Kirby J D, Jetton A E, Cooke P S, Hess R A, Bunick D, Ackland J F, Turek F W, Schwartz N B
Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208.
Endocrinology. 1992 Aug;131(2):559-65. doi: 10.1210/endo.131.2.1639007.
Neonatal treatment with the reversible goitrogen 6-N-propyl-2-thiouracil (PTU) results in a near doubling of testicular size and a 25% increase in the efficiency of spermatogenesis, without affecting circulating testosterone (T) levels in adult rats. The objectives of the present study were to examine the effects of neonatal PTU treatment on the pattern of testicular growth and circulating levels of anterior pituitary (FSH, LH, PRL, GH, and TSH), gonadal [immunoreactive inhibin-alpha (irI alpha) and T], and thyroid (T3 and T4) hormones over the first 100 days of life. Treatment of rats with PTU from birth to 24 days of age significantly reduced testicular weights between 10 and 60 days of age. However, the duration of testicular growth was extended in treated males, resulting in a 68% increase at 100 days of age. Serum gonadotropin levels in treated males were reduced throughout the experimental period, typically remaining between 50-70% of control levels. The characteristic robust prepubertal FSH peak was absent in PTU-treated males. Initially high until 20 days of age, irI alpha levels characteristically declined to adult levels (200-300 pg/ml) in control males. In treated males, irI alpha levels were reduced during the period of hypothyroidism, increased between 30 and 60 days, and then declined, but remained significantly higher (1.7- to 2-fold greater) than those observed in control males. Serum T levels were similar in treated and control males. Control males demonstrated increased T levels beginning at 45 days of age, earlier than observed in treated males; however, similar peak T levels were observed in all males. PTU treatment significantly suppressed serum GH and PRL and led to a 14-fold increase in circulating TSH during the period of treatment. However, unlike the gonadotropins, these hormones returned to control levels after PTU treatment, suggesting that the reduced levels of FSH and LH observed are not due to a generalized reduction in pituitary function. Serum T4 and T3 levels returned to control levels within 15 days after the removal of PTU. These results demonstrate that the neonatal PTU treatment-induced increases in adult testicular size and sperm production were not due to increased levels of FSH at any point in development. On the contrary, the observed increases occur in spite of chronically reduced FSH levels.
用可逆性致甲状腺肿物质6 - N - 丙基 - 2 - 硫氧嘧啶（PTU）对新生大鼠进行处理，会使成年大鼠睾丸大小几乎翻倍，精子发生效率提高25%，且不影响循环睾酮（T）水平。本研究的目的是检测新生期PTU处理对出生后100天内睾丸生长模式以及垂体前叶（促卵泡激素、促黄体生成素、催乳素、生长激素和促甲状腺激素）、性腺（免疫反应性抑制素α和T）和甲状腺（三碘甲状腺原氨酸和甲状腺素）激素循环水平的影响。从出生到24日龄用PTU处理大鼠，会显著降低10至60日龄大鼠的睾丸重量。然而，处理组雄性大鼠的睾丸生长持续时间延长，导致100日龄时睾丸重量增加68%。在整个实验期间，处理组雄性大鼠的血清促性腺激素水平均降低，通常维持在对照组水平的50 - 70%。PTU处理的雄性大鼠没有青春期前典型的促卵泡激素高峰。在对照组雄性大鼠中，免疫反应性抑制素α水平在20日龄前一直较高，之后会降至成年水平（200 - 300 pg/ml）。在处理组雄性大鼠中，免疫反应性抑制素α水平在甲状腺功能减退期间降低，在30至60日龄之间升高，然后下降，但仍显著高于对照组雄性大鼠（高1.7至2倍）。处理组和对照组雄性大鼠的血清T水平相似。对照组雄性大鼠从45日龄开始T水平升高，比处理组雄性大鼠更早；然而，所有雄性大鼠的T水平峰值相似。PTU处理显著抑制血清生长激素和催乳素，并在处理期间使循环促甲状腺激素增加14倍。然而，与促性腺激素不同的是，这些激素在PTU处理后恢复到对照水平，这表明观察到的促卵泡激素和促黄体生成素水平降低并非由于垂体功能普遍下降。在去除PTU后15天内，血清甲状腺素和三碘甲状腺原氨酸水平恢复到对照水平。这些结果表明，新生期PTU处理导致成年睾丸大小和精子生成增加并非由于发育过程中任何阶段促卵泡激素水平升高。相反，尽管促卵泡激素水平长期降低，但仍观察到了上述增加情况。
