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Cushing's Syndrome and Fetal Features Resurgence in Adrenal Cortex–Specific Prkar1a Knockout Mice

Figure 4

Morphological defects and progressive hyperplasia in AdKO adrenals.

(A–L) Adrenals were collected from WT (A–C and G–I) and AdKO (D–F and J–L) parous females aged of 5, 10 and 18 months and stained with haematoxylin and eosin. AdKO adrenal cortex presented progressive centrifugal expansion of large eosinophilic cells, indicated by a double arrow in (D–F). In the top panels, squares delineate the higher magnifications shown in (G–I) for WT and (J–L) for AdKO adrenals. Insets, higher magnification illustrating the increased cell area of expanding eosinophilic cells compared to normal spongiocytes. (M–O) Adrenal sections from 18-month-old mice double-stained for β-catenin, a zona glomerulosa marker (in green) and for Sf1, a steroidogenic marker (in red). Nuclei were stained by Hoechst in blue. (M) WT adrenal cortex. (N) AdKO adrenal cortex. (O) Higher magnification of (N), where hyperplastic small spindle-shaped, basophilic cells lacking both staining are enlightened by arrows. (P–R) Immunodetection of the pre-tumoural marker Gata-4 in adrenal sections of parous 18-month-old females. (P) WT. (Q–R) AdKO. (R) The square delineates the higher magnifications shown in the right. Top panel: Gata-4 staining. Lower panel: same section with haematoxylin and eosin counter-staining. M, Medulla; C, Cortex; F, zona fasciculata; G, zona glomerulosa; Ca, Capsule; Scale bars, 50 µm.

Figure 4

doi: https://doi.org/10.1371/journal.pgen.1000980.g004