Dedifferentiation of glomerulosa cell to transitional cell phenotype during adrenal regeneration in rats

Following adrenal enucleation with removal of the inner cortex and the medulla, the adrenal cortex regenerates from a capsular-glomerulosa cell remnant A distinct cellular transitional zone (TZ) exists adjacent to the zona glomcrulosa that does not express either cytochromc P450 aldosterone synthase (P450aldo) or 116 hydroxylase (P450116) protein. Since the TZ may provide progenitor cells for regeneration, in_sun hybridization histochemistry was used to monitor TZ-like changes in the capsularglomerulosa remnant after adrenal enucleation. Transitional zone ecus were defined as cells negative for P450aldo and P450116, but positive for cytochrome P450 side chain cleavage (P450scc) mRNA. Rats (n=4/group) underwent unilateral adrenal enucleation with contralateral adrenalectomy and were killed at 10, 20 or 30 days post surgery. Cryostat sections of adrenals were hybridized as a group with 35S-labeled oligonucleotide probes and detected by emulsion autoradiography. At 10 days, cells adjacent to the capsule showed an absence of P450aldo and P450116 mRNA, but the presence of P450scc mRNA. By 20 and 30 days, cells near the capsule expressed P450aldo and P450scc mRNA, but not P450116 mRNA. These results show that adrenal enucleation results in the loss of the glomerulosa cell phenotype concomitant with the expansion of the TZ. These data suggest that during adrenal regeneration glomerulosa cells dedifferentiate to a transitional cell phenotype. The expansion of the TZ may provide additional progenitor cells for adrenal regeneration. Supported by NIH GM 50150.