PCOS患者AMH水平与内分泌代谢异常间关系的研究

目的分析多囊卵巢综合征(PCOS)患者抗苗勒管激素(AMH)水平与内分泌代谢异常之间的关系,比较高雄激素和非高雄激素型患者AMH及其它指标的差异。方法 210例PCOS患者,据AMH水平分为高AMH组(AMH≥10ng/ml,86例)和低AMH组(AMH<10ng/ml,124例);根据高雄激素临床表现或高雄激素血症分为高雄组(58例)和非高雄组(152例)。测定血清AMH、卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇、睾酮(T)、空腹血糖和空腹胰岛素、总胆固醇、甘油三酯和低密度脂蛋白,计算稳态模型胰岛素抵抗指数(HOMA-IR),比较各组AMH及内分泌代谢指标差异,分析AMH水平的影响因素。结果 (1)低AMH组与高AMH组比较,BMI(24.73±5.02kg/m2 vs.23.08±4.34kg/m2)、空腹胰岛素(93.26±57.64pmol/L vs.73.81±42.62pmol/L)、HOMA-IR(3.23±2.20vs.2.51±1.64)均显著增高(P<0.05);(2)高雄组与非高雄组比较,AMH水平(11.71±5.86ng/ml vs.9.64±4.91ng/ml)、LH/FSH比值(1.94±0.93vs.1.54±0.80)、总胆固醇水平(4.94±1.38 mmol/L vs.4.36±0.83 mmol/L)、低密度脂蛋白水平(3.06±1.22 mmol/L vs.2.63±0.68mmol/L)均显著增高(P<0.05);(3)多元线性回归分析显示AMH水平与睾酮水平正相关(β=0.281,P<0.05),与BMI负相关(β=-0.264,P<0.05)。结论 PCOS患者BMI、空腹胰岛素和HOMA-IR升高导致AMH水平降低,而高雄激素型患者AMH水平和LH/FSH显著升高,并增加脂质代谢异常的风险。     

高雄激素通过诱导细胞焦亡影响卵巢颗粒细胞增殖

目的 探讨多囊卵巢综合征(PCOS)中高雄激素对卵巢颗粒细胞焦亡、增殖的影响。方法 3周龄的ICR小鼠随机分为对照组(5只)和PCOS组(5只),PCOS组小鼠连续注射脱氢表雄酮(DHEA,6 mg/100 g体重) 21 d,对照组小鼠则注射等体积不含DHEA的芝麻油。通过HE染色观察两组小鼠卵巢形态的变化；运用实时定量PCR和蛋白免疫印迹(WB)观察炎症及焦亡相关基因和蛋白在小鼠卵巢中的表达情况。通过睾酮(10μmol/L)诱导KGN细胞建立高雄诱导的PCOS体外细胞模型，对照组为不添加睾酮的培养基处理的KGN细胞，PCR法检测对照组和睾酮组细胞中炎症(NLRP3、NF-κB、IL-1β)及焦亡(ASC、Caspase-1)相关基因的表达情况，运用WB和免疫荧光技术观察焦亡相关蛋白(Caspase-1、N-GSDMD/GSDMD)的表达情况，CCK8实验和LDH释放实验观察睾酮对KGN细胞生长的影响。结果 HE染色显示PCOS组小鼠卵巢未成熟小卵泡及闭锁卵泡明显增多，提示PCOS模型构建成功。实时定量PCR结果显示，PCOS小鼠卵巢组织中NLRP3、NF-κB、IL-1β、ASC和...     

CTRP6在小鼠卵巢中的定位、表达以及FSH对CTRP6的调控作用

目的探究C1q/肿瘤坏死因子相关蛋白6(CTRP6)在小鼠卵巢中的定位、表达以及FSH对其调控作用。方法免疫组化对56日龄小鼠卵巢中的CTRP6蛋白进行定位,实时定量PCR检测3 d、10 d、21 d和56 d小鼠、21日龄小鼠注射了孕马血清促性腺激素(PMSG)0 h、12 h、36 h、48 h及注射HCG 4 h、8 h、12 h卵巢中CTRP6 mRNA的表达水平。分别向人卵巢颗粒细胞(KGN)中加入0 ng/ml、1 ng/ml、10 ng/ml和100 ng/ml的FSH和LH,培养24 h后检测CTRP6 mRNA水平。结果小鼠卵巢免疫组化结果显示CTRP6可以在颗粒细胞和卵母细胞中表达,尤其在窦卵泡颗粒细胞中表达水平较高。另外,小鼠CTRP6 mRNA的表达水平随着年龄增加而升高(P0.05),且经PMSG处理不同时长后,CTRP6 mRNA相对表达量较PMSG处理前显著增加(P0.05),而与PMSG处理48 h比较,HCG处理后CTRP6 mRNA的相对表达水平显著降低(P0.05),且随着处理时间的延长呈降低趋势。不同浓度梯度(1、10、100 ng/ml)的FSH处理KGN细胞24 h后均使CTRP6 mRNA表达水平显著增高(P0.05),浓度为10 ng/ml时CTRP6 mRNA水平达峰值。选择10 ng/ml FSH于不同时间梯度(6、12和24 h)处理KGN细胞后,CTRP6 mRNA相对表达量均较未处理前显著增加(P0.05),且随着时间延长呈升高趋势。不同浓度梯度(1、10、100 ng/ml)的LH处理KGN细胞24 h后,CTRP6 mRNA的表达均较LH处理前无显著差异(P0.05)。结论 CTRP6可能参与了卵泡生长发育的调控,是卵泡形成的重要因子。     

多囊卵巢综合征患者血雄激素与胰岛素、黄体生成素水平关系的探讨

血高雄激素是多囊卵巢综合征 (PCOS)的主要生化特征。以往认为高黄体生成素 (LH)是PCOS高雄激素的主要因素 ,现在证明高胰岛素 (INS)与高雄激素关系密切。为了进一步探讨高INS、高LH与高雄激素的关系 ,我们对PCOS患者的血激素水平进行了比较分析。一、材料与方法1 病例选择 :1 998年 3月至 2 0 0 2年 3月在本院妇科内分泌门诊就诊的PCOS患者 1 1 8例 ,入组条件 :(1 )B超监测每侧卵巢有 >1 0个的卵泡直径 2～8mm ,卵巢基质密度增强 ;(2 )月经稀发 ;(3)睾酮 (T)>2 .2nmol/L和 (或 )雄稀二酮 (A) >9nmol/L或黄体生成素 /卵泡刺激…     

在无细胞的猪真皮上培养人角化细胞组成的重组皮肤

由于异体真皮无免疫活性促使开发了在消除潜在抗原性成份的干燥猪皮上培养人角化细胞,并使重组的人/猪皮肤(RHPS)生长成片。 人角化细胞原代培养是用致死量辐照过的3T3细胞作为滋养层。培养基是加有丙酮酸钠(0.12g/l)和NaHCO_3(1g/l)的改良的HMEM,添加10％牛血清、氢考的松0.5μg/ml、胰岛素5μg/1ml、霍乱霉素10~(-10)M、EGF5ng/ml、青霉素200U/ml、链霉素100μg/ml。培养物是在3.5％CO_2湿环境中或密闭的     

芳香化酶抑制剂及其在男科领域的应用

正一、芳香化酶抑制剂芳香化酶(aromatase),即CYP19A,属于细胞色素P450酶类,是体内负责雌激素生物转化的限速酶~([1]),广泛分布于卵巢、睾丸、脂肪组织、乳腺、肝脏和脑,主要作用为催化睾酮和雄烯二醇分别转化为雌二醇(E_2)和雌酮,并可以通过抑制芳香化酶活性来调节雌激素在体内的合成。早在20世纪70年代,就报道了第一批具有芳香化酶抑制作用的化合物~([2])。(一)种类及构效关系按照化合物结构分类,芳香化酶抑制剂(AIs)     

孕期高雄激素法构建多囊卵巢综合征模型大鼠卵巢内胰岛素信号分子的表达

目的 使孕中期雌鼠暴露于高雄激素状态,观察其雌性子代成年后的生殖与代谢状况,构建多囊卵巢综合征（PCOS）大鼠模型.方法 Wistar雌性大鼠,在孕16～18 d颈背部皮下注射丙酸睾丸酮,连续3 d.以其所生雌鼠长至成年作为实验对象,观察其体重及动情周期,并检测血清性激素,17-羟孕酮（17-OHP）、雄烯二酮（A2）及口服葡萄糖耐量试验（OGTT）测血糖、胰岛素水平,评估胰岛素抵抗;运用免疫组化及蛋白印迹方法,检测卵巢组织中胰岛素受体底物（IRS-1、-2）、磷脂酰肌醇3激酶（PI-3K P85）、葡萄糖转运蛋白4（GLUT4）、细胞外信号调节激酶（ERK-1）、17α-羟化酶（CYP17）等蛋白的表达.结果 （1）孕中期雌鼠给予雄激素处理后,其所生雌鼠无明显动情周期,卵巢多囊样改变,睾酮、17-OHP和A2水平明显升高（P〈0.05）;OGTT试验2 h血糖升高（P〈0.05）;葡萄糖曲线下面积增高（P=0.065）;空腹胰岛素水平显著升高（P〈0.05）;OGTT试验0.5 h胰岛素升高（P=0.068）;稳态模型评估（HOMA）指数升高（P〈0.05）.（2）Western blot结果显示模型大鼠卵巢组织IRS-1、IRS-2、PI-3KP85、GLUT4均呈低表达,ERK1、CYP17均呈高表达.结论 给孕中期雌鼠注射丙酸睾丸酮,所生雌鼠表现无排卵、高雄激素血症、胰岛素抵抗、糖耐量低减,符合人类PCOS特征,可以作为PCOS动物模型.卵巢局部胰岛素信号传导蛋白的表达异常.     

脂多糖、TNFα、IL-6、地塞米松和胰岛素对人乳腺癌MCF7细胞GPR54表达的影响

目的:GPR54是下丘脑神经元调控下丘脑-垂体-性腺轴功能的门控,本文研究不同浓度脂多糖(LPS)、肿瘤坏死因子α(TNFα)、白细胞介素6(IL-6)、地塞米松和胰岛素对人乳腺癌MCF7细胞GPR54 mRNA及蛋白表达的影响。方法:培养MCF7细胞,用LPS(10μg/ml和20μg/ml)、TNFα(20 ng/ml和100 ng/ml)、IL-6(10 ng/ml和20 ng/ml)、地塞米松(10-6mol/L和10-7mol/L)和胰岛素(0.01 IU/L和0.1 IU/L)干预72 h,评价干预6、24、48、72 h后GPR54 mRNA(实时荧光定量PCR)和蛋白表达量(Western印迹)的变化。结果:和对照组相比,LPS(10μg/ml和20μg/ml)、TNFα(20 ng/ml和100 ng/ml)、IL-6(10 ng/ml和20 ng/ml)、地塞米松(10-6mol/L和10-7mol/L)和胰岛素(0.01 IU/L和0.1 IU/L)均显著增加GPR54 mRNA(P均0.05)和蛋白表达。结论:LPS、TNFα、IL-6、地塞米松和胰岛素显著增加MCF7细胞GPR54的表达,提示这些炎症因子和激素可能通过调节GPR54水平变化进而影响性腺轴功能。     

EGF和IGF对体外培养兔关节软骨细胞的影响

目的　了解表皮生长因子 (EGF)和胰岛素样生长因子 (IGF)对体外培养兔关节软骨细胞存活数目和分裂增殖百分数的影响。方法　体外培养兔关节软骨细胞传至第 2代 ,分别以EGF、IGF ,以及二者不同的浓度组合作用于软骨细胞。通过酶联免疫检测仪 (MTT)测定软骨细胞存活数 ,流式细胞仪测定软骨细胞分裂增殖百分数。结果　不同浓度EGF对兔关节软骨细胞存活和分裂增殖均有促进作用 ,作用浓度强度次序为 :10ng/ml>0 1ng/ml>10 0ng/ml。不同浓度IGF对兔关节软骨细胞的存活和分裂增殖均有较强促进作用 ,浓度为 5 0ng/ml时 ,刺激效果最显著。EGF与IGF联合使用时 ,刺激效果优于任何一种因子单独使用 ,而以EGF 10ng/ml和IGF 5 0ng/ml为最佳浓度组合。 结论　EGF和IGF都可促进兔关节软骨细胞存活和分裂增殖 ,但以协同作用效果最佳。     

性激素结合球蛋白在多囊卵巢综合征中的研究进展

多囊卵巢综合征(PCOS)是女性常见的内分泌疾病,主要以排卵障碍,卵巢呈多囊样改变和高雄激素血症为特征。性激素结合球蛋白(SHBG)主要作用是结合睾酮和雌激素,调节性激素在血中的浓度。本文对SHBG基因表达水平与PCOS,SHBG水平和胰岛素抵抗(IR)、高雄激素血症、2型糖尿病、代谢综合征(MS)、妊娠糖尿病、乳腺癌和子宫内膜癌等远期并发症的相关性进行综述,以期为PCOS的诊断提供一定参考,为临床治疗提供指导。     

In vivo and in vitro study on 5α-reductase activities in Chinese men

Ｉｎｖｉｖｏａｎｄｉｎｖｉｔｒｏｓｔｕｄｙｏｎ５α－ｒｅｄｕｃｔａｓｅａｃｔｉｖｉｔｉｅｓｉｎＣｈｉｎｅｓｅｍｅｎＺｈａｎｇＧｕｉｙｕａｎ（张桂元），ＣｕｉＹｕｇｕｉ（崔毓桂），ＺｈａｎｇＧｕａｎｇｈｕａ（张光华）ＺｈａｎｇＺｈｉｊｕａｎ（张芝娟），...     

男性胎儿5α-还原酶活性和雄激素及其受体的研究

目的 :分析男性胎儿雄激素靶组织外生殖器皮肤的雄激素 (T、DHT)水平、5α 还原酶活性及雄激素受体(AR)配基结合能力 ,探讨其在性别分化成熟中的作用。　方法 :4例孕 16～ 2 0周因意外事件而被迫引产的胎儿 ,取其包皮和阴茎皮肤组织。 10例 4～ 7岁和 2 3例 2 0～ 3 4岁男性因包茎或包皮过长行包皮环切术后的组织 ,制备匀浆 ,经差速超速离心 ,分别制备胞质、核浆和微粒体 3种组份 ,RIA方法测定匀浆中T、DHT水平 ,按作者建立和改良的方法分析 5α 还原酶活性及雄激素受体 (AR)配基结合能力 (B)。　结果 :孕 16～ 2 0周男性胎儿靶组织T为 ( 4 .5 5± 2 .84 )pmol/(mg蛋白·ml) ,DHT为 ( 3 9.12± 17.3 0 )pmol/(mg蛋白·ml) ;5α 还原酶 Ⅰ 型同工酶活性为 ( 162 .15±3 6.94 )pmol/(mg蛋白·3 0min) ,Ⅱ 型同工酶活性为 ( 3 0 7.62± 4 0 .5 5 )pmol/(mg蛋白·3 0min) ;胞质AR的B值为 ( 18.86± 7.62 )fmol/mg蛋白 ,核内AR的B值为 ( 10 8.5 5± 4 9.3 4 )fmol/mg蛋白。各项参数均高于儿童时期 ;除AR外 ,甚至高于成年男子 (P <0 .0 5～ 0 .0 1)。　结论 :胎儿时期雄激素靶组织中具有高水平的雄激素及其受体 ,尤其DHT ,提示雄激素在介导男性外生殖器分化形成和成熟中起重要的调控作用。     

The Benefits of Dual Inhibition of 5α Reductase

In humans, androgens balance cell proliferation and apoptosis, ensuring normal growth and development of the prostate, but also driving pathologic gland enlargement in benign prostatic hyperplasia (BPH) and prostate cancer. The two main androgens are testosterone and dihydrotestosterone (DHT). Reducing testosterone levels results in significant sexual side-effects, whereas reducing DHT does not result in any major safety or tolerability issues. DHT is synthesised from testosterone by the 5α-reductase enzyme, of which there are two isozymes, type I and type II. Expression of both of these isozymes is increased in BPH. Two 5α-reductase inhibitors (5ARIs) are available for BPH management; the dual inhibitor dutasteride inhibits type I and type II 5α reductase, whereas finasteride inhibits only the type II isoenzyme. Pharmacologic studies indicate that the dual 5ARI dutasteride results in greater suppression of DHT than the type II inhibitor. A phase 2, double-blind, placebo-controlled study conducted in men with BPH demonstrated that maximal DHT suppression is achieved in a larger proportion of patients with dutasteride than with finasteride. Dutasteride demonstrates sustained improvement in symptom score and maximal flow rate with no increase in prostate volume up to 4 yr.     

Comparison of finasteride (proscar®), a 5α reductase inhibitor,and various commercial plant extracts in in vitro and in vivo 5α reductase inhibition

Human prostate was used as a source of 5α reductase. Compounds were incubated with an enzyme preparation and [³H]testosterone. [³H]-dihydrotestosterone production was measured to calculate 5ã reductase activity. IC₅₀ values (ng/ml) were finasteride = 1; Permixon = 5,600; Talso = 7,000; Strogen Forte = 31,000; Prostagutt = 40,000; and Tadenan = 63,000. Bazoton and Harzol had no activity at concentrations up to 500,000 ng/ml. In castrate rats stimulated with testosterone (T) or dihydrotestosterone (DHT), finasteride, but not Permixon or Bazoton, inhibited T stimulated prostate growth, while none of the three compounds inhibited DHT stimulated growth. These results demonstrate that finasteride inhibits 5α reductase, while Permixon and Bazoton have neither anti-androgen nor 5α reductase inhibitory activity. In addition, in a 7 day human clinical trial, finasteride, but not Permixon or placebo, decreased serum DHT in men, further confirming the lack of 5α reductase inhibition by Permixon. Finasteride and the plant extracts listed above do not inhibit the binding of DHT to the rat prostatic androgen receptor (concentrations to 100 μg/ml). Based on these results, it is unlikely that these plant extracts would shrink the prostate by inhibiting androgen action or 5α reductase. © 1993 Wiley-Liss, Inc.     

Comparison of the effects of new specific azasteroid inhibitors of steroid 5α-reductase on canine hyperplastic prostate: Suppression of prostatic DHT correlated with prostate regression

Four new azasteroid inhibitors of steroid 5α-reductase were compared to the benchmark compound finasteride, each at a dose level of 1 mg/kg/day, as well to placebo and to castration, in seven groups of mature male beagle dogs with enlarged prostates. Prostate volumes were measured repetitively by a volume MRI method over 15 weeks of treatment. The study probed the obverse of the familiar relation between DHT and prostate growth, and provides the first documentation of a tight negative correlation between prostate regression and the prostatic concentration of DHT across a range of treatment regimens (r = ?0.982). In this first direct comparison study of structure vs. in vivo activity for several azasteroids in the dog model of BPH, relative efficacy for induction of shrinkage of the dog prostate did not correlate at all with the inhibitor's relative activity against the dog 5α-reductase in vitro. On the basis of the relative IC₅₀ values it would not have been predicted that, at the dose tested, the analogue MK-434 (17β-benzoyl-4-aza-5α-androst-1-en-3-one) was distinguished from the other inhibitors with respect to the induction of faster and more complete regression (69%) as well as greater reduction in prostatic DHT (95%), both of which approached the castrated dog levels of 75% prostatic shrinkage and >98% reduction in DHT. Treatment with any one of the five azasteroids induced two- to five-fold increases in prostatic testosterone. However, total androgen was conserved at the placebo control level. Despite the differences noted, each azasteroid tested induced a highly significant decrease in prostatic volume that correlated tightly with a decreased prostatic DHT level in canine spontaneous BPH.     

LY207320 (6-methylene-4-pregnene-3,20-dione) inhibits testosterone biosynthesis,androgen uptake, 5α-reductase,and produces prostatic regression in male rats

LY207320 is an in vitro inhibitor (estimated IC₅₀ = 0.06 μM) of steroid 5α-reductase that catalyzes the conversion of testosterone (T) to dihydrotestosterone (DHT). In contrast, LY207320 was only moderately active against rat prostatic 5α-reductase in vivo (32% inhibition at 50.0 mg/kg single dose). LY207320 did, however, inhibit the in vivo uptake of [³H]-T by the prostate. The antiprostatic and endocrine effects of this agent were evaluated following daily (21 days) administration to castrated, androgen-supplemented castrate, and intact rats. LY207320, which has modest progestational competitive binding activity, does not bind to rat prostatic androgen or uterine estrogen cytosolic receptors. In the castrated male rat, subcutaneously (s.c.) administered LY207320 had no androgen agonist activity, as evidenced by a lack of accessory sex organ weight gains. Administration of s.c. LY207320 to intact rats for 21 days at doses greater than 5.0 mg/kg-day produced significant (P <0.05) reductions of seminal vesicle and ventral prostatic weights (maximal regression = ?65% and ?40% from control values, respectively at 50.0 mg/kg-day). The compound had no regressive activity on male accessory sex organs when administered orally. LY207320 did not alter circulating prolactin, LH, or corticosterone levels, but at high doses (>m50.0 mg/kg-day), lowered circulating T[?67% from intact control levels (P <0.05)]. Histological analysis of the rat ventral prostates (RVPs) in LY207320-treated rats was consistent with an androgen-deprived state. Decreased circulating androgens and prostatic regression are associated with inhibition of testicular 17α-hydroxy/C17,20-lyase enzyme activity (IC⁵⁰ = 0.06 μM). These findings support the contention that LY207320 is a physiological antagonist of androgen action in male rats, and that its effects are mediated primarily through inhibition of testicular androgen production rather than accessory sex organ 5α-reductase. © 1993 Wilcy-Liss, Inc.     

Clinical and endocrinological studies of the luteinizing hormone-releasing hormone analogue therapy in prostatic cancer patients

A luteinizing hormone-releasing hormone (LH-RH) analogue was administered for 3 to 32 months to 15 prostatic cancer patients in stage B-D (B:3, C:8, D:4). Intratesticular, intratubular and prostatic androgen levels were measured by radioimmunoassay before and after LH-RH analogue therapy. The measurement of serum prostatic acid phosphatase (PAP) and prostatic specific antigen (PA) levels was also conducted. Thereafter, we assessed the effect of the LH-RH analogue on androgen levels and the relation of prostatic tissue 5 alpha-dihydrotestosterone (DHT) level to the clinical response. The results were as follows: 1) Johnsen's mean germinal epithelium count was significantly decreased from 7.7 +/- 2.1 (mean +/- S.D.) to 4.3 +/- 2.3, and the wall thickness of seminiferous tubules was increased from 5.93 +/- 1.31 to 11.9 +/- 3.64 microns. 2) Plasma testosterone (T), intratesticular and intratubular androgen levels were significantly decreased (plasma T: from 4.40 +/- 1.84 to 0.61 +/- 0.32 ng/ml, intratesticular T: from 335.3 +/- 170.3 to 4.6 +/- 3.8 ng/g.t.w., DHT: from 25.3 +/- 11.7 to 3.7 +/- 2.7 ng/g.t.w., intratubular T: from 50.8 +/- 36.6 to 0.10 +/- 0.99 ng/g.t.w. and DHT: 7.54 +/- 3.20 to 0.63 +/- 0.90 ng/g.t.w.). 3) Crude nuclear DHT levels in prostatic tissue fell from 15.3 +/- 9.3 (N = 8) to 0.37 +/- 0.54 pg/mg protein (N = 3) and the level was non-detectable in 5 of 8 cases. 4) Complete remission was achieved in 1 patient, partial response in 5, objective stable in 8, and objective progression in 1 patient, according to Shimazaki's criteria.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma levels of dihydrotestosterone remain in the normal range in men treated with long-acting parenteral testosterone undecanoate

The major goal of androgen therapy is to achieve testosterone levels as close to physiological concentrations as possible. For some androgen-dependent functions, testosterone is a pro-hormone, peripherally converted to 5 alpha-dihydrotestosterone (DHT) and 17beta-oestradiol of which the levels preferably should also be within their normal physiological ranges. In this study, the resulting plasma DHT levels in 122 hypogonadal men treated with a novel testosterone treatment modality: parenteral long-acting testosterone undecanoate (Nebido), were investigated. Following the treatment, there were no abnormally high/low plasma DHT levels; levels varied between 86 and 511 ng l(-1) (normal range: 40-575 ng l(-1)). In conclusion, treatment with testosterone undecanoate generates physiological levels of DHT. Prostate safety parameters did not undergo changes.     

A prospective analysis of the time to normalization of serum androgens following 6 months of androgen deprivation therapy in patients on a randomized phase III clinical trial using limited hormonal therapy

PURPOSE: Patients with prostate cancer are treated with neoadjuvant, adjuvant and intermittent therapy with gonadotropin-releasing hormone agonists (GnRH-A). While these are largely successful in decreasing testosterone (T) and dihydroxytestosterone (DHT) to castrate levels, discontinuation of such therapy often results in continued suppression of androgens for variable periods of time. We present the largest published series of patients evaluating the timing of T and DHT increase after cessation of GnRH therapy. MATERIALS AND METHODS: Serial T and DHT measurements were prospectively obtained every 3 months while on GnRH-A then monthly upon discontinuation of GnRH-A. Analysis of time from the second 3-month GnRH-A administration to T and DHT increase was undertaken. RESULTS: A total of 80 evaluable patients had a median time to T 50 ng/dl or greater of 12.9 weeks and a median time to T normalization (212 ng/dl or greater) of 16.6 weeks. Low baseline T was associated with a prolonged time to T 212 ng/dl or greater (p = 0.0086) and a similar trend was seen in patients older than 66 years (p = 0.08). There were 62 evaluable patients with a median of 14.9 weeks to DHT 150 pg/ml or greater. There was no association with Gleason score at diagnosis, on study prostate specific antigen, type of prior definitive therapy, or any prior hormonal therapy and time to increase in circulating androgens. CONCLUSIONS: After 6 months of GnRH-A therapy in these patients, DHT and T levels did not return to normal for a median of 14.9 and 16.6 weeks, respectively.     

Hormonal Milieu of the Seminiferous Tubules in the Normal and Cryptorchid Rat

The intratesticular concentration of androgens seems to be of more importance for normal spermatogenesis than the concentration of androgens in the peripheral blood.
Therefore, the levels of testosterone, 5α - dihydrotestosterone (DHT), androstenedione and FSH in the interstitial fluid of the rat testis were determined by radioimmunoassay. The following concentrations were obtained from the interstitial fluid of normal rats and from rats cryptorchid between 60 and 90 days of age: Testosterone 137 ± 25 (mean ± SEM) and 271 ± 34 ng/ml, DHT 11 ± 2 and 22 ± 5 ng/ml, androstenedione 8 ± 2 and 20 ± 4 ng/ml, respectively. The sum of testosterone and DHT in serum did not differ in the two groups. Serum FSH concentrations were significantly increased in the cryptorchid rats (942 ± 73 ng/ml) as compared to the control rats (600 ± 38 ng/ml). These elevated levels were also found in the testicular interstitial fluid (425 ± 33 ng/ml in controls, 641 ± 43 ng/ml in cryptorchid rats). It is thus evident that in the cryptorchid rat, both FSH and androgens are available to the seminiferouse tubules in significantly elevated amounts. Since these are the only hormones which are known to be of importance in spermatogenesis, the impaired Sertoli cell function and depletion of germinal cells in cryptorchidism is not due to an absolute shortage of stimulatory hormones.