Effects of hyperandrogenemia and increased adiposity on reproductive and metabolic parameters in young adult female monkeys.
Effects of hyperandrogenemia and increased adiposity on reproductive and metabolic parameters in young adult female monkeys.
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DOI：
10.1152/ajpendo.00310.2013
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发表时间：
2014-06
期刊：
影响因子：
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通讯作者：
W. McGee;W. McGee;C. Bishop;C. R. Pohl;R. J. Chang;John C. Marshall;Francis K.-Y. Pau;R. Stouffer-R.-S
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文献类型：
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作者：
W. McGee;W. McGee;C. Bishop;C. R. Pohl;R. J. Chang;John C. Marshall;Francis K.-Y. Pau;R. Stouffer-R.-S
许多高雄激素血症患者超重或肥胖，这加剧了与多囊卵巢综合征(PCOS)相关的发病率。为了检测睾酮(T)产生PCOS样症状的能力，猴子从青春期前开始接受T或胆固醇(对照组)植入(n=6)。正如之前报道的那样，T处理的动物在5岁时增加了对生殖轴的神经内分泌驱动[增加了黄体生成素(LH)的脉冲频率]，而卵巢或代谢特征没有显著变化。为了检验T和肥胖的综合影响，在5.5岁(人类年龄相当：17岁)，猴子被放入典型的西方文化的高卡路里、高脂肪饮食[西式饮食(WSD)]，将体脂从WSD前的2%增加到15%-19%(14mo WSD)。给药6个月后，对照组的黄体生成素脉冲频率增加到T组动物的水平，而两组动物的黄体生成素脉冲幅度均降低并保持在较低水平。WSD组卵泡早期有腔卵泡数增加，但最大卵泡大小减少50%。在卵泡晚期，经T处理的雌性小卵泡数量多于对照。在月经周期的黄体期，接受T治疗的猴子的黄体酮水平也较低。虽然空腹胰岛素在不同组之间没有变化，但T处理的动物在服用WSD一年后降低了胰岛素敏感性。因此，虽然WSD单独摄入导致了PCOS的一些特征，但T+WSD导致了更严重的胰岛素不敏感表型，增加了周期中期有腔卵泡的数量，并降低了循环黄体期孕酮水平。
Many patients with hyperandrogenemia are overweight or obese, which exacerbates morbidities associated with polycystic ovary syndrome (PCOS). To examine the ability of testosterone (T) to generate PCOS-like symptoms, monkeys received T or cholesterol (control) implants (n = 6/group) beginning prepubertally. As previously reported, T-treated animals had increased neuroendocrine drive to the reproductive axis [increased luteinizing hormone (LH) pulse frequency] at 5 yr, without remarkable changes in ovarian or metabolic features. To examine the combined effects of T and obesity, at 5.5 yr (human equivalent age: 17 yr), monkeys were placed on a high-calorie, high-fat diet typical of Western cultures [Western style diet (WSD)], which increased body fat from <2% (pre-WSD) to 15-19% (14 mo WSD). By 6 mo on WSD, LH pulse frequency in the controls increased to that of T-treated animals, whereas LH pulse amplitude decreased in both groups and remained low. The numbers of antral follicles present during the early follicular phase increased in both groups on the WSD, but maximal follicular size decreased by 50%. During the late follicular phase, T-treated females had greater numbers of small antral follicles than controls. T-treated monkeys also had lower progesterone during the luteal phase of the menstrual cycle. Although fasting insulin did not vary between groups, T-treated animals had decreased insulin sensitivity after 1 yr on WSD. Thus, while WSD consumption alone led to some features characteristic of PCOS, T + WSD caused a more severe phenotype with regard to insulin insensitivity, increased numbers of antral follicles at midcycle, and decreased circulating luteal phase progesterone levels.