Although GH plays a key role in postnatal growth, prenatal growth is thought to be GH independent. However, recent data has shown GH receptor/binding protein (GHR/BP) to be present in rat fetal tissues as early as fetal stage E12. The aim of the present study was to investigate tissue- specific production of the GHR/BP messenger RNA (mRNA) and its relationship to locally transcribed insulin-like growth factor-I (IGF-I) mRNA in the fetus. We have used in situ hybridization to localize GHR/BP and IGF-I mRNAs in 16.5-, 18.5-, and 20.5-day-old rat fetuses. Furthermore, because the two promoters of the IGF-I gene differentially respond to GH stimulation, we have also investigated the presence and localization of promoter-specific IGF-I mRNAs. We found the distribution of IGF-I and GHR/BP mRNAs to be widespread but distinct during the fetal stages examined. High levels of IGF-I mRNA were found in connective tissues or their precursors, including the dermis, perichondrium, and gut. In contrast, GHR/BP mRNA exhibited three distinct patterns of distribution. First, GHR/BP mRNA was found at epithelial sites adjacent to sites of IGF-I transcription. Second, GHR/BP and IGF-I mRNAs were found to colocalize in some connective tissues, but GHR/BP mRNA levels in these sites were often lower than at other sites (i.e. epithelial) of GHR/BP gene transcription. Third, GHR/BP mRNA was also found in regions remote from IGF-I mRNA, including the nerve ganglia and inner olfactory bulb. Using promoter-specific IGF-I RNA probes, we detected only promoter 1 transcripts in all fetal tissues examined. The only exception occurred in specialized epithelial cells of the cochlea where we detected high levels of both promoter 1- and 2-derived IGF-I transcripts. We have thus demonstrated a distinct distribution of GHR/BP and IGF-I mRNAs in the developing rat fetus with coordinate expression at some sites. These findings suggest a role for GH or a GH-like peptide, acting both directly and indirectly via IGF-I, in fetal growth and development.
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