Davis, Kevin T.
(2004)
The Role of Gap Junctions in Adrenal Gland Function.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
This thesis explores the theory that gap junctions play a role in adrenocortical homeostasis and function. To test this hypothesis, gap junction mediated communication was investigated in the intact adrenal gland. In addition, to determine the impact of altered adrenal trophic state on gap junction distribution and expression, adrenal glands from hypophysectomized mice as well as normal and neoplastic human adrenal tissues were evaluated. Gap junction mediated intercellular communication was done in primary mouse adrenal glands using a modified Lucifer Yellow dye communication assay. Dye communication showed that the adrenal cortex was communication competent and that functional cell-cell communication was directly related to the abundance of connexin 43 expression. There was an absence of dye communication in the outer cortical zona glomerulosa (ZG) that was contrasted by a high level of communication in the inner zones of the zonae fasciculata/reticularis (ZF/ZR).The removal of the endogenous pituitary derived ACTH stimulus by hypophysectomy resulted in a significant loss of connexin 43 expression in the ZF/ZR that was associated with a diminished trophic state. The loss of connexin 43 expression was concurrent with features associated with a diminished functional state of the gland including loss of lipid droplets and reduced expression of the ZG specific cytochrome P450 aldosterone synthase (P450 aldo). A comparison of adrenal glands from connexin 43 deficient mice (Cx 43 -/-) demonstrated several features that were similar to those observed in hypophysectomized mice, including glandular atrophy and reduced P450 aldo expression in the ZG.Connexin 43 expression and distribution in the normal human adrenal gland was identical to that previously described in the adrenal glands from other mammals. Connexin 43 expression was abundant in the ZF/ZR and nearly absent from the parenchymal cells of the ZG. Immunocytochemial analysis of neoplastic tissues showed that benign (adenoma) and malignant (carcinoma) neoplasms lost 30% and 90% respectively, of their connexin 43 expression in the ZF/ZR when compared to normal tissues. The data presented here demonstrate that connexin 43 expression is related to physiological changes that affect adrenal trophic state and suggest that gap junction mediated cell-cell communication is involved in the function of the adrenal cortex. Furthermore, because connexin 43 deficient animals also exhibit glandular changes consistent with a diminished state of the adrenal gland, it supports a role for proper gap junction expression in adrenal cortex development and function.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
24 June 2004 |
| Date Type: |
Completion |
| Defense Date: |
24 October 2003 |
| Approval Date: |
24 June 2004 |
| Submission Date: |
7 May 2004 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Faculty of Arts and Sciences > Biological Sciences |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
adrenal cortex; connexins; gap junctions; intercellular communicatiion |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-05072004-130322/, etd-05072004-130322 |
| Date Deposited: |
10 Nov 2011 19:44 |
| Last Modified: |
15 Nov 2016 13:43 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/7817 |
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