Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/23/1999
Publication Date: N/A
Interpretive Summary: The positive effects of growth hormone (GH) are dependent on the presence of molecules called receptors, which recognize GH. The liver is one of the important target organs for GH. GH stimulates the liver to produce a hormone called insulin-like growth factor-1 (IGF-1), which is a stimulator of growth. At the level of the DNA, the RNA for the GH receptor (GHR) can be produced in several ways. This results in two main types of GHR RNA, GHR1A and GHR1B. At present, there is little information on the control of production or relative biological importance of these two forms of GHR. The objective of this study was to evaluate the effects of age and GH treatment on liver GHR1A and GHR1B in pigs. While GHR1B was found in a variety of tissue types, GHR1A was produced only in liver. GHR1A was not detectable in the early neonatal period, but appeared as the young pig increased in age. The lack of GHR1A in the neonatal pig could explain the recognized resistance of very young pigs to GH treatment. GH treatment did not affec GHR levels in young developing pigs, but did reduce GHR1A in pregnant sows. The production of liver GHR1A, but not GHR1B, was significantly related to the production of IGF-1 in all cases. These results suggest that GHR1A may be important in the regulation of IGF-1 production and growth in response to GH. A better understanding of how GH works is important in developing strategies and new technologies for improving swine production efficiency.
Technical Abstract: The 5' untranslated sequence (exon 1) of growth hormone receptor (GHR) mRNA is heterogeneous because GHR mRNA transcription is initiated from multiple promoters. Most GHR mRNA arise from GHR Promoter 1 (P1) and GHR P2 that transcribe GHR1A and GHR1B mRNA, respectively. The objective of the present study was to characterize the expression of GHR1A and GHR1B mRNA in npigs. The porcine GHR1A and GHR1B cDNA were cloned by reverse transcription and polymerase chain reaction. The amount of GHR1A and GHR1B mRNA was determined by using a ribonuclease protection assay with specificity for exon 1. Tissue specificity of GHR1A and GHR1B mRNA was determined by comparing liver with muscle and reproductive tissues. The developmental regulation of GHR1A and GHR1B mRNA was tested in castrated (1 to 42 d of age) and intact (21 to 77 d of age) male pigs. Regulation of GHR1A and GHR1B mRNA by GH was tested in intact male pigs (21 to 77 d of age) as well as mature pregnant sows. Porcine liver expressed both GHR1A and GHR1B mRNA. Other tissues including longissimus muscle, uterus, and ovary expressed GHR1B mRNA but not GHR1A mRNA. The liver of castrated male pigs expressed GHR1B mRNA at all ages but did not express GHR1A mRNA until 42 d of age (2 of 6 pigs). The liver of intact male pigs expressed GHR1A mRNA by 21 d of age. In pregnant sows, GHR1A mRNA in liver was down-regulated by GH. In each experimental model, GHR1A mRNA but not GHR1B mRNA was positively correlated with liver IGF-1 mRNA or serum IGF-1 concentrations. In conclusion, tissue-specific and developmental regulation of GHR was found for GHR1A but not GHR1B mRNA. These data suggest that the regulation of GHR1A mRNA is the primary mechanism controlling liver IGF1.