The role of progestin receptors in arginine vasopressin cells in the bed nucleus of the stria terminalis and the centromedial amygdala of rats and mice
Abstract (Summary)The vasopressin (AVP)-expressing neurons in the bed nucleus of the stria terminalis (BST) and centromedial amygdala (CMA) are highly sensitive to gonadal hormones. Gonadectomy eliminates, and testosterone replacement restores, AVP immunoreactivity, and AVP mRNA expression in the BST and CMA. Although AVP-ir cells express both androgen and estrogen receptors, the structure of the AVP gene promoter region suggests that these receptors cannot directly influence AVP gene expression. The AVP gene does not contain the consensus sequences for estrogen and androgen receptor response elements. Here the hypothesis that progestin receptors (PR) may be involved in the regulation of AVP expression by gonadal hormones is explored. Results indicate that virtually all AVP-ir cells in the BST and CMA contained PR in rats. Although, neither gonadectomy nor hormonal treatment influenced the expression of PR immunoreactivity in AVP-ir cells, it did significantly reduce the intensity of PR immunoreactivity expressed in AVP-ir cells. The expression of AVP immunoreactivity was examined in male mice that carried a targeted disruption of the PR gene (PRKO). No differences were found in the number of steroid-responsive AVP-ir cells, and the density of AVP-ir fibers between PRKO and wild type mice. This suggests that AVP expression does not critically depend on PR expression. The effect of ZK 98299 on AVP mRNA expression in the BST was studied. Male rats were castrated and implanted with testosterone-filled or empty capsules, or they were sham-operated. Half of the animals in these groups were given daily injections of the PR antagonist ZK 98299 and the other half vehicle for three days. Although castrated rats had fewer AVP mRNA labeled cells than castrated rats that were treated with testosterone or sham-castrated rats, there were no differences in the number of cells that were labeled for AVP mRNA between rats that were treated with ZK 98299 or vehicle. Similarly, castrated rats had less labeling per cell than the other two groups, and again an overall ANOVA did not indicate differences in labeling per cell between rats treated with ZK 98299 or vehicle. However, testosterone-treated and sham-castrated rats that were treated with ZK 98299 had more labeling per cell than their counterparts which were treated with vehicle. These results suggest that if PR influences AVP mRNA expression in the steroid-sensitive AVP cells, it suppresses rather than stimulates AVP mRNA expression.
School Location:USA - Massachusetts
Source Type:Master's Thesis
Date of Publication:01/01/1999