Neuroendocrine circuitry and endometriosis: Progesterone derivative dampens corticotropin-releasing hormone-induced inflammation by peritoneal cells in vitro

Nadja Tariverdian, Mirjam Rücke, J. Szekeres-Barthó, Sandra M. Blois, Eva F. Karpf, Peter Sedlmayr, Burghard F. Klapp, Heribert Kentenich, Friederike Siedentopf, Petra C. Arck

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Clinical symptoms of endometriosis, such as pain and infertility, can be described as persistent stressors. Such continuous exposure to stress may severely affect the equilibrium and bidirectional communication of the endocrine and immune system, hereby further aggravating the progression of endometriosis. In the present study, we aimed to tease apart mediators that are involved in the stress response as well as in the progression of endometriosis. Women undergoing diagnostic laparoscopy due to infertility were recruited (n∈=∈69). Within this cohort, early stage of endometriosis were diagnosed in n∈=∈30 and advanced stage of endometriosis in n∈=∈8. Levels of progesterone in serum were determined. Frequency of progesterone receptor (PR) expression on CD56+ and CD8+ peritoneal lymphocytes was analysed by flow cytometry. The production of tumour necrosis factor (TNF) and interleukin (IL)-10 by peritoneal leukocytes upon stimulation with the potent stress mediator corticotropin-releasing hormone (CRH) and the progesterone derivative dydrogesterone, or both, were evaluated. Furthermore, the production of progesterone-induced blocking factor (PIBF) by peritoneal leukocytes and the expression of PR in endometriotic tissue were investigated. Levels of progesterone in serum were decreased in women with endometriosis and inversely correlated to pain scores. Furthermore, an increased frequency of CD56+PR+ and CD8+PR+ peritoneal lymphocytes was present in advanced endometriosis. The TNF/IL-10 ratio, reflecting cytokine secretion by peritoneal cells, was higher in cells derived from endometriosis patients and could be further heightened by CRH stimulation, whereas stimulation with dydrogesterone abrogated the CRH-mediated inflammation. Finally, the expression of PIBF by peritoneal leukocytes was increased in endometriosis. Low levels of progesterone in the follicular phase could be responsible for the progression of endometriosis and related pain. Peripheral CRH, increasing upon high psychological stress, might contribute to the peritoneal inflammation present in endometriosis. The therapeutic application of progesterone derivatives, CRH blocking agents as well as improvement of stress coping may disrupt the vicious circle between the chronic peritoneal inflammation and high perception of psychological stress in endometriosis.

Original languageEnglish
Pages (from-to)267-278
Number of pages12
JournalJournal of Molecular Medicine
Volume88
Issue number3
DOIs
Publication statusPublished - Mar 2010

Fingerprint

Corticotropin-Releasing Hormone
Endometriosis
Progesterone
Inflammation
Progesterone Receptors
Dydrogesterone
Leukocytes
Psychological Stress
Pain
Interleukin-10
Infertility
In Vitro Techniques
Tumor Necrosis Factor-alpha
Lymphocytes
Endocrine System
Follicular Phase
Serum
Laparoscopy
Immune System
Flow Cytometry

Keywords

  • Endometriosis
  • Pain
  • Peritoneal inflammation
  • PIBF
  • Progesterone
  • Sickness behaviour
  • Steroids
  • Stress

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

Cite this

Neuroendocrine circuitry and endometriosis : Progesterone derivative dampens corticotropin-releasing hormone-induced inflammation by peritoneal cells in vitro. / Tariverdian, Nadja; Rücke, Mirjam; Szekeres-Barthó, J.; Blois, Sandra M.; Karpf, Eva F.; Sedlmayr, Peter; Klapp, Burghard F.; Kentenich, Heribert; Siedentopf, Friederike; Arck, Petra C.

In: Journal of Molecular Medicine, Vol. 88, No. 3, 03.2010, p. 267-278.

Research output: Contribution to journalArticle

Tariverdian, Nadja ; Rücke, Mirjam ; Szekeres-Barthó, J. ; Blois, Sandra M. ; Karpf, Eva F. ; Sedlmayr, Peter ; Klapp, Burghard F. ; Kentenich, Heribert ; Siedentopf, Friederike ; Arck, Petra C. / Neuroendocrine circuitry and endometriosis : Progesterone derivative dampens corticotropin-releasing hormone-induced inflammation by peritoneal cells in vitro. In: Journal of Molecular Medicine. 2010 ; Vol. 88, No. 3. pp. 267-278.
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