Hypophysectomy Results in a Loss of Connexin Gap Junction Protein from the Adrenal Cortex

Abstract

To test the hypothesis that gap junctions are dependent on the tropic state of the adrenal gland, the effect of hypophysectomy on connexin 43 (alpha1-Cx43) gap junction protein occurrence and distribution was examined in mice. Gap junction protein occurrence was assessed with immunohistochemical techniques. In the adrenal gland from intact animals, alpha1-Cx43 gap junction protein was detected in the zonae fasciculata(ZF) and reticularis (ZR) while only a few alpha1-Cx43 gap junction plaques were found connecting zona glomerulosa(ZG) cells. Hypophysectomy led to a profound atrophy of the cortex which was more marked in the inner zones (zonae fasciculata and reticularis) than in the zona glomerulosa. There was a time dependent loss of alpha1-Cx43 gap junction protein in the adrenal cortex after hypophysectomy. At 33 day following hypophysectomy there was a two fold decrease in gap junctions in the zona fasciculata while the average gap junction plaque size was not different than the size seen in control animal adrenal glands.. ACTH (1U/gm body weight) treatment in hypophysectomized animals increased the number of gap junction plaques in the zona fasciculata. Hypophysectomy led to diminished alpha1-Cx43 gap junction expression in the zona fasciculata which could be restored by ACTH treatment. Because altering the tropic state of the adrenal glands via hypophysectomy leads to a reduction in gap junction number, it can be suggested that control of gap junction expression in the adrenal gland is hormone dependent and linked to adrenal gland function.

Distribution of cells expressing Jun and Fos proteins and synthesizing DNA in the adrenal cortex of hypophysectomized rats: regulation by ACTH and FGF2

“…The results presented herein corroborate those of studies reporting that hypophysectomy tends to cause atrophy of the inner zones of the adrenal cortex (Deane 1962;Tchen et al 1977;Ceccatelli et al 1995;Davis et al 2000). These observations suggest that the atrophy of the inner zones is attributable to alterations in the G1/S transition phase of the adrenal cell cycle.…”

“…Conversely, we have observed that the ZG of hypophysectomized rats increases in size and presents larger numbers of BrdU-positive cells. These results are in agreement with those of Nussdorfer et al (1973) and with those of Nickerson and Brownie (1975), whereas other authors have described few or no post-hypophysectomy alterations in the ZG (Deane 1962;Tchen et al 1977;Ceccatelli et al 1995;Davis et al 2000). Nussdorfer et al (1973) have reported that, by post-hypophysectomy day 7, the ZG increases significantly in width, despite absolute decreases in its volume, suggesting that a linear parameter is not a reliable measure of ZG size.…”

Roles of connexins and pannexins in (neuro)endocrine physiology

“…As hypothesized [21], gap junctional communication in the adrenal cortex plays a pivotal role in a number of interactive cell [8,9,13,15] Mouse ? [9,12,14,27] Guinea pig ? [9] Cow ?…”

“…Collectively, this indicates that expression of adrenocortical gap junctions is under hormonal control. Strengthening further the evidence that adrenocortical gap junctions are hormonally regulated, is the finding that hypophysectomy leads to a decrease in Cx43 expression in the ZF and ZR, and that Cx43-mediated cell-cell communication is restored by subsequent ACTH treatment [27]. The physiological contribution of gap junction-mediated cell-cell communication to adrenocortical hormone release is demonstrated by the tissue response to low ACTH concentrations [22,28].…”

Differential expression of VEGF receptors in adrenal atrophy induced by dexamethasone: a protective role of ACTH

“…However, our immunohistochemical analysis of PECAM and von Willebrand-positive cells showed that interactions between steroidogenic cells and endothelial cells in adrenal are largely dictated by proximity. Inside the adrenal cortex, the cells are linked by gap junctions (33) whose expression in the zona fasciculata is restored by ACTH treatment in hypophysectomized mice (10). Thus gap junction-mediated communication between hormone-responsive and nonresponsive cells is one mechanism for a potential paracrine communication.…”