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左旋甲状腺素和地塞米松对雄性食蟹猴类固醇动力学的影响。

The effects of l-thyroxine and dexamethasone on steroid dynamics in male cynomologous monkeys.

作者信息

Bourget C, Femino A, Franz C, Hastings S, Longcope C

机构信息

Department of Obstetrics and Gynecology, University of Massachusetts Medical School, Worcester 01605.

出版信息

J Steroid Biochem. 1987 Nov;28(5):575-9. doi: 10.1016/0022-4731(87)90518-8.

Abstract

Male cynomologous monkeys (M. fascicularis) were infused with [3H]androgens, [14C]estrogens and [3H]cortisol before and after the administration of l-thyroxine, (l-T4) 150 micrograms/day for 6 wk, dexamethasone 8 mg every 8 h for 3 doses and dexamethasone 1.0 mg/day for 8 days. Blood samples were obtained before each of the infusions and analyzed for endogenous T, A, E1, E2 and F concentrations, % free T and % free E2, sex hormone-binding globulin (SHBG) and cortisol binding globulin (CBG) capacity. When l-T4 was being administered, T4 and triiodothyronine (T3) concentrations were also measured. Blood samples were obtained during the infusions and analyzed for radioactivity as testosterone (T), androstenedione (A), dihydrotestosterone (DHT), estradiol (E1), estrone (E2), and cortisol (F). All urine was collected for 96 h and an aliquot of the pooled urine was analyzed for radioactivity as estrone and estradiol glucuronide. The administration of l-T4 for 6 wk to 3 monkeys resulted in a marked rise in T4 and T3 levels, from 4.8 +/- 0.4 micrograms/dl and from 136 +/- 6 to 515 +/- 71 ng/dl, respectively. MCRT, MCRE2 and MCRE1 did not change, but MCRA values increased slightly and MCRF increased 2-3 fold. [rho]T.E2 did not change but [rho]A.E1BM showed a slight but significant increase. The inter-conversions between the androgens and between the estrogens were not altered. There was a 2-3-fold increase in SHBG and a decrease in %FT but no change in %FE2 or CBG. The concentrations of T, A and DHT rose but there was no trend in the levels of the estrogens. The administration of dexamethasone 8 mg every 8 h for 3 doses or 1 mg/day for 8 days caused no changes in the MCRs for T, A, E1 and E2 but did cause a significant decrease in MCRF. Measurement of splanchnic and peripheral tissue extractions before and after acute dexamethasone administration in 1 monkey showed that the decrease in MCRF was the result of a marked decrease, 11-2%, in splanchnic extraction of F. The extractions of T and E2 were relatively unaffected. The concentrations of T and F fell but E2 remained the same. % FT and % FE2 rose slightly and the concentrations of SHBG and CBG were unchanged. The androgen interconversions and estrogen interconversions were not affected but [rho]T,E2BM and [rho]A,E1BM showed slight decreases.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

在给雄性食蟹猴(食蟹猴)每日注射150微克左旋甲状腺素(L-T4),持续6周,以及每8小时注射8毫克地塞米松,共注射3剂,随后每日注射1.0毫克地塞米松,持续8天之前和之后,给它们注射[3H]雄激素、[14C]雌激素和[3H]皮质醇。在每次注射前采集血样,分析内源性睾酮(T)、雄烯二酮(A)、雌酮(E1)、雌二醇(E2)和皮质醇(F)浓度、游离T百分比和游离E2百分比、性激素结合球蛋白(SHBG)和皮质醇结合球蛋白(CBG)容量。在注射L-T4期间,还测量了T4和三碘甲状腺原氨酸(T3)浓度。在注射期间采集血样并分析作为睾酮(T)、雄烯二酮(A)、双氢睾酮(DHT)、雌二醇(E1)、雌酮(E2)和皮质醇(F)形式的放射性。收集所有尿液96小时,并对合并尿液的一份等分试样分析作为雌酮和雌二醇葡糖苷酸形式的放射性。给3只猴子注射L-T4 6周导致T4和T3水平显著升高,分别从4.8±0.4微克/分升和136±6升高至515±71纳克/分升。睾酮代谢清除率(MCRT)、雌二醇代谢清除率(MCRE2)和雌酮代谢清除率(MCRE1)未改变,但雄烯二酮代谢清除率(MCRA)值略有增加,皮质醇代谢清除率(MCRF)增加2 - 3倍。睾酮与雌二醇的相关系数(ρT.E2)未改变,但雄烯二酮与雌酮结合球蛋白(ρA.E1BM)略有但显著增加。雄激素之间以及雌激素之间的相互转化未改变。SHBG增加2 - 3倍,游离T百分比降低,但游离E2百分比或CBG无变化。T、A和DHT浓度升高,但雌激素水平无变化趋势。每8小时注射8毫克地塞米松,共注射3剂,或每日注射1毫克地塞米松,持续8天,对T、A、E1和E2的代谢清除率(MCR)无影响,但确实导致MCRF显著降低。对1只猴子急性注射地塞米松前后的内脏和外周组织提取率进行测量表明,MCRF降低是由于内脏对F的提取率显著降低,从11%降至2%。T和E2的提取率相对未受影响。T和F浓度降低,但E2保持不变。游离T百分比和游离E2百分比略有升高,SHBG和CBG浓度未改变。雄激素相互转化和雌激素相互转化未受影响,但ρT,E2BM和ρA,E1BM略有降低。(摘要截断于400字)

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