Department of Dairy Science, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Biol Reprod. 2013 Jun 20;88(6):153. doi: 10.1095/biolreprod.113.107862. Print 2013 Jun.
Polycystic ovarian syndrome (PCOS) is characterized by hyperandrogenemia, polycystic ovaries, and menstrual disturbance and a clear association with insulin resistance. This research evaluated whether induction of insulin resistance, using dexamethasone (DEX), in a monovular animal model, the cow, could produce an ovarian phenotype similar to PCOS. In all of these experiments, DEX induced insulin resistance in cows as shown by increased glucose, insulin, and HOMA-IR (homeostasis model assessment of insulin resistance). Experiment 1: DEX induced anovulation (zero of five DEX vs. four of four control cows ovulated) and decreased circulating estradiol (E2). Experiment 2: Gonadotropin-releasing hormone (GnRH) was administered to determine pituitary and follicular responses during insulin resistance. GnRH induced a luteinizing hormone (LH) surge and ovulation in both DEX (seven of seven) and control (seven of seven) cows. Experiment 3: E2 was administered to determine hypothalamic responsiveness after induction of an E2 surge in DEX (eight of eight) and control (eight of eight) cows. An LH surge was induced in control (eight of eight) but not DEX (zero of eight) cows. All control (eight of eight) but only two of eight DEX cows ovulated within 60 h of E2 administration. Experiment 4: Short-term DEX was initiated 24 h after induced luteal regression to determine if DEX could acutely block ovulation before peak insulin resistance was induced, similar to progesterone (P4). All control (five of five), no P4-treated (zero of six), and 50% of DEX-treated (three of six) cows ovulated by 96 h after luteal regression. All anovular cows had reduced circulating E2. These data are consistent with DEX creating a lesion in hypothalamic positive feedback to E2 without altering pituitary responsiveness to GnRH or ovulatory responsiveness of follicles to LH. It remains to be determined if the considerable insulin resistance and the reduced follicular E2 production induced by DEX had any physiological importance in the induction of anovulation.
多囊卵巢综合征（PCOS）的特征是高雄激素血症、多囊卵巢和月经紊乱，并与胰岛素抵抗有明确的关联。本研究评估了在单胎动物模型——奶牛中诱导胰岛素抵抗（使用地塞米松（DEX））是否能产生类似于 PCOS 的卵巢表型。在所有这些实验中，DEX 诱导奶牛发生胰岛素抵抗，表现为血糖、胰岛素和 HOMA-IR（胰岛素抵抗的稳态模型评估）增加。实验 1：DEX 引起排卵障碍（5 只 DEX 牛中无排卵，4 只对照牛排卵），并降低循环雌二醇（E2）。实验 2：给予促性腺激素释放激素（GnRH）以确定胰岛素抵抗期间垂体和卵泡的反应。GnRH 在 DEX（7/7）和对照（7/7）牛中均诱导黄体生成素（LH）峰和排卵。实验 3：给予雌二醇以确定在 DEX（8/8）和对照（8/8）牛中诱导 E2 峰后的下丘脑反应。在对照（8/8）牛中诱导 LH 峰，但在 DEX（8/8）牛中未诱导。所有对照（8/8）牛均排卵，但仅 8 只 DEX 牛中的 2 只在 E2 给药后 60 小时内排卵。实验 4：在诱导黄体消退后 24 小时开始短期 DEX，以确定 DEX 是否可以在诱导高峰胰岛素抵抗之前急性阻断排卵，类似于孕酮（P4）。所有对照（5/5）、无 P4 处理（6/6）和 50%DEX 处理（6/6）牛在黄体消退后 96 小时排卵。所有无排卵牛的循环 E2 减少。这些数据表明，DEX 导致下丘脑对 E2 的正反馈出现损伤，而不改变垂体对 GnRH 的反应或卵泡对 LH 的排卵反应。尚需确定 DEX 诱导的胰岛素抵抗和卵泡 E2 产生减少是否对排卵障碍的诱导具有任何生理意义。
