Bagavandoss P, England B, Asirvatham A, Bruot B C
Department of Biological Sciences, Kent State University, Stark Campus, Canton, Ohio 44720, USA.
Proc Soc Exp Biol Med. 1998 Oct;219(1):77-84. doi: 10.3181/00379727-219-44319.
Hypothyroidism in the human female is often associated with ovarian follicular cysts and hyperandrogenism, two cardinal signs of polycystic ovary syndrome. To explore the intraovarian changes that lead to follicular cyst formation in hypothyroidism, we have created a prepubertal hypothyroid rat model. These hypothyroid rats are hyperandrogenic and develop transient ovarian follicular cysts. Hypothyroidism in newborn rats was induced by providing the lactating dams with 0.04% propylthiouracil (PTU)-containing water. Subsequently, female rats were weaned and kept on PTU-containing water. On Day 25 of age, the rats were primed with 15 international units of pregnant mare's serum gonadotropin (PMSG) in 100 microl of phosphate buffered saline. Two days later, to initiate pseudopregnancy, they were injected with five international units of human chorionic gonadotropin (hCG). The animals were sacrificed at appropriate times, and blood and ovaries were collected for analyses. Control experiments were done with euthyroid rats. Two days after PMSG injection, well-developed antral follicles were observed in both the hypothyroid and euthyroid rats. Two days after hCG injection, while the euthyroid rat ovaries, as expected, contained numerous corpora lutea (CL), the hypothyroid rat ovaries still retained antral follicles. Some of these follicles with degenerating oocytes showed signs of luteinization. By 3-4 days post-hCG injection, the hypothyroid rat ovaries developed cystic follicles. By Day 6, however, the hypothyroid rat ovaries were indistinguishable from those of the euthyroid rats. Although serum testosterone concentrations were significantly elevated in the hypothyroid rats on Days 1-3, progesterone concentrations were not significantly different from the euthyroid animals. However, by Days 8-14, the hypothyroid rats had significantly higher serum progesterone concentrations. This model will be useful for investigating the intraovarian biochemical changes that lead to follicular cyst development in response to acute gonadotropin treatment.
人类女性的甲状腺功能减退常与卵巢滤泡囊肿和高雄激素血症相关，这是多囊卵巢综合征的两个主要特征。为了探究导致甲状腺功能减退时滤泡囊肿形成的卵巢内变化，我们建立了青春期前甲状腺功能减退大鼠模型。这些甲状腺功能减退的大鼠具有高雄激素血症，并会出现短暂的卵巢滤泡囊肿。通过给哺乳期母鼠提供含0.04%丙硫氧嘧啶（PTU）的水来诱导新生大鼠甲状腺功能减退。随后，将雌性大鼠断奶并继续饮用含PTU的水。在25日龄时，给大鼠注射100微升磷酸盐缓冲盐水中含15国际单位的孕马血清促性腺激素（PMSG）进行预处理。两天后，为启动假孕，给它们注射5国际单位的人绒毛膜促性腺激素（hCG）。在适当的时候处死动物，收集血液和卵巢进行分析。用甲状腺功能正常的大鼠进行对照实验。注射PMSG两天后，在甲状腺功能减退和甲状腺功能正常的大鼠中均观察到发育良好的窦状卵泡。注射hCG两天后，正如预期的那样，甲状腺功能正常的大鼠卵巢中含有大量黄体（CL），而甲状腺功能减退的大鼠卵巢仍保留窦状卵泡。这些卵泡中一些卵母细胞退化的卵泡显示出黄体化迹象。到注射hCG后3 - 4天，甲状腺功能减退的大鼠卵巢形成囊性卵泡。然而，到第6天，甲状腺功能减退的大鼠卵巢与甲状腺功能正常的大鼠卵巢已无差异。虽然在第1 - 3天甲状腺功能减退的大鼠血清睾酮浓度显著升高，但孕酮浓度与甲状腺功能正常的动物无显著差异。然而，到第8 - 14天，甲状腺功能减退的大鼠血清孕酮浓度显著更高。该模型将有助于研究卵巢内生化变化，这些变化导致在急性促性腺激素治疗时滤泡囊肿的发展。
