Han X F, Cheng W, Chen Z Y, Du X G, Cao X H, Zeng X Y
Isotope Research Lab, Sichuan Agricultural University, Ya'an, People's Republic of China.
Isotope Research Lab, Sichuan Agricultural University, Ya'an, People's Republic of China.
Domest Anim Endocrinol. 2014 Jul;48:126-35. doi: 10.1016/j.domaniend.2014.04.001. Epub 2014 Apr 12.
To investigate the effects of antitestosterone immunization, initiated during early puberty, on hypothalamic-pituitary-testicular feedback in rabbits, 16 early pubertal male rabbits were randomly allocated into 2 groups (n = 8), control or immunized against testosterone-3(O-carboxymethyl)oxime-BSA in Freund adjuvant at 4 mo of age (with a booster immunization 4 wk later). Blood samples (for antibody titers and hormone concentrations) were collected at 2- or 4-wk intervals after immunization. Compared with controls, antitestosterone immunization triggered: a substantial and sustained antibody response (P < 0.01); increases in serum concentrations of luteinizing hormone (LH) and testosterone and testis weight and volume (P < 0.05); hyperplasia of testicular interstitial tissue with clustered and hypertrophic Leydig cells; and greater (P < 0.05) enzyme protein and messenger RNA (mRNA) expression levels for testicular cholesterol side-chain cleavage cytochrome P-450, 17α-hydroxylase cytochrome P-450, and 3β-dydroxysteroid dehydrogenase. Furthermore, immunoneutralization of testosterone upregulated mRNA expressions for genes in sex steroid negative feedback loops, including androgen receptor (AR), estrogen receptor alpha (ER-α), kisspeptin encoded gene (kiss-1) and kisspeptin receptor (G-coupled receptor 54) and gonadotropin-releasing hormone (GnRH) in the hypothalamic arcuate nucleus, GnRH receptor and LH-β in pituitary, and AR, inhibin-α and βA subunits in testes (P < 0.05). However, immunization did not affect mRNA expressions for follicle-stimulating hormone β, AR, and ER-α in pituitary, or ER-α in testes. We concluded that antitestosterone immunization in male rabbits, initiated during early puberty, increased GnRH mRNA expression, and in turn LH synthesis by reducing testicular feedback signaling. Reduction of direct steroidal effects on the testis may also have increased testosterone secretion. Consequently, there was an accelerated testicular development during puberty and enhanced testicular function after puberty, which likely conferred prolonged reproductive advantages.
为研究青春期早期开始的抗睾酮免疫对兔下丘脑 - 垂体 - 睾丸反馈的影响，将16只青春期早期雄性兔随机分为2组（n = 8），一组为对照组，另一组在4月龄时用睾酮 - 3（O - 羧甲基）肟 - 牛血清白蛋白与弗氏佐剂进行免疫（4周后进行加强免疫）。免疫后每隔2周或4周采集血样（用于检测抗体效价和激素浓度）。与对照组相比，抗睾酮免疫引发了：强烈且持续的抗体反应（P < 0.01）；黄体生成素（LH）和睾酮的血清浓度增加，睾丸重量和体积增加（P < 0.05）；睾丸间质组织增生，伴有成群且肥大的莱迪希细胞；以及睾丸胆固醇侧链裂解细胞色素P - 450、17α - 羟化酶细胞色素P - 450和3β - 羟类固醇脱氢酶的酶蛋白和信使核糖核酸（mRNA）表达水平更高（P < 0.05）。此外，睾酮的免疫中和上调了性类固醇负反馈回路中基因的mRNA表达，包括下丘脑弓状核中的雄激素受体（AR）、雌激素受体α（ER - α）、亲吻素编码基因（kiss - 1）和亲吻素受体（G蛋白偶联受体54）以及促性腺激素释放激素（GnRH），垂体中的GnRH受体和LH - β，以及睾丸中的AR、抑制素α和βA亚基（P < 0.05）。然而，免疫并未影响垂体中促卵泡激素β、AR和ER - α的mRNA表达，或睾丸中ER - α的mRNA表达。我们得出结论，青春期早期开始的雄性兔抗睾酮免疫通过减少睾丸反馈信号增加了GnRH mRNA表达，进而增加了LH合成。对睾丸直接甾体作用的减少也可能增加了睾酮分泌。因此，青春期期间睾丸发育加速，青春期后睾丸功能增强，这可能带来延长的生殖优势。
