Endocrine Abstracts

Human and animal health has been exposed to endocrine disruptors (EDs) which are chemicals found in pesticides, food or personal care products. The main concern about these disruptors is caused by their interference with the endocrine system causing adverse effects, such as altered reproduction, abnormal neurological development in newborns and children or an elevated susceptibility to hormone-related cancers. The thyroid gland and its hormones belong to major targets that are primarily affected by EDs. Studies on endocrine disrupting effects as well as general endocrine research has been primarily conducted in animal studies due to the lack of representative human models.

The importance of the thyroid gland accentuates its role already during embryonic development and organogenesis by secreting thyroid hormones T3 and T4. It further controls the metabolism of various adult organs, the well-being, and the cardiovascular system. The architecture of the characteristic units of the thyroid gland, the thyroid follicles, is a prerequisite for its functionality. A human thyroid test system is urgently needed to evaluate the effects of new substances on endocrine organs. Therefore, the aim of this study was dedicated to advance the field of in vitro three dimensional (3D) thyroid research using primary human adult thyrocytes. The hypothesis is based on the importance of a 3D environment and the concomitant cell-cell/cell-matrix interactions to mimic in vitro thyroid follicles. In vitro expanded adult thyrocytes, derived from macroscopically normal tissue, were cultured as single 3D culture or in co-culture with endothelial cells (ECs). Adult human thyrocytes dedifferentiated in long-term in vitro culture and lost their transcriptional thyroid-phenotype. The results of 3D cultures, independent from the co-culture with another cell type, demonstrate that the 3D environment exerted a beneficial effect on the transcriptional status of thyrocytes by upregulating thyroid-specific markers. It became obvious that 3D culture approaches without supplying additional extracellular matrix were not sufficient to emulate the native thyroid follicle morphology. A reorganization of thyrocytes was finally induced by the co-culture and the addition of Matrigel^TM. These 3D constructs showed follicular-like structures and are a promising culture strategy for in-vitro test systems of endocrine disruptors. All in all, this study presents for the first time in thyroid research, the successful co-culture of adult human thyrocytes with ECs that induces a reorganization to follicle-like structures in vitro.