Functional biology of the primate fetal adrenal gland: advances in technology provide new insight.

1. The main aim of the present review is to summarize recent experimental data from human and non-human primate models that have identified factors essential for adrenal development and other factors that may determine the regulation of the specific structural organization and function of the adrenal gland. 2. The fetal adrenal cortex has two morphologically distinct zones, with the outer definitive zone being comprised of tightly packed small cells, which appear to be steroidogenically quiescent until late gestation, and the inner fetal zone, which appears to be steroidogenically active throughout gestation. 3. In the primate fetus, growth of the adrenal gland involves hyperplasia, hypertrophy, migration and senescence. Cells appear to proliferate in the external portion of the definitive zone and then move centripetally and become non-proliferative in the fetal zone, where they acquire their steroidogenic capacities. 4. A variety of new technologies has been used to identify zonal-specific markers of the cortical zones within the developing human fetal adrenal gland. On microarray, 67 transcripts showed a minimum of a 2.5-fold difference between the fetal and adult adrenal gland. The vast majority of these genes had not been studied in relation to adrenal gland development or function. In combination with techniques such as laser capture microdissection, which has allowed the isolation of fairly pure zone-specific cell populations from the human fetal adrenal cortex, we can begin to unravel the complex interactions regulating adrenal growth and functional differentiation.