Kutzler Michelle Anne
Department of Animal and Rangeland Sciences, Oregon State University, 112 Withycombe Hall, Corvallis, OR, 97331, USA.
Theriogenology. 2023 Jan 15;196:270-274. doi: 10.1016/j.theriogenology.2022.11.007. Epub 2022 Nov 9.
Removal of the gonads with surgical sterilization results in a loss of negative feedback to the hypothalamus and anterior pituitary. The sustained supraphysiologic luteinizing hormone (LH) concentrations in gonadectomized dogs can significantly alter organ function and even induce neoplastic changes. For example, gonad removal has a profound effect on thyroid function and is reported to be the most significant cause for the development of hypothyroidism in dogs. Thirty percent more gonadectomized dogs develop hypothyroidism compared with intact dogs. Within the canine thyroid, LH receptors are co-localized with thyroid stimulating hormone (TSH) receptors. Continuous LH receptor activation in gonadectomized dogs may interfere TSH receptor function by consuming second messengers involved in G-protein receptor cell signaling, preventing the action of TSH when it binds to its receptor in the thyroid, resulting in hypothyroidism. The incidence of anterior cruciate ligament ruptures is significantly increased following gonad removal independent of breed, sex, weight or body condition. Luteinizing hormone receptors are expressed in the cruciate ligament and continuous LH receptor activation may increase laxity in these ligaments, resulting in joint instability. Both male and female gonadectomized dogs are at a significantly increased risk for lymphoma and hemangiosarcoma. Luteinizing hormone receptors are also abundant in these tissues. Research in four canine hemangiosarcoma cell lines found that LH receptor activation induces cell proliferation. In addition, research in three canine T-cell lymphoma cell lines found that LH receptor activation induces cell proliferation, adhesion, and invasion as well as increases LH receptor expression. Research is needed to determine if LH reducing strategies using gonadotropin releasing hormone agonists will increase remission times in gonadectomized dogs with LH receptor-positive tumors. In conclusion, among the non-reproductive functions of gonads, suppression of LH secretion and resulting LH receptor overexpression appear necessary in maintaining endocrine, musculoskeletal, and anti-neoplastic health.
通过手术绝育切除性腺会导致对下丘脑和垂体前叶的负反馈丧失。去势犬体内持续的超生理水平促黄体生成素（LH）浓度会显著改变器官功能，甚至诱发肿瘤变化。例如，性腺切除对甲状腺功能有深远影响，据报道是犬类甲状腺功能减退症发生的最主要原因。与未绝育犬相比，去势犬患甲状腺功能减退症的比例高出30%。在犬类甲状腺中，LH受体与促甲状腺激素（TSH）受体共定位。去势犬体内LH受体的持续激活可能会通过消耗参与G蛋白受体细胞信号传导的第二信使来干扰TSH受体功能，当TSH与甲状腺中的受体结合时阻止其作用，从而导致甲状腺功能减退。无论品种、性别、体重或身体状况如何，性腺切除后前交叉韧带断裂的发生率都会显著增加。LH受体在交叉韧带中表达，LH受体的持续激活可能会增加这些韧带的松弛度，导致关节不稳定。雄性和雌性去势犬患淋巴瘤和血管肉瘤的风险均显著增加。LH受体在这些组织中也很丰富。对四种犬血管肉瘤细胞系的研究发现，LH受体激活会诱导细胞增殖。此外，对三种犬T细胞淋巴瘤细胞系的研究发现，LH受体激活会诱导细胞增殖、黏附、侵袭，并增加LH受体表达。需要进行研究以确定使用促性腺激素释放激素激动剂降低LH的策略是否会延长LH受体阳性肿瘤去势犬的缓解期。总之，在性腺的非生殖功能中，抑制LH分泌以及由此导致的LH受体过表达似乎对维持内分泌、肌肉骨骼和抗肿瘤健康是必要的。
