Localization of growth hormone receptor/binding protein messenger ribonucleic acid (mRNA) during rat fetal development: relationship to insulin-like growth factor-I mRNA.
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 parameters 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 of GH or a GH-like peptide, acting both directly and indirectly via IGF-I, in fetal growth and development.
Edmondson
S R
SR
Centre for Hormone Research, Royal Children's Hospital, Parkville, Victoria, Australia.
Werther
G A
GA
Russell
A
A
LeRoith
D
D
Roberts
C T
CT
Beck
F
F
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D003238:Connective Tissue / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism*; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008969:Molecular Sequence Data; D011247:Pregnancy; D015347:RNA Probes; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D011986:Receptors, Somatotropin / Q000235:genetics*
D002352:Carrier Proteins; D015347:RNA Probes; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; C051815:somatotropin-binding protein