Ontogeny of growth hormone releasing hormone and insulin-like growth factors-I and -II messenger RNA in rat placenta

Hypothalamic growth hormone releasing hormone (GHRH) stimulates pituitary growth hormone secretion, which is essential for normal postnatal growth. Reports of an immunoreactive and biologically active GHRH-like peptide in placenta led us to investigate placental expression of GHRH mRNA. Placentas from d 19 gestation fetal rats were assayed for GHRH-like peptide by ELISA and for GHRH mRNA. Placenta GHRH-like peptide levels averaged 3.7 ± 0.2 ng/g tissue. Dot-blot hybridization revealed the presence of GHRH mRNA in rat placenta in quantities greater than those of the message in rat hypothalamus. Northern gel analysis of poly-A enriched RNA was used to evaluate the specificity of GHRH mRNA hybridization and to determine the size of the placental mRNA. Placental and hypothalamic GHRH mRNA were of nearly identical size, although placental RNA had a broad band of hybridization that extended below that seen in hypothalamus. Further confirmation of homology between placental and hypothalamic GHRH mRNA was determined by an RNAse protection assay, in which a placental protected fragment was identical in size to that resulting from protection of the hypothalamic complementary RNA. The ontogeny of GHRH mRNA in rat placenta was determined by dot-blot hybridization. The message was detected at the earliest date examined, d 7, and increased more than 2-fold by d 14 and 5-fold by d 17. The ontogeny of IGF-I and IGF-II mRNA in placenta was also determined. IGF-I mRNA was detected at all gestational dates examined, but was highest on d 10, whereas IGF-II mRNA was not detectable on d 7 or 10 but was present on d 14, 17, and 20. We conclude that GHRH mRNA is present in rat placenta at least from d 7 of gestation. Placental expression of GHRH mRNA is concurrent with maximal expression of placental IGF-II, but not IGF-I mRNA. The similar time course of expression for GHRH mRNA and IGF-II leads us to speculate that they may have related functions in the last week of rat gestation.