Hapon M B, Simoncini M, Via G, Jahn G A
Laboratorio de Reproducción y Lactancia, IMBECU, CRICYT-CONICET, 5500 Mendoza, Argentina.
Reproduction. 2003 Sep;126(3):371-82. doi: 10.1530/rep.0.1260371.
Thyroid dysfunctions can produce reproductive problems. Untreated maternal hypothyroidism has serious consequences on development of offspring, resulting in stunted growth and mental retardation. The effects of propylthiouracyl-induced hypothyroidism (0.1 g l(-1) in drinking water starting 8 days before mating, or given to virgin rats for 30 or 50 days) on the serum profiles of hormones related to reproduction and mammary function (prolactin, growth hormone (GH), progesterone, corticosterone, oestradiol, insulin-like growth factor I (IGF-I), thyroid-stimulating hormone (TSH), triiodothyronine and tetraiodothyronine), and on mammary function in virgin, pregnant and lactating rats, were investigated. Propylthiouracyl treatment severely decreased circulating triiodothyronine and tetraiodothyronine concentrations, and increased serum TSH concentrations. Virgin rats showed prolonged periods of vaginal dioestrus, increased circulating progesterone concentrations and afternoon peaks of prolactin concentration, which are indicative of prolactin-induced pseudopregnancy. Propylthiouracyl-treated virgin rats had mammary development comparable to that of midpregnancy, and half of these rats had increased mammary casein and lactose concentrations. Serum prolactin concentrations were decreased on the afternoon of day 5 of pregnancy, increased during late pregnancy (days 15-21) and were normal during lactation. Circulating GH concentrations decreased on days 15-21 of pregnancy, whereas progesterone concentrations increased during late pregnancy and early lactation. Circulating oestradiol (measured in late pregnancy and in virgin rats), IGF-I and corticosterone concentrations were decreased. Although assessment of mammary histology showed no differences in extent of development, casein content was increased in propylthiouracyl-treated rats on day 21 of pregnancy; litter growth was severely reduced and at day 20 of age the pups were hypothyroid, with decreased GH serum concentrations. An acute suckling experiment was performed on days 10-12 of lactation to determine whether some impairment in mammary function or the suckling reflex might account for these differences. After an 8 h separation of mothers from their litters and 30 min of suckling, circulating prolactin values were not affected by propylthiouracyl treatment, but serum oxytocin concentration and milk excretion were reduced. In conclusion, hypothyroidism induces various alterations in the hormone profiles of virgin and pregnant rats, and induces pseudopregnancies and mammary development in virgin rats. These alterations do not appear to have an overt impact on the outcome of pregnancy and on mammary function during lactation, with the exception of the milk ejection reflex, which may account at least partially for the reduced litter growth.
甲状腺功能障碍可导致生殖问题。未经治疗的母体甲状腺功能减退会对后代发育产生严重后果，导致生长发育迟缓及智力发育迟缓。研究了丙硫氧嘧啶诱导的甲状腺功能减退（在交配前8天开始，饮用水中含0.1 g l(-1)，或给予未孕大鼠30天或50天）对与生殖和乳腺功能相关的激素血清水平（催乳素、生长激素（GH）、孕酮、皮质酮、雌二醇、胰岛素样生长因子I（IGF-I）、促甲状腺激素（TSH）、三碘甲状腺原氨酸和四碘甲状腺原氨酸）的影响，以及对未孕、怀孕和哺乳大鼠乳腺功能的影响。丙硫氧嘧啶治疗严重降低了循环中三碘甲状腺原氨酸和四碘甲状腺原氨酸的浓度，并增加了血清TSH浓度。未孕大鼠出现阴道双期延长、循环孕酮浓度增加以及催乳素浓度午后峰值，这表明是催乳素诱导的假孕。经丙硫氧嘧啶处理的未孕大鼠乳腺发育与妊娠中期相当，其中一半大鼠乳腺酪蛋白和乳糖浓度增加。妊娠第5天下午血清催乳素浓度降低，妊娠后期（第15 - 21天）升高，哺乳期正常。妊娠第15 - 21天循环GH浓度降低，而孕酮浓度在妊娠后期和哺乳初期升高。循环雌二醇（在妊娠后期和未孕大鼠中测量）、IGF-I和皮质酮浓度降低。尽管乳腺组织学评估显示发育程度无差异，但在妊娠第21天，丙硫氧嘧啶处理的大鼠酪蛋白含量增加；窝仔生长严重减少，在20日龄时幼崽甲状腺功能减退，血清GH浓度降低。在哺乳期第10 - 12天进行了一项急性哺乳实验，以确定乳腺功能或哺乳反射的某些损害是否可能解释这些差异。在母亲与窝仔分离8小时并哺乳30分钟后，循环催乳素值不受丙硫氧嘧啶处理的影响，但血清催产素浓度和乳汁分泌减少。总之，甲状腺功能减退会引起未孕和怀孕大鼠激素水平的各种改变，并诱导未孕大鼠假孕和乳腺发育。这些改变似乎对妊娠结局和哺乳期间的乳腺功能没有明显影响，但乳汁排出反射除外，这可能至少部分解释了窝仔生长减少的原因。
