GH gene expression in the submaxillary gland in normal and Ames dwarf mice

Abstract

High local GH-releasing hormone (GHRH) levels are capable of inducing transdifferentiation in salivary cells to synthesize GH. However, the factors implicated in this process remain unknown. To study this subject, normal and Ames dwarf mice were implanted in the submaxillary gland with a slow release pellet releasing 21 microgram GHRH (1-29)-NH(2)/day for 2 months. Control animals received placebo pellets at the same site. After 60 days, heart blood was collected and submaxillary glands were removed. Circulating levels of GH and IGF-I were significantly decreased (P<0.05) in dwarf mice in comparison with controls, and GHRH treatment did not modify either of these two parameters. Controls carrying GHRH pellets showed a significantly higher GH content (P<0.05) in the submaxillary gland than the placebo-treated normal mice. There were no differences between the IGF-I concentrations of placebo- and GHRH-treated salivary tissue from normal mice. Analysis of GH mRNA by RT-PCR followed by Southern blot revealed that GH transcripts were present in the salivary gland samples carrying the placebo pellets in both normal and dwarf mice. The expression of GH was significantly (P<0.05) increased by the GHRH pellets in salivary tissue from normal mice, but not in submaxillary glands from dwarf mice. Pit-1 mRNA was not detected in the GHRH-treated glands of normal and dwarf mice by RT-PCR or by Southern blot. Using these highly sensitive methods, we have been able to detect the transcription of both GH and Pit-1 in pituitaries from Pit-1-deficient Ames dwarf mice. The present experiment demonstrates that salivary tissue synthesizes GH when it is exposed to the influence of GHRH. Both basal and GHRH-induced salivary GH expression appear to be independent of Pit-1.

Extrapituitary growth hormone

“…After GHRH treatment, GH mRNA is also readily detectable by southern blotting and in situ hybridization. GH and GH mRNA are also present in the salivary glands of GHRH-treated and untreated normal and Ames dwarf mice, independently of the Pit-1 transcription factor required for pituitary GH expression [178]. Roles for GH in salivary function are largely unknown although the absence of granular duct cells in glands of transgenic mice expressing a GH-antagonist and in GHR knockout mice [179] suggests GH involvement in the differentiation of this gland and its production of epidermal growth factor.…”

“…It is therefore not surprising that GH expression is widespread and in many tissues, although GH expression is not pit-1-dependent in all tissues [311]. The expression of GH in pituitary and extrapituitary tissues may therefore be differentially regulated, as indicated by the expression of GH in the hippocampus and salivary glands of pituitary GH-deficient dwarf mice [7,8,178], in which GH deficiency results from a mutation in prop-1, an upstream transcription factor for Pit-1. GH expression in immune tissues may similarly be differentially regulated from that in the pituitary gland [312].…”