ABSTRACT

Downregulation of hormone receptors by their ligands is a classical concept in endocrinology. This is generally true of tissues of adult organisms or differentiated or transformed cell lines. However, almost 20 years ago in studies on regulation of egg protein genes by steroid hormones a substantial and rapid upregulation of the receptor by its own ligand was found to precede the activation of its target genes. More examples of autoinduction of steroid/thyroid hormone/retinoid family of nuclear receptors have emerged recently, in which the hormone or another signal regulates some process of postembryonic development or induces a specific set of genes. This phenomenon  will be illustrated in the review/minireview by work from the authors’ laboratory on estrogen and thyroid hormone receptors during amphibian egg protein gene expression and metamorphosis, respectively. In discussing the general significance of nuclear receptor upregulation a dual receptor level hypothesis will be presented according to which receptor autoinduction may be a pre-requisite for the initiation of the downstream gene activation cascade.