Developmental regulation of pituitary growth hormone-releasing hormone receptor gene expression in the rat

The mechanisms governing age-dependent patterns of GH secretion are not well understood. Studies have shown that pituitaries of fetal and neonatal mammals are highly responsive to the stimulatory effect of GH-releasing hormone (GHRH) compared to those of mature mammals. Differential pituitary responsiveness to GHRH may, therefore, contribute to the elevated circulating GH concentrations characteristic of the perinatal period and the subsequent decline in circulating GH late in life. Age-dependent expression of GHRH-receptor (GHRH-R) would provide a cellular mechanism to direct differential somatotroph responsiveness to GHRH. Therefore, we determined the ontogeny of rat GHRH-R gene expression. We studied rats at ages that correspond to major changes in circulating GH levels: embryonic day 19.5 (of 21.5-day gestation period); postnatal days 2, 12, 30, 45, and 70; and 1 yr of age. We found that GHRH-R messenger RNA (mRNA) expression was markedly age dependent (P < 0.0003). The concentration of GHRH-R mRNA was highest on day 19.5 of gestation, the earliest age studied, and declined during the perinatal period to reach a nadir at 12 days of age. GHRH-R mRNA levels increased at 30 days of age, at time corresponding to the onset of sexual maturation, and then declined later in life. In addition, we assessed the expression of GH and Pit-1 mRNAs in pituitaries of the same age groups; we found age-dependent patterns for these transcripts that did not parallel the ontogenic pattern observed for GHRH-R mRNA. Together, these data indicate that expression of rat pituitary GHRH-R mRNA is developmentally regulated and suggest that maturation of GHRH-R may be an important determinant of somatotroph function during early development.