Rapid Maturation of the Endocrine Growth Axis in the Marsupial During Development.

Abstract

Growth hormone is essential for post-natal growth and its actions are triggered by the upregulation of hepatic growth hormone receptors (GHRs) after birth in eutherian mammals. In utero, fetal growth is largely driven by the availability of nutrients that control the relative levels of insulin and insulin-like growth factors (IGFs). This study examined expression of hepatic GHR, IGF-1, IGF-2 and IGF binding protein-3 (IGFBP-3) from late fetal stages of pregnancy through pouch life to weaning using the tammar wallaby. The advantage of the tammar wallaby is that it gives birth to an altricial young that is only 0.1% of adult female size, essentially an exteriorized fetus. After 9 months of pouch life the young exits the pouch, a time equivalent to birth in precocial eutherian mammals. We cloned GHR, IGF-1, IGF-2 and IGFBP-3 using RT-PCR and used quantitative PCR to determine the relative change in expression of these genes in male and female fetuses one day before birth and young at 15, 45, 70, 100, 150 and 250 days (d) post-partum (pp) and adults (n=7-10 per stage). There was significant protein homology between tammar genes and those of mouse and man (62 and 68% for GHR, 79 and 85% for IGF-1, 63 and 65% for IGF-2, 69 and 71% for IGFBP-3 respectively). Hepatic GHR and IGF-1 expression increased gradually in both males and females from birth to d150pp, after which levels reached a plateau (ANOVA P<0.0001).IGFBP-3 and IGF-2 expression rose to a peak about d70-100pp then fell at later ages of lactation and in adults, with generally lower levels in females than males (ANOVA P<0.01 for age and P<0.05 for sex). The age-related changes in expression of these genes probably reflect a conserved role in development, while the sex-specific differences may correlate with some of the growth and developmental differences, observed between males and females especially in the phallus.