Adrenomedullin and its receptors are expressed in the zona glomerulosa of immature and adult rat adrenals: evidences of upregulation of ADM system in immature glands.

Evidence has been provided that adrenomedullin (ADM) stimulates the proliferative activity of adult rat adrenal zona glomerulosa (ZG). However, the selective ADM receptor antagonist ADM(22-52), although being able to block ADM effect, was per se ineffective. In contrast, in the companion paper, we showed that ADM(22-52) depresses the proliferation rate of ZG in 20-day-old rats, suggesting the involvement of endogenous ADM system in adrenal maturation. Hence, we investigated by semiquantitative reverse transcription-polymerase chain reaction and radioimmune assay the expression of ADM system in adult and immature rat ZG. ProADM mRNA and ADM-immunoreactivity were both more elevated in immature- than adult-rat ZG. Plasma ADM concentration did not show significant age-related differences. ADM acts via two subtypes of ADM(22-52)-sensitive receptors: the L1 receptor (L1-R) and the calcitonin-receptor-like-receptor (CRLR), the latter behaves as selective ADM receptor only in the presence of the receptor-activity-modifying proteins (RAMPs)2 and 3. L1-R expression was enhanced in immature rat ZG, while CRLR and RAMP(2,3) expression did not display significant differences. It is concluded that the endogenous ADM system located in the ZG is upregulated in immature rats, and plays an important autocrine-paracrine role in the maintenance of the elevated growth rate during adrenal maturation.