Molecular characterization of postnatal development of testicular steroidogenesis in luteinizing hormone receptor knockout mice.

We recently demonstrated that the sexual development of LH receptor (LHR) knockout mice is normal until birth, but is totally arrested thereafter. To study further the functional defects of LHR knockout mice, the expression of selected Leydig cell-specific genes was studied in (-/-) and control (+/+) mice between birth and adulthood. Testis weights were similar at birth in both types of mice, but after about 3 wk, the (-/-) testes remained significantly lighter, weighing only 18% of (+/+) testes on d 70. Testicular testosterone (T) content on d 1 was also similar in (-/-) and (+/+) testes, but it was 97% reduced by d 70 in the former. Likewise, testicular T production in vitro was similar in neonatal (-/-) and (+/+) testes, but became undetectable in adult (-/-) testes. The mRNA expression of cytochrome P450 side-chain cleavage, 17 alpha-hydroxylase cytochrome P450, 17 beta-hydroxysteroid dehydrogenase type III, 3 beta-hydroxysteroid dehydrogenase I (3 beta HSDI), steroidogenic acute regulatory protein, and relaxin-like factor were similar in newborn (-/-) and (+/+) testes, but became gradually very low/undetectable in (-/-) mice. The only exception was the persistently high expression of 3 beta HSDI in peritubular Leydig precursor and mesenchymal cells of the (-/-) testes at all ages. Immunohistochemistry and Western hybridization studies confirmed the above findings. In conclusion, LH action is not essential for the differentiation and function of mouse fetal Leydig cells, but, with the exception of 3 beta HSDI, the expression of the key genes of endocrine function of adult Leydig cells is dependent on LH signaling.