Elevated steroidogenesis, defective reproductive organs, and XXXX in transgenic male @entity19 overexpressing @entity1 chorionic gonadotropin.

@entity1 @entity249 @entity2785 @entity7807 @entity1465 @entity19 @entity1184 @entity5 @entity342 @entity528
We previously developed a transgenic (TG) @entity19 model that overexpresses the @entity1 chorionic gonadotropin ( @entity1465 ) beta-subunit under the universal @entity1 ubiquitin C promoter, displaying in males a modest 3-fold increase in circulating levels of LH/ @entity1465 bioactivity. The males were fertile and presented with a mild reproductive phenotype. To achieve higher levels of @entity1465 , a double TG model was generated by cross-breeding the @entity7807 -expressing @entity19 with another TG line harboring a ubiquitin C/common alpha-subunit fusion gene. The double-TG @entity19 expressed excessive levels of dimeric @entity1465 , with 2000-fold elevated circulating LH/ @entity1465 bioactivity. These male @entity19 were @entity249 , primarily due to inability to copulate, and they showed enhanced testicular @entity342 production despite clear down-regulation of LH/ @entity1465 receptors. Their intratesticular inhibin B was unaltered, but serum FSH was markedly reduced. Apparently the chronic @entity1465 hyperstimulation led to focal Leydig cell proliferation/ @entity1184 at 6 months of age, but failed to promote @entity5 . Even though full spermatogenesis occurred in most of the seminiferous tubules, progressive @entity528 was apparent as the males grew older. The prostate and seminal vesicles were enlarged by @entity2785 . Functional urethral obstruction was indicated by distension and sperm accumulation in distal vas deferens as well as by dilated urinary bladder and enlarged kidneys. The abnormal function of accessory sex glands and/or lower urinary tract as a consequence of the disturbed sex hormone balance or direct action of @entity1465 may be the main cause of @entity249 in this model. The present study provides in vivo evidence that exposure of male @entity19 to chronically elevated levels of @entity1465 severely affects their urogenital tract function at multiple sites and causes @entity249 , but, unlike in LH/ @entity1465 overexpressing female @entity19 , it is not tumorigenic.
