Differential expression of adrenomedullin and its receptors in newborn and adult rat thymus

Abstract

Adrenomedullin (ADM) is a hypotensive peptide, which derives from the proteolytic cleavage of pro(p)ADM and acts via two main subtypes of receptors, referred to as L1-receptor (L1-R) and calcitonin-receptor-like receptor (CRLR). While L1-R is selective for ADM, CRLR may bind either calcitonin gene-related peptide (CGRP) or ADM depending on the expression of the subtype 1 or the subtypes 2 and 3 of a family of chaperones, named receptor-activity-modifying proteins (RAMPs). There is evidence that ADM, in addition to regulating blood pressure and water and electrolyte balance, may be also involved during embryogenesis in the growth and differentiation of organs and tissues, especially of those where strong mesenchymal-epithelial interactions take place. Thymus is a linfo-epithelial organ, which undergoes a very rapid prenatal and postnatal growth, playing a pivotal role in the development of immunological defense. Hence, it appeared worthwhile to investigate the expression of ADM system in the newborn (3-day-old) rat thymus as compared to adult (3-month-old) animals. Reverse transcription (RT)-polymerase chain reaction (PCR) allowed the detection of the specific mRNAs of pADM and peptidyl-glycine alpha-amidating monooxigenase (PAM), the enzyme which converts immature ADM to the mature peptide, in both newborn and adult rat thymuses. PAM expression was markedly higher in newborn animals, which accords well with the more elevated concentrations of ADM measured by RIA in newborn than adult rat thymuses. L1-R, CRLR, RAMP1 and RAMP2 mRNA were detected in both groups of rats, and with the exception of RAMP1, the expression was markedly higher in newborn than adult rat thymus. RAMP3 mRNA was present only in the thymus of newborn animals. Collectively, the present findings indicate that ADM system is up-regulated in newborn rat thymus, thereby making it likely that ADM may be involved in the thymus growth and in the development of immunological defense mechanisms.