AMES DWARF MICE EXHIBIT SOMATOTROPE COMMITMENT BUT LACK GROWTH HORMONE-RELEASING FACTOR RESPONSE

Ames dwarf mice have a recessive defect that results in affected mice (df/df) with extremely hypocellular anterior pituitaries that generally lack somatotropes, lactotropes,and thyrotropes. We report detection of rare foci of GH(+) cells by immunocytochemistry, suggesting that some commitment to a somatotrope cell fate can occur in the pituitaries of df/df mice. A role for GHRF in regulating somatotrope proliferation is well documented. It has been shown that expression of human GHRF (hGHRF) in transgenic mice resulted in increased somatic growth and somatotrope hyperplasia over nontransgenic littermates. To assess whether overexpression of GHRF during ontogeny might elicit a physiological response in df/df mice, we generated df/df mice expressing the hGhrf transgene. Although the somatic growth of transgenic df heterozygotes was dramatically increased over that of nontransgenic littermates, df/df mice were refractory to excess GHRF. No GHRF receptor (Grfr) transcripts were detectable in df/df fetuses or adult mice by in situ hybridization analysis. In contrast, Grfr expression is detected by e16.5 in df/ + mice. The lack of Grfr expression in df/df fetuses may account for their lack of response to GHRF and implies that the elf gene product is required before e16.5.