title: Altered growth hormone-releasing hormone mRNA expression in transgenic mice with excess or deficient endogenous growth hormone.
abstract: Hypothalamic expression of growth hormone-releasing hormone (GHRH) mRNA was examined in two transgenic mouse models displaying excess or deficient endogenous GH. Transgenic dwarf mice bore a gene construct consisting of the rat growth hormone (GH) promoter fused to a diphtheria toxin A chain structural gene (DT-A); the GH promoter restricted DT-A expression to endogenous GH-producing cells, which were destroyed. GH was undetectable in either the pituitary or the peripheral circulation (Behringer et al., Genes Devel. 2: 453-461, 1988). Transgenic giant mice carried a construction joining the metallothionein promoter to the human GHRH structural gene, which stimulated endogenous pituitary GH production (Hammer et al., Nature 315: 413-417, 1985). In situ hybridization to GHRH mRNA in transgenic dwarf, giant, and nontransgenic controls was performed using single-stranded RNA probes generated from cloned mouse GHRH cDNA. Hybridization to GHRH mRNA was limited to the neurons of the hypothalamic arcuate nucleus (ARC). Autoradiographic densities on X-ray films were quantified by computerized image analysis. There was an increase in GHRH signal intensity in the dwarfs (282 +/- 20 units; mean +/- SEM) relative to that measured in control animals (107 +/- 8 units; P < 0.001), while giant mice had decreased signal (42 +/- 7 units; P < 0.001) in the ARC. The present studies demonstrate that increase in GHRH mRNA expression accompanies GH deficiency, while a decrease in GHRH mRNA accompanies GH excess, suggesting both positive and negative feedback upon steady-state mRNA levels in hypophysiotropic neurons by target pituitary hormone.
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana 70118; and Department of Anatomy, Tulane University School of Medicine, New Orleans, Louisiana 70112.
authors.forename: D L
authors.initials: DL
authors.lastname: Hurley
authors.forename: C J
authors.initials: CJ
authors.lastname: Phelps