Retinoic Acid Metabolism and Signaling Pathways in the Adult and Developing Mouse Testis

作者：Nadège Vernet, Christine Dennefeld, Cécile Rochette‐Egly, Mustapha Oulad‐Abdelghani, Pierre Chambon, Norbert B. Ghyselinck, Manuel Mark · 发表于：Endocrinology · 年份：2005 · DOI：10.1210/en.2005-0953 · 被引用次数：264 · 研究领域：Retinoids in leukemia and cellular processes、Estrogen and related hormone effects、Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

As a first step in investigating the role of retinoic acid (RA) in mouse testis, we analyzed the distribution pattern of the enzymes involved in vitamin A storage (lecithin:retinol acyltransferase), RA synthesis (beta-carotene 15,15'-monoxygenase and retinaldehyde dehydrogenases) and RA degradation (cytochrome P450 hydroxylases) as well as those of all isotypes of receptors transducing the RA signal [RA receptors (RARs) and rexinoid receptors (RXRs)]. Our data indicate that in adult testis 1) cytochrome P450 hydroxylase enzymes may generate in peritubular myoid cells a catabolic barrier that prevents circulating RA and RA synthesized by Leydig cells to enter the seminiferous epithelium; 2) the compartmentalization of RA synthesis within this epithelium may modulate, through paracrine mechanisms, the coupling between spermatogonia proliferation and spermatogenesis; 3) retinyl esters synthesized in round spermatids by lecithin:retinol acyltransferase may be transferred and stored in Sertoli cells, in the form of adipose differentiation-related protein-coated lipid droplets. We also show that RARalpha and RXRbeta are confined to Sertoli cells, whereas RARgamma is expressed in spermatogonia and RARbeta, RXRalpha, and RXRgamma are colocalized in step 7-8 spermatids. Correlating these expression patterns with the pathological phenotypes generated in response to RAR and RXR mutations and to postnatal vitamin A deficiency suggests that spermiation requires RXRbeta/RARalpha heterodime...