PERIPHERAL ANDROGEN ACTION IN HIRSUTISM

有人建议，血清3-α-雄烷二醇(3)的测定 α-二醇)反映外周雄激素的产生。最近，我们 已证明血清3-α-二醇葡萄糖醛酸苷(3-α-二醇G)来源于 几乎完全来自内脏外来源，是一个更好的标志 PAP是未共轭的3α-二醇。在患有特发性多毛症的女性中， 我们发现，几乎所有女性的3α-二醇G水平都升高 尽管其他雄激素水平正常。在多囊卵巢综合征患者中 卵巢综合征(PCO)，我们已经表明，虽然所有女性都表现出 来自腺体来源的雄激素水平，是否存在 多毛症可以用PAP来解释，如血清测量所反映的 3Alpha-diol G。然而，3Alpha-diol G的血源尚未 已经建立了。目前尚不清楚血液中DHT和3的水平 α-二醇G是平衡的，或者如果它们存在于不同的池中。3. α-二醇G部分通过5α还原酶(5αR)和 可能反映了5αR在外周组织中的活性。因此，我们 将尝试将血清3α二醇G与体外5αR联系起来 女性的活动。螺内酯(S)是一种受体阻滞剂。 改善多囊卵巢的多毛症。S治疗是否改变血清3-α-二醇-G 如果这与多毛症的改善有关，应该是 调查过了。在项目1中，我们建议获取血液和生殖器皮肤 来自15名排卵的绝经前患者，来自15名患有多毛症的妇女 PCO和15名正常男性。我们将尝试将测量结果与 血清DHT、3Alpha-diol G与体外DHT和3Alpha-diol产生。 在项目2中，将静脉输注~3H-DHEA、~H-Adione和~H-DHT 进入10名H-PCO妇女和6名对照组，直到达到稳定状态。转换 这些前体类固醇和3α-二醇G之间的比例将为 计算出来的。此外，为期2天的地塞米松抑制试验和 将进行6小时的ACTH输注，以帮助确定 血清3α二醇G的来源在项目3中，30名H-PCO妇女将是 S治疗多毛症及激素的临床评价 治疗前后每隔3个月进行一次测量 已经18个月了。将记录毛干直径和生殖器皮肤 10名患者在治疗后将获得活检。这些研究 将有助于确定PAP的流行率和5Alpha R活动增加 3-α-二醇-G及其相关指标在后发性白内障中的临床应用 血源(S)。S治疗H-PCO的临床疗效观察 妇女将与PAP的任何变化的评估进行比较 3α二醇和5αR活性的测定反映了这一现象。

It has been suggested that measurements of serum 3 Alpha-androstanediol (3 Alpha-diol) reflect peripheral androgen production (PAP). Recently, we have shown that serum 3 Alpha-diol glucuronide (3 ALpha-diol G) is derived almost exclusively from extrasplanchnic sources and is a better marker of PAP than is unconjugated 3 Alpha-diol. In women with idiopathic hirsutism, we found that virtually all women had elevated levels of 3 Alpha-diol G despite normal levels of other androgens. In patients with polycystic ovary syndrome (PCO), we have shown that while all women exhibit elevated levels of androgens derived from glandular sources, the presence or absence of hirsutism may be explained by PAP as reflected by measurements of serum 3 Alpha-diol G. Nevertheless, the blood source of 3 Alpha-diol G has not been established. It is not known whether blood levels of DHT and 3 Alpha-diol G are in equilibrium or if they exist in separate pools. 3 Alpha-diol G is produced, in part, via 5 Alpha reductase (5 Alpha R) and probably reflect 5 Alpha R activity in peripheral tissues. Therefore, we will attempt to correlate serum 3 Alpha-diol G with in vitro 5 Alpha R activity in women. Spironolactone (S) is a receptor blocking agent which improves hirsutism in PCO. Whether S therapy changes serum 3 Alpha-diol G and if this correlates with the improvement in hirsutism should be investigated. In project #1 we propose to obtain blood and genital skin from 15 ovulatory premenopausal patients, from 15 hirsute (H) women with PCO and from 15 normal men. We will attempt to correlate measurements of serum DHT, 3 Alpha-diol G with in vitro DHT and 3 Alpha-diol production. In project #2, 3H-DHEA, 3H-Adione and 3H-DHT will be infused intravenously into 10 H-PCO women and 6 controls until steady state occurs. Conversion ratios between these precursor steroids and 3 alpha-diol G will be calculated. In addition, a 2-day dexamethasone suppression test and a 6-hour ACTH infusion will be carried out in order to help determine the source of serum 3 Alpha-diol G. In project #3, 30 H-PCO women will be treated with S and have the clinical assessment of hirsutism and hormonal measurements carried out before and after treatment at 3-month intervals for 18 months. Hair shaft diameters will be recorded and genital skin biopsies will be obtained after treatment in 10 patients. These studies will help establish the prevalence of PAP and increased 5 Alpha R activity in PCO, the clinical usefulness of measurements of 3 Alpha-diol G and its source(s) in blood. The clinical benefits of treatment with S in H-PCO women will be compared with the assessment of any changes in PAP as reflected by measuremets of 3 Alpha-diol and in 5 Alpha R activity.