Abstract
Endometriosis is a chronic inflammatory disorder in which endometrial tissue is found outside the uterine cavity. Previous reports suggest that there is a dysregulation of the hypothalamic pituitary adrenal axis during the progression of endometriosis. Our previous report showed that a short-term treatment with antalarmin, a corticotrophin releasing hormone receptor type 1 (CRHR1) antagonist decreases the number and size of endometriotic vesicles in the auto-transplantation rat model of endometriosis. Our current goal was to examine the mRNA expression of intra-adrenal receptors to better understand the mechanisms of the hypothalamic pituitary adrenal (HPA) axis involvement in endometriosis. We used two groups of female rats. The first received sham surgery or endometriosis surgery before collecting the adrenals after 7 days of the disease progression. The second group of animals received endometriosis surgery and a treatment of either vehicle or antalarmin (20 mg/kg, i.p.) during the first 7 days after endometriosis induction and then the disease was allowed to progress until day 60. Rats with sham surgery served as controls. Results showed that the mRNA expression of the mineralocorticoid (MRC2) receptor was lower in the rats after 7 days of endometriosis surgery and in rats with endometriosis that received antalarmin. In addition, the CRHR1 was significantly elevated in animals that received antalarmin and this was counteracted by a non-significant elevation in CRHR2 mRNA. The glucocorticoid receptor mRNA within the adrenals was not affected by endometriosis or antalarmin treatment. This report is one of the first to explore intra-adrenal mRNA for receptors involved in the HPA axis signaling as well as in the sympatho-adrenal signaling, calling for additional research towards understanding the role of the adrenal glands in chronic inflammatory diseases such as endometriosis.
Highlights
The adrenal glands are triangular shaped organs that sit on top of the kidneys, each composed of an outer cortex and an inner medulla
No significant changes between sham and endo-7 days in mRNA were observed for Glucocorticoid receptors (GR), corticotropin releasing hormone (CRH) receptor type 1 (CRHR1) and CRHR2 (Fig 2C, 2D and 2E)
We examined mineralocorticoid 2 receptor (MCR2), CRHR1 and CRHR2 mRNA within samples of whole adrenal homogenates. mRNA levels of MCR2 showed a significant difference between groups (F(2,32) = 3.53, p
Summary
The adrenal glands are triangular shaped organs that sit on top of the kidneys, each composed of an outer cortex and an inner medulla. ACTH is released into the blood and through binding with the mineralocorticoid 2 receptor (MCR2) mainly in the zona fasciculata of the adrenal cortex, results in the synthesis and secretion of corticosterone and cortisol [2,3]. In addition to GR-mediated ACTH regulation at the level of the pituitary [5], there is evidence supporting an intra-adrenal negative feedback loop where increases in local CORT concentration act to down-regulate the production of more glucocorticoids, via GR located on the adrenal glands [6]. In a mouse model study, it was suggested that the CRH receptor type 1 (CRHR1) in the adrenal cortex is involved in the release of corticosterone, acting separately from the pituitary [8]. CRH receptors have been reported in both the cortex and medulla of human, bovine, canine and rodent adrenal glands [9,10,11,12,13,14,15] alluding to a highly-regulated intra adrenal signaling system
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