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Steroid hormone receptors: activators of gene transcription
1Department of Endocrinology & Reproduction, Erasmus University Rotterdam, The Netherlands.
Abstract:
Over the past three decades, a great deal of evidence has accumulated in favor of the hypothesis that steroid hormones act via regulation of gene expression. The action is mediated by specific nuclear receptor proteins, which belong to a superfamily of ligand-modulated transcription factors that regulate homeostasis, reproduction, development and differentiation. This family includes receptors for steroid hormones, thyroid hormones, hormonal forms of vitamin A and D, peroxisomal activators, and ecdysone. Molecular cloning and structure/function analyses have revealed that all members of the steroid/thyroid hormone/retinoic acid receptor family have a similar functional domain structure: a variable N-terminal region, which is involved in modulation of gene expression; a short well-conserved DNA-binding domain, which is crucial for recognition of specific DNA sequences and for receptor dimerization; and a partially conserved C-terminal ligand-binding domain, which is important for hormone binding and also for receptor dimerization and transactivation. In contrast to other members of the receptor superfamily steroid hormone receptors form transient complexes with several heat shock proteins. This interaction promotes proper folding and stability of the receptor molecule. Hormone binding induces a conformational change in the receptor molecule and simultaneously a dissociation of all heat shock proteins, which results in DNA-binding of the hormone-receptor complex.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Steroid hormones regulate gene expression through nuclear receptor proteins. Hormone binding triggers a conformational change, enabling DNA binding and gene regulation.
Area of Science:
- Molecular Biology
- Endocrinology
- Genetics
Background:
- Steroid hormones are known to regulate gene expression.
- This regulation is mediated by nuclear receptor proteins, part of a larger superfamily of ligand-modulated transcription factors.
- These receptors control essential biological processes like homeostasis, reproduction, and development.
Purpose of the Study:
- To elucidate the mechanism by which steroid hormones regulate gene expression via nuclear receptors.
- To analyze the structure and function of the steroid/thyroid hormone/retinoic acid receptor family.
- To understand the role of heat shock proteins in steroid hormone receptor function.
Main Methods:
- Molecular cloning and analysis of receptor structure and function.
- Investigating the interaction of steroid hormone receptors with heat shock proteins.
- Studying the conformational changes induced by hormone binding.
Main Results:
- All members of the steroid/thyroid hormone/retinoic acid receptor family share a conserved domain structure (N-terminal, DNA-binding, ligand-binding).
- Steroid hormone receptors form transient complexes with heat shock proteins, ensuring proper folding and stability.
- Hormone binding induces a conformational shift, releasing heat shock proteins and facilitating DNA binding of the hormone-receptor complex.
Conclusions:
- Steroid hormone action is fundamentally linked to the regulation of gene expression mediated by nuclear receptors.
- The conserved domain structure of these receptors is critical for their function in DNA binding and transcriptional regulation.
- The interaction with heat shock proteins and the hormone-induced conformational change are key steps in the activation of steroid hormone receptors.