| First Author | Dörner J | Year | 2017 |
| Journal | Mol Cell Endocrinol | Volume | 441 |
| Pages | 164-175 | PubMed ID | 27585489 |
| Mgi Jnum | J:263634 | Mgi Id | MGI:6095557 |
| Doi | 10.1016/j.mce.2016.08.043 | Citation | Dorner J, et al. (2017) GLI1(+) progenitor cells in the adrenal capsule of the adult mouse give rise to heterotopic gonadal-like tissue. Mol Cell Endocrinol 441:164-175 |
| abstractText | As certain strains of mice age, hyperplastic lesions resembling gonadal tissue accumulate beneath the adrenal capsule. Gonadectomy (GDX) accelerates this heterotopic differentiation, resulting in the formation of wedge-shaped adrenocortical neoplasms that produce sex steroids. Stem/progenitor cells that reside in the adrenal capsule and retain properties of the adrenogonadal primordium are thought to be the source of this heterotopic tissue. Here, we demonstrate that GLI1(+) progenitors in the adrenal capsule give rise to gonadal-like cells that accumulate in the subcapsular region. A tamoxifen-inducible Cre driver (Gli1-creER(T2)) and two reporters (R26R-lacZ, R26R-confetti) were used to track the fate of GLI1(+) cells in the adrenal glands of B6D2F2 mice, a strain that develops both GDX-induced adrenocortical neoplasms and age-dependent subcapsular cell hyperplasia. In gonadectomized B6D2F2 mice GLI1(+) progenitors contributed to long-lived adrenal capsule cells and to adrenocortical neoplasms that expressed Gata4 and Foxl2, two prototypical gonadal markers. Pdgfra, a gene expressed in adrenocortical stromal cells, was upregulated in the GDX-induced neoplasms. In aged non-gonadectomized B6D2F2 mice GLI1(+) progenitors gave rise to patches of subcapsular cell hyperplasia. Treatment with GANT61, a small-molecule GLI antagonist, attenuated the upregulation of gonadal-like markers (Gata4, Amhr2, Foxl2) in response to GDX. These findings support the premise that GLI1(+) progenitor cells in the adrenal capsule of the adult mouse give rise to heterotopic tissue. |
