Rat Adrenal Transplants are Reinnervated: An Invalid Model of Denervated Adrenal Cortical Tissue

Abstract

Adrenal autotransplantation is a widely used approach to investigate the potential for neural modulation of adrenal cortical function. It is believed that regenerating adrenal transplants are not reinnervated, thereby providing a model to investigate adrenal function in the absence of neural modulation. However, the hypothesis that adrenal transplants become reinnervated has not been directly tested. The purpose of the present study was to characterize the time course, extent, and nature of the reinnervation of the regenerating adrenal transplant and to assess whether the recovery of steroidogenic function and enzyme expression correlates temporally with the presence of innervation. Using immunohistofluorescent detection of tyrosine hydroxylase (TH), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP), the innervation of regenerating adrenals was assessed 14-30 days after transplantation of adrenal capsules beneath the kidney capsule in rats. Extensive reinnervation by TH-, NPY-, and VIP-positive fibres was present by 14 days after transplantation including regions of the adrenal capsule and cortex, with only minimal reinnervation by CGRP-positive fibres up to 30 days. TH- and NPY-positive chromaffin cells were also observed in the regenerating transplants. In addition, there was marked recovery of steroidogenic function and steroidogenic enzyme expression up to 30 days. The finding that nerve fibres are present in the transplants during the re-establishment of steroidogenic function and enzyme expression suggests that innervation may modulate the regeneration and functional recovery of adrenal transplants. In an attempt to prevent reinnervation of transplants, adrenal capsules were autotransplanted to denervated kidneys. Immunohistochemical analysis showed that, despite extensive denervation of the kidney tissue, the reinnervation and regeneration of the adrenal transplants still occurred. These data demonstrate the marked capacity of the regenerating adrenal to become reinnervated and reinforces the conclusion that adrenal transplants are an invalid model of denervated adrenal cortical tissue.

Innervation of ectopic endometrium in a rat model of endometriosis

“…These findings are similar to those of auto-or syngeneic transplants of other organs and tissues in experimental animals. For example, sympathetic efferent reinnervation is commonly observed in transplants of the parathyroid gland (21), pancreatico-duodenum (22), lung (23), heart (24), and adrenal gland (25). Sensory innervation, although not studied as often, is also observed, for example in transplants of lung (26,27) and heart (28).…”

“…Sensory innervation, although not studied as often, is also observed, for example in transplants of lung (26,27) and heart (28). Sensory innervation is sometimes sparse, for example in transplants of the parathyroid and adrenal glands (21,25), and may relate to the site of implantation as noted by Korsgren et al (29), who found that the extent of sensory reinnervation of pancreatic islet cells was markedly different for implants in the spleen, liver, or renal subcapsule.…”

Adrenal glucocorticoids have a key role in circadian resynchronization in a mouse model of jet lag

“…To control for the transplantation procedure, WT animals received their own (i.e., WT) adrenal transplants following adrenalectomy. After the surgery, animals were allowed to recover for 8 weeks under standard LD conditions to ensure complete reinnervation of the transplanted tissues (66).…”

Differentiation and Regeneration of Adrenal Tissues: An Initial Step toward Regeneration Therapy for Steroid Insufficiency

“…While adrenal cell transplantation into the subcapsular region of the kidneys leads to good regeneration of adrenal cortical tissue, cell transplantation into the skin has also been reported to be possible when a collagen gel is used [29]. Although previously denied, autologous transplantation of adrenocortical cells or tissues does actually cause innervation, which is correlated with the degree of recovery of the steroid production [30]. Crawford et al demonstrated that stable SF-1 expression in ESCs resulted in a steroidogenic capacity and adenosine 3,5-cyclic monophosphate (cAMP) or retinoic acid-dependent inducibility of cytochrome P450scc, leading to progesterone production [31].…”