Endocrine Abstracts

Introduction: The Sonic hedgehog (Shh) pathway is an evolutionarily conserved signalling pathway, playing an essential role during embryonic development. Murine studies have shown the importance of Shh in the growth of the adrenocortical primordium. Shh expression has previously been described in relatively undifferentiated sub-capsular cells in the developing rodent adrenal, however the organisation of the human foetal adrenal (HFA) is unique. This novel study aimed to describe the developmental expression patterns of Shh and its pathway components in the early developing HFA.

Methods: The expression of Shh, and pathway components, Patched-1 (Ptch-1) and Gli1, was demonstrated in H295R cells, primary HFA cells, and HFA tissue using PCR. Quantitative real-time PCR (qPCR) was performed on HFA tissue cDNA from a range of gestational ages to explore the temporal relative expression of Shh and pathway components. The spatial expression of Shh-expressing and receiving cells was determined using non-radioactive in situ hybridisation.

Results: Shh and Shh signalling pathway components were shown to be expressed in the developing human adrenal. Relative Shh expression in the HFA cortex was seen to decrease in the first trimester with increasing gestation. Cells expressing Shh and Gli1 were seen to localise at the periphery of the adrenal gland and in the overlying capsular mesenchyme.

Conclusion: These studies reveal that the Shh pathway is active during HFA development. For the first time it is demonstrated that components of the Shh signalling pathway are expressed in the first trimester human foetal adrenal at mRNA level, and expression appears to be regulated in a spatio-temporal manner. This research furthers our understanding of the molecular mechanisms governing adrenal development. The function of Shh signalling in human adrenal development is unknown but is hypothesised to exhibit similarly crucial roles demonstrated in previous animal studies.