The hamster androgen receptor promoter: a molecular analysis

The steroid/thyroid hormone receptors are members of a very large family of nuclear-activated transcription factors. These receptors play a crucial role in most biological function, including regulation of development, metabolism, behaviour and reproduction. Among androgen receptor (AR), we have recently demonstrated that its expression in the Harderian gland (HG) of the male hamster is under a well-co-ordinated cross-talk between various steroid hormone receptors. Here, are presented data on the sequence of hamster AR promoter region (5'UTR) and the molecular tools of its regulation. The 5'UTR is 1585 bp. The promoter region shows various responsive elements. Two putative CREM elements are present at -71 and -1576 bp. A putative retinoic acid responsive element is present at -1476 bp. An androgen/glucocorticoid responsive element is present at -473 bp. A putative thyroid hormone-responsive element at -381 bp and an estrogen responsive element at -230 bp. Also, a homopurinic stretch is evident between -1199 and -1118. Furthermore, Sp1 sites are also spread along the sequence. As well as for human, mouse, rat and pig, the hamster lacks the canonical promoter TATA and CCAAT boxes. Gel retardation experiments confirm the presence of active responsive elements for AR, estrogen receptor, glucocorticoid receptor and thyroid hormone receptor. Previous data on the regulation of expression of AR by other members of steroid/thyroid hormone receptors well correlate with sequence analysis and gel retardation experiments. Thus, androgens, thyroid hormone, stimulate the AR transcription, while synthetic glucocorticoid (Dex) and estrogen are potent inhibitors of AR expression. The comparison of hamster AR promoter sequence with other AR promoter shows an 89, 82, 84 and 84% identity with human, rat, mouse and pig AR promoter, respectively. These results, in the light of the extreme plasticity of hamster HG, suggest that the comparative study of expression and regulation of AR gene in the HG of the hamster offers a useful tool to approach the normal and pathological phenotype in human.