Involvement of DHH and GLI1 in adrenocortical autograft regeneration in rats

Abstract

Bilateral adrenalectomy forces the patient to undergo glucocorticoid replacement therapy and bear a lifetime risk of adrenal crisis. Adrenal autotransplantation is considered useful to avoid adrenal crisis and glucocorticoid replacement therapy. However, the basic process of regeneration in adrenal autografts is poorly understood. Here, we investigated the essential regeneration factors in rat adrenocortical autografts, with a focus on the factors involved in adrenal development and steroidogenesis, such as Hh signalling. A remarkable renewal in cell proliferation and increase in Cyp11b1, which encodes 11-beta-hydroxylase, occurred in adrenocortical autografts from 2–3 weeks after autotransplantation. Serum corticosterone and adrenocorticotropic hormone levels were almost recovered to sham level at 4 weeks after autotransplantation. The adrenocortical autografts showed increased Dhh expression at 3 weeks after autotransplantation, but not Shh, which is the only Hh family member to have been reported to be expressed in the adrenal gland. Increased Gli1 expression was also found in the regenerated capsule at 3 weeks after autotransplantation. Dhh and Gli1 might function in concert to regenerate adrenocortical autografts. This is the first report to clearly show Dhh expression and its elevation in the adrenal gland.

GATA4/6 regulate DHH transcription in rat adrenocortical autografts

“…7) even though the gonad was intact in the adrenocortical autografted rat, unlike the Lhcgr upregulation found in post-gonadectomy-induced adrenal hyperplasia. Our histological analysis showed no obvious adrenal hyperplasia in the autografts 8 .…”

“…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 HH signalling pathway may participate in adrenocortical autograft regeneration as well as adrenal cortex development.…”

“…6). Dhh and Gli1 might be involved in adrenocortical cell differentiation and alter the levels of Nr5a1/Sf1 and Dax1 in adrenocortical autograft cells 8 . In contrast, the capsule cells could be under the control of other regulators such as WT1.…”

“…We calculated the amplification efficiency for each primer pair ( Table 1). Relative target gene expression levels were evaluated by the 2 −ΔΔCt method 34 using Hprt1 as an internal control according to previous our studies 8,32 . The 2 −ΔΔCt method assumes that primer amplification efficiencies are similar (usually between 90-110%) among target genes and the internal control.…”

Sonic hedgehog signaling in epithelial tissue development

“…The interactions of the three HH factors are complicated. In the adrenal gland, SHH and DHH act synergistically [114]; In the Dhh -mutant epididymis, SHH plays a compensatory role in order to maintain the stability of the signaling pathway [21].…”