE/V̇O2 高于对照和 ORX，而代谢和热变量没有变化。氟他胺降低了低氧通气反应，而不改变 CO2 驱动呼吸，这表明睾丸酮对高碳酸血症性通气过度的影响似乎不涉及 AR。我们还确定了完整动物 CB 中 AR 的存在。我们的研究结果表明，睾丸酮似乎对维持男性静息 VE 很重要。此外，睾丸酮对 VE 的影响，无论是在静息状态下还是在低氧和高碳酸血症下，似乎都是一种直接和特定的影响，因为在任何治疗期间代谢率或 Tb 都没有变化。最后，CB 可能是睾丸酮在低氧条件下作用的部位，因为我们在该结构中检测到了 AR 的存在。
