|Chase, Chadwick - Chad|
|Hammond, Andrew - Andy|
Submitted to: Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/15/2000
Publication Date: N/A
Interpretive Summary: Growth hormone receptor deficiency (GHR) in a variety of species, including humans (Laron dwarfism, has been associated with abnormal growth and small adult size. We previously identified a miniature condition that resulted in mature cattle of approximately 70% height and weight of those of normal size. For normal growth, growth hormone (GH) produced in the body travels in the blood and binds to the GHR in liver and other tissues and turns on the production of another growth regulating hormone, insulin-like growth factor-I (IGF-I). Based on pedigree analyses, birth weight, mature size, and blood hormone concentrations (GH:IGF-I ratio) we conducted a study to further characterize GHR and IGF-I in our miniature cattle. The miniature cattle had similar GHR size (mRNA) and sequence (cDNA) as control cattle. As expected, liver IGF-I (mRNA) in miniature cattle was only 12% of the amount in control cattle. The amount of total GHR and the inducible, liver specific GHR (GHR 1A mRNA) were also decreased in miniature cattle. In summary, our miniature cattle that display characteristics similar to Laron dwarfism did not arise from a gene mutation in the GHR. Rather, underexpression of inducible, liver specific GHR 1A but not other GHR variants in liver were associated with underexpression of liver IGF-I and small mature size. Full expression of GHR 1A in liver, therefore, may be an absolute requirement for normal growth.
Technical Abstract: Mutations within the growth hormone receptor (GHR) gene that lead to an inactivated or truncated GHR protein cause abnormal growth and small adult size in a variety of species (Laron dwarfism). We studied a line of miniature Bos indicus cattle that have phenotypic (small mature size) and endocrine (increased blood GH and decreased blood IGF-I concentrations) similarities to Laron dwarfs. Liver mRNA from miniature and control cattle was used to amplify GHR cDNA by reverse transcriptase polymerase chain reaction. The miniature cattle had GHR mRNA size (determined by Northern blot) and cDNA sequence that were similar to control cattle and, therefore, were unlike most Laron dwarf genotypes in which the GHR gene is mutated. Amounts of mRNA from liver as well as muscle (superficial neck and longissimus) were analyzed by ribonuclease protection assay for IGF-I, total GHR, GHR 1A (inducible, liver-specific GHR mRNA) and GHR 1B (constitutive GHR mRNA). Four control and five miniature bulls were tested. As expected, liver IGF-I mRNA was decreased in the miniature cattle (approximately 12% of control). The amount of the total GHR as well as GHR 1A mRNA were also decreased in liver (17% and 19% of control, respectively). Other GHR mRNA, including GHR 1B mRNA, were similar for miniature and control cattle.