Regulation of Endothelial Permeability in the Corpus Luteum: A Review of the Literature

Abstract

The development of the human corpus luteum (yellow body) is dictated by a strictly controlled system of mutually communicating cells, the luteal steroid hormone-producing cells and endothelial cells. This cell-to-cell communication facilitates control of neoangiogenesis which is a prerequisite for the development of the corpus luteum and its function, the rapid release of large amounts of progesterone into the blood-vascular system. Preconditions for this process are the hormonal regulation of endothelial cell proliferation as well as of vascular permeability through LH and hCG. The morphological correlates of endothelial permeability are cell-to-cell adhesion molecules such as adherens junctions (AJ) and tight junctions (TJ) that open and close the gaps between mutually interacting, neighbouring endothelial cells like a “zip fastener”. Various types of cell adhesion molecules have been detected in the corpus luteum such as occludin, claudin 1 and claudin 5 as well as VE-cadherin. It may be assumed that the regulation of AJ and TJ proteins is of particular importance for the permeability and thus for the function of the corpus luteum in early pregnancy since hCG treatment leads to a down-regulation of cell adhesion molecules in the luteal vessels. This effect is apparently mediated by VEGF. From a functional point of view, the hCG-dependent and VEGF-mediated down-regulation of cell adhesion molecules leads to a reduced transmissibility of cell-to-cell contacts and thus to an increased endothelial permeability. In this process the various cell adhesion molecules are not only directly regulated by VEGF but they also mutually interact and thus influence one another.

Zusammenfassung

Die Entwicklung des humanen Corpus luteum ist durch ein streng reguliertes System von miteinander kommunizierenden Zellen, den lutealen Steroidhormon-produzierenden Zellen und den Endothelzellen, geprägt. Diese Zell-Zell-Kommunikation ermöglicht die Kontrolle von Neoangiogenese, die für die Entstehung des Corpus luteum Voraussetzung ist, und deren Aufgabe die rasche Freigabe von großen Mengen Progesteron ins Blutgefäßsystem ist. Voraussetzung für diesen Vorgang ist die hormonelle Regulation der Endothelzellproliferation sowie der Gefäßpermeabilität durch LH und hCG. Das morphologische Korrelat der endothelialen Permeabilität sind Zell-Zell-Adhäsionsmoleküle wie Adherens Junctions (AJ) und Tight Junctions (TJ), die „reißverschlussartig“ den Spalt benachbarter interagierender Endothelzellen öffnen und schließen. Im Corpus luteum konnten verschiedene Zell-Adhäsionsmoleküle nachgewiesen werden, darunter Occludin, Claudin 1 und Claudin 5 sowie VE-Cadherin. Es ist davon auszugehen, dass die Regulation von AJ- und TJ-Proteinen von besonderer Bedeutung für die Permeabilität und damit die Funktionalität des Corpus luteum in der Frühschwangerschaft ist, da hCG-Behandlung zu einer Herunterregulation der Zell-Adhäsionsmoleküle in den Lutealgefäßen führt. Offensichtlich ist dieser Effekt VEGF-vermittelt. Funktionell betrachtet führt die hCG-abhängige und VEGF-vermittelte Herunterregulation von Zelladhäsionsmolekülen zu einer verminderten Durchlässigkeit der Zell-Zell-Kontakte und damit zu gesteigerter endothelialer Permeabilität. Dabei werden die verschiedenen Zell-Adhäsionsmoleküle nicht nur direkt durch VEGF reguliert, sondern sie interagieren auch untereinander und beeinflussen sich auf diese Weise gegenseitig.

Key words

permeability - tight junction - adherens junction - corpus luteum - hCG

Schlüsselwörter

Permeabilität - Tight Junction - Adherens Junction - Corpus luteum - hCG

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