The pathogenesis of congenital lipoid adrenal hyperplasia in gonads revealed by StAR knockout mice

我使用基因靶向产生类固醇生成急性调节蛋白（星星）敲除小鼠（星星KO）。本研究将星星基因敲除小鼠与自然发生的促性腺激素释放激素（GnRH）基因异常小鼠杂交，获得星星/GnRH双突变小鼠（星星/GnRH doubleKO）。我研究了星星KO和星星/GnRH双KO从出生到8周的性腺组织学。出生时：（1）星星KO中的睾丸在组织间隙中有轻度脂质沉积。卵巢没有。(2)星星/GnRH双基因敲除小鼠睾丸和卵巢均无脂质沉积.从出生到6周：（1）星星KO的睾丸和卵巢都没有大量的脂质沉积。(2)星星/GnRH双基因敲除小鼠睾丸和卵巢均无脂质沉积. 8周：（1）星星/GnRH双基因敲除组睾丸和卵巢发育不良。(2)星星KO的睾丸和卵巢都有大量脂质沉积。(3)星星/GnRH双基因敲除小鼠的睾丸和卵巢均无脂质沉积。(4)外源性促性腺激素处理星星/GnRH双KO可诱导睾丸和卵巢脂质沉积，这些数据有力地表明青春期后星星KO性腺中的脂质沉积是促性腺激素依赖的。

I generated steroidogenic acute regulatory protein (StAR) knockout mice (StAR KO) using gene targeting. I crossed StAR KO mice and naturally occurred gonadotropin-releasiug hormone (GnRH) gene abnormal mice to generate StAR/GnRH double mutant mice (StAR/GnRH double KO). I investigated gonadal histology in StAR KO and StAR/GnRH double KO from birth to 8 weeks.1. at birth : (1) Testes in StAR KO had mild lipid deposits in interstitial space. Ovaries did not. (2) Both testes and ovaries in StAR/GnRH double KO did not have any Iipid deposits.2. from birth to 6 weeks : (1) Both testes and ovaries in StAR KO did not have massive lipid deposits. (2) Both testes and ovaries in StAR/GnRH double KO did not have any lipid deposits.3. 8 weeks : (1) Both testes and ovaries in StAR/GnRH double KO were hypoplastic compared to StAR KO. (2) Both testes and ovaries in StAR KO had massive lipid deposits. (3) Both testes and ovaries in StAR/GnRH double KO lacked lipid deposits. (4) Exogenous gonadotoropin treatment in StAR/GnRH double KO induced lipid deposits in both testes and ovaries.These data strongly indicated that lipid deposits in StAR KO gonads after pubertal age is gonadotoropin dependent.