Year: 2004
Type: dissertation
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.
Author: Kevin T. Davis
Language: English
Topic: Connexins and lens biology
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2146638155