Welt Corrine K, Taylor Ann E, Martin Kathryn A, Hall Janet E
Reproductive Endocrine Unit and the National Center for Infertility Research, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
J Clin Endocrinol Metab. 2002 Dec;87(12):5559-65. doi: 10.1210/jc.2002-020546.
Inhibin B is a product of the granulosa cells of growing preantral and antral follicles. Despite the large ovarian volume and increased follicle number typically detected in women with polycystic ovary syndrome (PCOS), previous studies demonstrate that inhibin B is not elevated as would be expected in PCOS, but is inversely correlated with body mass index (BMI). We therefore hypothesized that inhibin B levels in women with PCOS are regulated by a factor related to BMI. Thus, LH, sex steroids, and metabolic parameters were measured in 50 anovulatory PCOS subjects in pools constituted from equal aliquots of serum drawn every 10 min for 4 h and were correlated with inhibin B. Based on the results of these correlative studies, inhibin B regulation by human chorionic gonadotropin (hCG) and insulin was tested directly. In PCOS subjects, inhibin B correlated inversely with BMI (r = -0.413; P < 0.004) and fasting insulin (r = -0.409; P < 0.004). Inhibin B also correlated directly with pool LH (r = 0.419; P < 0.003), LH pulse amplitude (r = 0.512; P < 0.0001), and SHBG (r = 0.429; P < 0.003). The relationships demonstrated for inhibin B were not demonstrated for inhibin A, nor were they evident in normal subjects. To determine whether the correlations represent regulation of inhibin B, i.e. stimulation of inhibin B by LH or suppression by insulin, two interventional studies were performed. In the first study hCG (5000 U) was administered to PCOS subjects (n = 15) to mimic the effects of LH. Inhibin B was not increased, but was significantly reduced 24 h after hCG administration (223.8 +/- 21.3 vs. 152.4 +/- 15.9 pg/ml; P < 0.0005). In the second study, diazoxide (100 mg every 8 h) was administered for 3 d to PCOS subjects (n = 9). Inhibin B increased (85.4 +/- 12.4 to 136.6 +/- 18.8 pg/ml; P < 0.05) in association with a decrease in the insulin area under the curve (104 +/- 29 to 83 +/- 22 nmol/liter.min; P < 0.05) induced by diazoxide. In PCOS subjects, inhibin B demonstrated significant relationships with BMI and factors related to BMI, including LH, insulin, and SHBG. Although LH was associated with inhibin B, hCG administration suppressed inhibin B secretion after 24 h, whereas short-term insulin suppression increased inhibin B. These findings suggest that both increased LH and insulin may account for the relative suppression of inhibin B in patients with PCOS.
抑制素B是生长中的窦前卵泡和窦卵泡颗粒细胞的产物。尽管多囊卵巢综合征（PCOS）女性通常检测到卵巢体积增大和卵泡数量增加，但先前的研究表明，PCOS患者的抑制素B并未如预期那样升高，而是与体重指数（BMI）呈负相关。因此，我们推测PCOS女性的抑制素B水平受与BMI相关的因素调节。于是，对50名无排卵的PCOS受试者进行了检测，在4小时内每隔10分钟采集等量血清样本混合成池，测定其中的促黄体生成素（LH）、性激素和代谢参数，并将其与抑制素B进行相关性分析。基于这些相关性研究结果，直接检测了人绒毛膜促性腺激素（hCG）和胰岛素对抑制素B的调节作用。在PCOS受试者中，抑制素B与BMI（r = -0.413；P < 0.004）和空腹胰岛素（r = -0.409；P < 0.004）呈负相关。抑制素B还与混合池LH（r = 0.419；P < 0.003）、LH脉冲幅度（r = 0.512；P < 0.0001）和性激素结合球蛋白（SHBG）（r = 0.429；P < 0.003）呈正相关。抑制素A未表现出抑制素B所呈现的这些关系，在正常受试者中也不明显。为了确定这些相关性是否代表对抑制素B的调节，即LH对抑制素B的刺激或胰岛素对其的抑制，进行了两项干预性研究。在第一项研究中，对PCOS受试者（n = 15）给予hCG（5000 U）以模拟LH的作用。hCG给药后抑制素B未升高，反而在24小时后显著降低（223.8±21.3 vs. 152.4±15.9 pg/ml；P < 0.0005）。在第二项研究中，对PCOS受试者（n = 9）给予二氮嗪（每8小时100 mg），持续给药3天。二氮嗪诱导胰岛素曲线下面积降低（104±29至83±22 nmol/升·分钟；P < 0.
