Geelhoed G W
George Washington University Medical Center, Washington, DC, USA.
Med Hypotheses. 1996 Dec;47(6):471-9. doi: 10.1016/s0306-9877(96)90160-7.
An old bull, it is said by those who know, can have his troubles. Included among these are vertebral osteosclerosis and ankylosing spondylosis; this stiffening up limits, rather than accentuates, the value and reproductive potential of a stud bull past his prime. Associated with these abnormalities, however-and not seen in age-matched cows of comparable breeds-are fascinating endocrine neoplasms suggestive of a pattern that could be productive as a model of human hereditary endocrine abnormalities. Adjacent to the thyroid gland in other vertebrates are ultimobranchial bodies that are incorporated into the lateral thyroid lobes in primates as the parafollicular "C cells' of the thyroid. These are the cells in man that give rise to medullary thyroid cancer and are associated with calcitonin secretion, useful as a tumor marker. In aging bulls of whatever breed, nearly half exhibit abnormality of these ultimobranchial bodies: 20% show hyperplasia, and 30% have frank neoplasia. These ultimobranchial tumors appear in bulls passing 6 1/2 years in age, and are absent in young bulls and all cows of any age. Calcitonin can be demonstrated in the ultimobranchial tumors from bulls, and secretion is stimulated by calcium infusion, though serum calcium remains normal. The ultimobranchial tumors themselves can range from hyperplasia through adenoma to metastasizing carcinoma-in fact, representing one of the commoner cattle cancers. Parathyroid glands taken from bulls with these ultimobranchial tumors initially show evidence of inhibited secretory activity and morphologic atrophy, but later go on to develop hyperplasia and, eventually, autonomy. Cattle forage on calcium-rich diets. Bulls appear to respond to this calcium excess from the positive balance, but breeding cows have the unique calcium deficits of the high net loss of calcium through lactation and the large requirements of calcifying a fetal skeleton. Chronic stimulation of the APUD-derived ultimobranchial bodies by high calcium intake, not counterbalanced by calcium losses in the bulls, may account for the development over time of the ultimobranchial neoplasms. Further, a number of the bulls who have the ultimobranchial tumors are found to have multiple endocrine tumors in other glands-bilateral pheochromocytomas and pituitary acidophil adenomas.
据说，上了年纪的公牛会有不少麻烦。其中包括脊椎骨硬化和强直性脊柱炎；这种身体僵硬会限制而非增强处于壮年后期种公牛的价值和繁殖潜力。然而，与这些异常情况相关的——在年龄相仿的同品种母牛中并未出现——是令人着迷的内分泌肿瘤，提示出一种模式，有可能成为人类遗传性内分泌异常的模型。在其他脊椎动物中，甲状腺附近有后鳃体，在灵长类动物中，后鳃体并入甲状腺侧叶，成为甲状腺的滤泡旁“C细胞”。这些细胞在人类中会引发甲状腺髓样癌，并与降钙素分泌有关，降钙素可用作肿瘤标志物。无论何种品种的老龄公牛，近半数都表现出这些后鳃体异常：20%表现为增生，30%有明显的肿瘤形成。这些后鳃体肿瘤出现在6岁半以上的公牛中，年轻公牛和任何年龄的母牛中均未出现。降钙素可在公牛的后鳃体肿瘤中检测到，静脉注射钙可刺激其分泌，尽管血清钙仍保持正常。后鳃体肿瘤本身范围从增生到腺瘤，再到转移性癌——实际上，它是较为常见的牛类癌症之一。取自患有这些后鳃体肿瘤公牛的甲状旁腺，最初显示出分泌活动受抑制和形态萎缩的迹象，但后来会发展为增生，并最终出现自主性。牛以富含钙的食物为食。公牛似乎能从这种正钙平衡状态下的钙过量中得到反应，但繁殖母牛却有独特的钙缺乏问题，即通过泌乳导致大量钙净流失，以及钙化胎儿骨骼的大量需求。公牛高钙摄入对源自APUD的后鳃体的长期刺激，且未被钙流失所抵消，这可能是后鳃体肿瘤随时间发展的原因。此外，发现一些患有后鳃体肿瘤的公牛在其他腺体中也有多发内分泌肿瘤——双侧嗜铬细胞瘤和垂体嗜酸性腺瘤。
