Abstract
Adrenal cortex autotransplantation with ACTH stimulation may be an alternative therapy for patients with bilateral adrenalectomy to avoid adrenal crisis, but its underlying mechanism has not been elucidated. Previously, we detected Dhh upregulation in rat adrenocortical autografts after transplantation. Here, we investigated potential regulators such as Gata4, Gata6, Sry and Sox9 which affect Dhh transcription in adrenocortical autografts with or without ACTH stimulation. In ACTH-stimulated autografts, Gata4 and Gata6 were downregulated compared to control autografts. This response was linked to rDhh repression. A reporter assay using the upstream region of rDhh and a GATA binding motif revealed that rDhh promoters were significantly upregulated by co-transfection with Gata4 or Gata6 or both. Sry and Sox9 expression in autografts with or without ACTH stimulation were verified by PCR and RNAscope analyses. The ovarian differentiation factors Foxl2 and Rspo1 were also upregulated in the autografts. Gata4 and Gata6 were found to be significant factors in the regulation of rDhh expression and could be associated with adrenocortical autograft maintenance. Gonadal primordia with bipotential testicular and ovarian functions may also be present in these autografts.
Highlights
Adrenal cortex autotransplantation with ACTH stimulation may be an alternative therapy for patients with bilateral adrenalectomy to avoid adrenal crisis, but its underlying mechanism has not been elucidated
In the search for factors affecting post-transplant adrenocortical autograft remodelling and regeneration, we found that Dhh was upregulated and Shh was downregulated in the regeneration step of rat adrenocortical autograft[8]
The regulation of Dhh transcription during gonadal development involves transcription factors such as Wt1, Gata[4], Gata[6], Sox[9] and Sry[9,10]. We examined whether they affect Dhh transcription in adrenocortical autografts
Summary
Adrenal cortex autotransplantation with ACTH stimulation may be an alternative therapy for patients with bilateral adrenalectomy to avoid adrenal crisis, but its underlying mechanism has not been elucidated. We investigated potential regulators such as Gata[4], Gata[6], Sry and Sox[9] which affect Dhh transcription in adrenocortical autografts with or without ACTH stimulation. Sry and Sox[9] expression in autografts with or without ACTH stimulation were verified by PCR and RNAscope analyses. After ACTH stimulation for 2 h, Vegfa showed a 1.8-fold increase in the adrenal gland compared with that in the intact group (Fig. 1).
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