Studies on prolactin and growth hormone gene expression in the pituitary gland of spontaneous dwarf rats

Abstract

The spontaneous dwarf rat (SDR) is a newly established experimental model for pituitary dwarfism with an autosomal recessive mode of inheritance. GH and PRL gene expressions were studied in the pituitary gland of this animal. Immunocytochemistry failed to detect any immunoreactive GH cells in SDR pituitary gland, whereas numerous PRL cells were encountered throughout the anterior lobe. Similarly, GH was not detectable in the pituitary cytosol from SDR of 7, 20, and 80 days of age. PRL of the same mol wt as the authentic rat PRL was found in the pituitary glands in all SDRs examined. Since these results were thought to be due to the absence of GH mRNA in the SDR's pituitary gland, we attempted to detect GH mRNA by dot hybridization. Very small amounts of GH mRNA were found in the pituitary glands of both male (2.6% of normal) and female (6.0% of normal) SDRs. Reduced levels of PRL mRNA were also found in the pituitary glands of male (50%) and female (30%) SDRs. Northern blot analyses of total RNA extracts revealed that the GH mRNA of the SDR was similar in size to the mature GH mRNA found in the pituitary glands of control rats. PRL mRNA from the SDR also migrated to the same position as normal PRL mRNA. Nuclear DNA preparations were prepared from normal and SDR livers, and the genomic organizations of the GH and PRL genes were examined using restriction mapping. The DNA fragment length patterns obtained with the cDNA probes for GH or PRL using several restriction enzyme digestions were identical. The results suggest that the GH deficiency in SDR is not due to a gross deletion or rearrangement of the GH gene. It is proposed that SDR may be an excellent experimental model for the study of isolated GH deficiency in the human.