PERIPHERAL ANDROGEN ACTION IN HIRSUTISM

有人建议，血清3 α-雄甾烷（3 α-二醇）反映外周雄激素产生（PAP）。 最近我们 已经证明血清3 α-二醇葡萄糖醛酸苷（3 α-二醇G） 几乎完全来自外planchnic来源，是一个更好的标记， PAP比非共轭的3 α-二醇更好。 在患有特发性多毛症的女性中， 我们发现几乎所有的女性体内的3 α-二醇G 尽管其他雄激素水平正常 多囊 卵巢综合征（PCO），我们已经表明，虽然所有的妇女表现出升高， 来自腺体来源的雄激素水平，是否存在 多毛症的原因可能是PAP，如血清 3 α-二醇G. 然而，3 α-二醇G的血液来源没有 确立了习 目前尚不清楚血液中的DHT和3 α-二醇G处于平衡状态，或者它们存在于单独的库中。 3 α-二醇G部分地通过5 α还原酶（5 α R）产生， 可能反映了外周组织中的5 α R活性。 所以我们 将尝试将血清3 α-二醇G与体外5 α R 在女性中的活动。 螺内酯（S）是一种受体阻断剂， 改善PCO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， 研究了 在项目#1中，我们建议获得血液和生殖器皮肤 从15名排卵的绝经前患者，从15名多毛（H）妇女， PCO和15名正常男性。 我们将尝试关联测量 血清DHT、3 α-二醇G与体外DHT和3 α-二醇产生。 在项目#2中，将静脉输注3 H-DHEA、3 H-Adione和3 H-DHT 10名H-PCO女性和6名对照，直至达到稳态。 转换 这些前体类固醇和3 α-二醇G之间的比例将是 计算了 此外，2天地塞米松抑制试验和 6-将进行10小时ACTH输注，以帮助确定 血清3 α-二醇G来源。 在项目3中，将有30名H-PCO妇女 用S治疗，并进行多毛症和激素的临床评估 治疗前后每隔3个月进行一次测量 18个月 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组织检查。 这些研究 将有助于确定PAP的患病率和5 α R活性的增加 在PCO中，测量3 α-二醇G及其 血的来源。 S治疗H-PCO的临床获益 妇女将与PAP的任何变化评估进行比较， 通过测量3 α-二醇和5 α R活性反映。

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.