Expression of Steroid Receptors in Ameloblasts during Amelogenesis in Rat Incisors.

Sophia Houari,Katia Jedeon,Ariane Berdal,Sophia Loiodice,Sylvie Babajko

doi:10.3389/fphys.2016.00503

Abstract

Endocrine disrupting chemicals (EDCs) play a part in the modern burst of diseases and interfere with the steroid hormone axis. Bisphenol A (BPA), one of the most active and widely used EDCs, affects ameloblast functions, leading to an enamel hypomineralization pattern similar to that of Molar Incisor Hypomineralization (MIH). In order to explore the molecular pathways stimulated by BPA during amelogenesis, we thoroughly investigated the receptors known to directly or indirectly mediate the effects of BPA. The expression patterns of high affinity BPA receptors (ERRγ, GPR30), of ketosteroid receptors (ERs, AR, PGR, GR, MR), of the retinoid receptor RXRα, and PPARγ were established using RT-qPCR analysis of RNAs extracted from microdissected enamel organ of adult rats. Their expression was dependent on the stage of ameloblast differentiation, except that of ERβ and PPARγ which remained undetectable. An additional large scale microarray analysis revealed three main groups of receptors according to their level of expression in maturation-stage ameloblasts. The expression level of RXRα was the highest, similar to the vitamin D receptor (VDR), whereas the others were 13 to 612-fold lower, with AR and GR being intermediate. Immunofluorescent analysis of VDR, ERα and AR confirmed their presence mainly in maturation- stage ameloblasts. These data provide further evidence that ameloblasts express a specific combination of hormonal receptors depending on their developmental stage. This study represents the first step toward understanding dental endocrinology as well as some of the effects of EDCs on the pathophysiology of amelogenesis.

Highlights

The environment has become increasingly contaminated by various pollutants which may have a role in the modern burst of diseases
The effects of vitamin D (VD) on bone and enamel mineralization are well-known, but little is known about all other endocrine regulations of dental growth and mineralization
Recent reports showing the effects of Endocrine disrupting chemicals (EDCs) on enamel mineralization (Bloch-Zupan et al, 1994; Alaluusua et al, 2004; Jan et al, 2007; Jedeon et al, 2014b) suggest that amelogenesis may be regulated by endogenous steroid hormones

Summary

Introduction

The environment has become increasingly contaminated by various pollutants which may have a role in the modern burst of diseases. Among environmental toxicants, endocrinedisrupting chemicals (EDCs) have been associated over these past 50 years with many existing or emerging diseases including hormone-dependent cancers, diabetes, obesity, and decreased fertility (De Coster and van Larebeke, 2012; Maqbool et al, 2016). This enamel disease presents a similar epidemiological evolution to EDCrelated diseases It was almost non-existent before the 80s’, but affects ∼15–18% of 6 to 9-year-old children (Jälevik, 2010; Jedeon et al, 2015). The mechanism of action of BPA in dental cells is even less evident as its putative receptors are poorly defined in dental tissues, except for ERα (Jedeon et al, 2014a)

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