Perturbation of differentiated functions in vivo during persistent viral infection. III. Decreased growth hormone mRNA.

Lymphocytic choriomeningitis virus (LCMV) persistent infection that results from the inoculation of C3H/St newborn mice causes growth hormone (GH) deficiency and associated disease characterized by both reduced weight and serum glucose levels. Molecular analysis of pituitary nucleic acids shows GH deficient mice have, on average, fivefold reduced levels of GH mRNA although the histopathology of such GH producing cells is normal. Northern blots indicate that the length of GH mRNA is comparable in the GH deficient, virus infected mice and the GH normal, uninfected age-matched controls. Hence, truncated GH mRNA cannot account for hormonal defect. Mice infected congenitally through mating of persistently infected parents have normal growth and blood glucose levels. GH mRNA levels in pituitaries of these mice are equivalent to those of uninfected age-matched controls but significantly greater than those seen in neonatally infected GH deficient mice. Although infectious virus titers in the sera are equivalent in congenitally and neonatally infected age- and sex-matched mice, virus titers are significantly lower in pituitaries and brains of the congenitally infected mice when compared to neonatally inoculated mice. Additionally, the number of GH-producing pituitary cells expressing viral proteins is less in congenitally infected mice relative to those in neonatally inoculated mice. Hence there is a direct association between viral replication in GH-producing cells, lowered GH mRNA, and GH deficiency.