How do steroid hormones bind to receptor proteins in the cytoplasm of the target cell, and what is the role of the receptor-hormone complex in gene transcription?

Sourav PanNovember 9, 2024

Answered

Steroid hormones play a crucial role in regulating various physiological processes by binding to specific receptor proteins in the cytoplasm of target cells. This interaction initiates a cascade of events that ultimately leads to changes in gene transcription. Here’s a detailed overview of how this process occurs and the role of the receptor-hormone complex in gene transcription.

Binding of Steroid Hormones to Receptor Proteins

1. Diffusion into the Cell:
   • Steroid hormones, being lipophilic (fat-soluble), can easily diffuse through the plasma membrane of target cells. Once inside, they encounter specific receptor proteins located in the cytoplasm or nucleus.
2. Receptor Binding:
   • Upon entering the cell, steroid hormones bind to their corresponding intracellular receptors. These receptors are usually found in an inactive form bound to heat shock proteins (HSPs) like Hsp90, which help stabilize them in the cytoplasm. The binding of the hormone causes a conformational change in the receptor, leading to the dissociation of HSPs and activation of the receptor .
3. Translocation to the Nucleus:
   • After activation, the receptor-hormone complex translocates into the nucleus. This movement is facilitated by nuclear localization signals (NLS) present within the receptor structure, allowing it to pass through the nuclear envelope .

Role of the Receptor-Hormone Complex in Gene Transcription

1. Dimerization:
   • In many cases, steroid hormone receptors function as dimers (either homodimers or heterodimers). Upon binding with their respective hormones, these complexes often dimerize, which is essential for their subsequent interaction with DNA .
2. Binding to Hormone Response Elements (HREs):
   • The activated receptor-hormone complex binds to specific DNA sequences known as hormone response elements (HREs) located in the promoter regions of target genes. This interaction is crucial for regulating gene expression.
3. Transcriptional Activation:
   • Once bound to HREs, the receptor-hormone complex recruits various coactivators and transcription factors that facilitate transcription initiation. These interactions can stabilize general transcription factors at the TATA box or promote interactions with other proteins bound to upstream promoter sequences . This recruitment enhances RNA polymerase’s ability to initiate transcription of messenger RNA (mRNA), leading to protein synthesis.
4. Gene Expression Modulation:
   • The receptor-hormone complex not only activates gene transcription but can also repress it by recruiting corepressors that inhibit transcriptional activity. This dual capability allows for fine-tuned regulation of gene expression depending on cellular context and hormonal signals .
5. Long-Term Effects:
   • The effects of steroid hormones on gene transcription typically manifest over a longer time frame (hours to days), as they involve changes in protein synthesis and cellular function.