Transgenic and knockout mouse models for aberrant pituitary-testicular function: relevance to the pathogenesis of cryptorchidism.

Abstract

In recent years novel information about the hormonal regulation of testicular descent has emerged from genetically modified mice and other experimental animal models with cryptorchid phenotypes. We have studied transgenic (TG) mice overexpressing P450 aromatase (AROM+) and insulin-like 3 (INSL3+), and knockout (KO) mice for the genes of LH receptor (R) (LuRKO) and the thyroid-specific enhancer/binding protein T/ebp/Nkx2.1. LuRKO and AROM+ males are cryptorchid, while the INSL3 overexpressing females present with transabdominal descent of the ovaries. The T/ebp/Nkx2.1 KO mice die at birth, but the transabdominal phase of their testicular descent is normal despite the lack of pituitary gland. Detailed analysis of these mouse models brings novel information about the hormonal requirements, and their spatio-temporal aspects, in testicular descent, and how this process is affected by too low or too high hormone levels, or by imbalance in concentrations of critically important hormones.