Hedström Helena, Bäckström Torbjörn, Bixo Marie, Nyberg Sigrid, Wang Mingde, Gideonsson Ida, Turkmen Sahruh
Department of Clinical Science, Obstetrics and Gynecology, Umeå Neurosteroid Research Center, Umeå University, Umeå, Sweden.
Clin Endocrinol (Oxf). 2015 Nov;83(5):643-50. doi: 10.1111/cen.12809. Epub 2015 May 25.
Several studies have reported that γ-aminobutyric acid (GABA) ergic circuits are involved in the pathophysiology of polycystic ovary syndrome (PCOS). The progesterone metabolite allopregnanolone is a potent GABA(A) -receptor-modulating steroid, and patients may have increased concentrations of allopregnanolone or altered GABAA receptor sensitivity. We investigated both of these possibilities in this study.
We enrolled 9 women with PCOS and 24 age-matched eumenorrhoeic controls, who were divided into two groups by body mass index (BMI) (16 normal weight and 8 overweight).
We investigated the effects of allopregnanolone injection on GABA(A) receptor sensitivity in both groups of women. All women received a single intravenous dose of allopregnanolone (0·050 mg/kg). GABA(A) receptor sensitivity was assessed with the saccadic eye velocity (SEV) over 30° (SEV30°), the SEV30°/allopregnanolone concentration ([Allo]) ratio, and sedation, which were measured together with serum allopregnanolone at intervals for 180 min after injection. The controls were tested in the follicular phase of the menstrual cycle.
Baseline allopregnanolone concentrations were higher in the PCOS women than in the normal-weight (P = 0·034) and overweight controls (P = 0·004). The allopregnanolone concentrations after injection were higher in the PCOS women (P = 0·006) and overweight controls (P = 0·037) than in the normal-weight controls. All groups showed a decline in the SEV30°/[Allo] ratio after injection. Allopregnanolone had a smaller effect on the SEV30°/[Allo] ratio in the overweight women (PCOS, P = 0·032; controls, P = 0·007) than in the normal-weight controls. The sedation score after allopregnanolone injection was lower in the PCOS patients than in the controls, but was not different between the two control groups.
PCOS women had elevated baseline allopregnanolone concentrations compared with follicular-phase controls. All overweight women (PCOS and controls) were less sensitive to allopregnanolone than normal-weight controls.
多项研究报告称，γ-氨基丁酸（GABA）能神经回路参与多囊卵巢综合征（PCOS）的病理生理过程。孕酮代谢产物别孕烯醇酮是一种强效的GABA（A）受体调节类固醇，PCOS患者体内别孕烯醇酮浓度可能升高，或GABAA受体敏感性发生改变。在本研究中，我们对这两种可能性均进行了调查。
我们招募了9例PCOS女性患者和24例年龄匹配的月经正常的对照者，后者根据体重指数（BMI）分为两组（16例体重正常者和8例超重者）。
我们调查了别孕烯醇酮注射对两组女性GABA（A）受体敏感性的影响。所有女性均接受单次静脉注射别孕烯醇酮（0.050 mg/kg）。通过30°眼跳速度（SEV）、SEV30°/别孕烯醇酮浓度（[Allo]）比值以及镇静程度来评估GABA（A）受体敏感性，并在注射后180分钟内每隔一段时间与血清别孕烯醇酮一起进行测量。对照组在月经周期的卵泡期进行测试。
PCOS女性的基线别孕烯醇酮浓度高于体重正常的对照组（P = 0.034）和超重对照组（P = 0.004）。注射后，PCOS女性（P = 0.006）和超重对照组（P = 0.037）的别孕烯醇酮浓度高于体重正常的对照组。所有组在注射后SEV30°/[Allo]比值均下降。与体重正常的对照组相比，别孕烯醇酮对超重女性（PCOS组，P = 0.032；对照组，P = 0.007）的SEV30°/[Allo]比值影响较小。PCOS患者注射别孕烯醇酮后的镇静评分低于对照组，但两个对照组之间无差异。
与卵泡期对照组相比，PCOS女性的基线别孕烯醇酮浓度升高。所有超重女性（PCOS组和对照组）对别孕烯醇酮的敏感性均低于体重正常的对照组。
