Endocrine Abstracts

The human foetal adrenal gland (HFA) comprises of two distinct zones; the foetal zone (FZ) and the definitive zone (DZ). The subcapsular DZ has been proposed to contain a population of adrenocortical progenitors that migrate centripetally to populate the FZ. Rodent studies have identified sonic hedgehog (SHH) signalling in a subcapsular non-steroidogenic progenitor population and its disruption during development causes adrenal hypoplasia. The involvement of SHH in the human foetal adrenal gland has yet to be defined. Two background leak potassium channels (K2P3.1 and K2P9.1) are expressed in the rodent adrenal gland and known to be important in aldosterone synthesis. Although their role in the HFA is unknown, K2P3.1 knockout mice exhibit disorganisation of cortical zones thus implicating K2P3.1 in adrenal development. We therefore hypothesised that a HFA progenitor cell population may be identified using markers for the DZ and the SHH pathway. Furthermore, that K2P3.1 and K2P9.1 are expressed within the HFA and play a role in gland development.

RT-PCR identified the expression of SHH pathway components (SHH, PTCH1 SMO, GLI1, GLI2, and GLI3), KCNK3 and KCNK9 within the HFA at the transcript level. K2P3.1 and K2P9.1 were found to be expressed throughout the FZ; however the adrenal capsule and small areas of the DZ appeared to be devoid of K2P3.1. Immunohistochemistry demonstrated SHH and GLI1 (SHH pathway transcriptional activator used as a marker of SHH receiving cells) expression at the periphery of the gland. Furthermore, FACS analysis identified a population of CD56 (DZ marker)- and GLI1-positive cells indicating that cells of the DZ receive a SHH signal. Additionally, inhibition of the SHH pathway with cyclopamine (10 μM), resulted in decreased Ki67-positive DZ cells. Together these data suggests that the SHH pathway is active and maybe involved in maintaining the DZ progenitor population.