Prenatal hyperandrogenization induces metabolic and endocrine alterations which depend on the levels of testosterone exposure.
Prenatal hyperandrogenization induces metabolic and endocrine alterations which depend on the levels of testosterone exposure.
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DOI：
10.1371/journal.pone.0037658
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Motta AB
中科院分区：
文献类型：
--
作者：
Amalfi S;Velez LM;Heber MF;Vighi S;Ferreira SR;Orozco AV;Pignataro O;Motta AB
产前高雄激素血症可诱发大鼠多囊卵巢综合征（PCOS）。本研究的目的是确定产前睾酮水平是否可以决定成年期间代谢和内分泌变化的程度。从妊娠第16天至第19天，妊娠Sprague道利大鼠产前注射2或5 mg游离睾酮（分别为T2和T5组）。T2和T5的雌性后代在成年期表现出不同的PCOS表型。T2的后代表现为高雄激素血症、卵巢囊肿和排卵周期，而T5的后代表现为高雄激素血症、卵巢囊肿和无排卵周期。两组在腹膜内葡萄糖耐量试验（IPGTT;胰岛素抵抗评估）后均显示循环葡萄糖水平升高。IPGTT在T5大鼠中较高，并且与青春期前年龄的体重直接相关。然而，在青春期前的体重下降在成年生活中得到补偿。虽然两组都显示卵巢类固醇生成增强，但似乎涉及的分子机制不同。较高剂量的睾酮增强了调节胆固醇可用性的蛋白质（类固醇生成急性调节蛋白（星星））和转录因子过氧化物酶体增殖物激活受体γ（PPAR γ）的蛋白质表达。产前高雄激素诱导的抗氧化反应，防止可能的促氧化状态。较高剂量的睾酮通过增加前列腺素E（PG）水平和环氧合酶2（COX 2，PGs合成的限制酶）的蛋白表达诱导卵巢组织中的促炎状态。总之，我们的数据表明，产前注射的睾酮水平调节子宫环境，这反过来又会导致成年期内分泌和代谢异常以及PCOS的表型。
Prenatal hyperandrogenism is able to induce polycystic ovary syndrome (PCOS) in rats. The aim of the present study was to establish if the levels of prenatal testosterone may determine the extent of metabolic and endocrine alterations during the adult life. Pregnant Sprague Dawley rats were prenatally injected with either 2 or 5 mg free testosterone (groups T2 and T5 respectively) from day 16 to day 19 day of gestation. Female offspring from T2 and T5 displayed different phenotype of PCOS during adult life. Offspring from T2 showed hyperandrogenism, ovarian cysts and ovulatory cycles whereas those from T5 displayed hyperandrogenism, ovarian cysts and anovulatory cycles. Both group showed increased circulating glucose levels after the intraperitoneal glucose tolerance test (IPGTT; an evaluation of insulin resistance). IPGTT was higher in T5 rats and directly correlated with body weight at prepubertal age. However, the decrease in the body weight at prepubertal age was compensated during adult life. Although both groups showed enhanced ovarian steroidogenesis, it appears that the molecular mechanisms involved were different. The higher dose of testosterone enhanced the expression of both the protein that regulates cholesterol availability (the steroidogenic acute regulatory protein (StAR)) and the protein expression of the transcriptional factor: peroxisome proliferator-activated receptor gamma (PPAR gamma). Prenatal hyperandrogenization induced an anti-oxidant response that prevented a possible pro-oxidant status. The higher dose of testosterone induced a pro-inflammatory state in ovarian tissue mediated by increased levels of prostaglandin E (PG) and the protein expression of cyclooxygenase 2 (COX2, the limiting enzyme of PGs synthesis). In summary, our data show that the levels of testosterone prenatally injected modulate the uterine environment and that this, in turn, would be responsible for the endocrine and metabolic abnormalities and the phenotype of PCOS during the adult life.
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DOI：
10.1590/s0100-879x2000001100012
发表时间：
2000-11-01
影响因子：
2.3
作者：
González, E;Roselló-Catafau, J;Gimeno, M
通讯作者：
Gimeno, M
影响因子：
3.6
作者：
Froment, P;Fabre, S;Monget, P
通讯作者：
Monget, P
影响因子：
4.8
作者：
Birch, RA;Padmanabhan, V;Robinson, JE
通讯作者：
Robinson, JE
影响因子：
4.8
作者：
Cui, Y;Miyoshi, K;Hennighausen, L
通讯作者：
Hennighausen, L
DOI：
10.1002/dvg.1020170402
发表时间：
1995-01-01
期刊：
DEVELOPMENTAL GENETICS
影响因子：
--
作者：
Crawford, MJ;Liversage, RA;Varmuza, SL
通讯作者：
Varmuza, SL