Immune aspects and myometrial actions of progesterone and CRH in labor.

Nikolaos Vrachnis,Zoe Iliodromiti,Panayiotis Tsikouras,Stavros Sifakis,Fotodotis M Malamas

doi:10.1155/2012/937618

Abstract

Progesterone and corticotropin-releasing hormone (CRH) have a critical role in pregnancy and labor, as changes related to these hormones are crucial for the transition from myometrial quiescence to contractility. The mechanisms related to their effect differ between humans and other species, thus, despite extensive research, many questions remain to be answered regarding their mediation in human labor. Immune responses to progesterone and CRH are important for labor. Progesterone acts as an immunomodulator which controls many immune actions during pregnancy, and its withdrawal releases the inhibitory action on inflammatory pathways. In humans, a “functional” progesterone withdrawal occurs with onset of labor through changes in progesterone metabolism, progesterone receptors, and other molecules that either facilitate or antagonize progesterone function. Placental CRH acts on the fetal pituitary-adrenal axis to stimulate adrenal production of androgens and cortisol and also acts directly on myometrial cells via its receptors. CRH also affects inflammatory signals and vice versa. Interactions between progesterone and CRH additionally occur during labor. We describe the role of these two hormones in human myometrium and their interactions with the immune system during labor.

Highlights

Mechanical and endocrine mechanisms, immune system responses with inflammatory signals, and release of cytokines, prostaglandins, and oxytocin contribute among others to the transition from myometrial quiescence to labor initiation
In this study we review some of the most recent advances in scientific knowledge concerning progesterone and corticotropinreleasing hormone (CRH) function and interactions in human labor, placing particular focus on the effect on myometrial cells
Inflammatory response involves Tolllike receptors, and progesterone modulates the expression of these receptors in mouse cervix and placenta [45]. Cytokines such as Interleukin 1-β (IL-1β) and TNF-α increase Prostaglandin H Synthase type 2 (PGHS-2) and the synthesis of prostaglandins (PG), while they downregulate prostaglandin 15-hydroxy dehydrogenase (PGDH), the enzyme that converts PGs into inactive metabolites

Summary

Introduction

Mechanical and endocrine mechanisms, immune system responses with inflammatory signals, and release of cytokines, prostaglandins, and oxytocin contribute among others to the transition from myometrial quiescence to labor initiation. The role of these agents has been extensively studied in many animal models, differences exist between species, and these observations do not always apply to humans [1]. Characterization of the human myometrial transcriptome and comprehension of the changes in gene expression during spontaneous labor at term have considerably elucidated the association between spontaneous labor and biological processes such as inflammatory response, chemotaxis, and immune response, as well as molecular functions like cytokine and chemokine activity and chemokine receptor binding. We discuss the immune system responses to these hormones

Progesterone Withdrawal in Labor

Corticotropin-Releasing Hormone Function on Myometrial Contractility

Interactions between Progesterone and CRH in Labor

Conclusion