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Related Concept Videos

Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
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Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
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G-protein Coupled Receptors01:21

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G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
G-protein Coupled Receptors01:21

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G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.

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Related Experiment Video

Updated: May 18, 2026

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
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Published on: December 19, 2018

Canid progesterone receptors lack activation function 3 domain-dependent activity.

Ana Gracanin1, Monique E van Wolferen, Carol A Sartorius

  • 1Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, 3584 CM Utrecht, The Netherlands.

Endocrinology
|October 9, 2012
PubMed
Summary

Canine progesterone receptor B (cPR-B) has weak transactivation due to mutations, unlike other species. This finding questions PR-B

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A Modified Co-Culture System for Understanding Granulosa-Theca Cell Interactions in the Bovine Ovary

Published on: September 19, 2025

Area of Science:

  • Reproductive biology
  • Endocrinology
  • Molecular genetics

Background:

  • Progesterone receptors (PRs), specifically PR-B and PR-A, regulate female reproductive functions.
  • PR-B is essential for mammary gland development and is a stronger transactivator than PR-A due to its activation function 3 (AF3) domain.
  • Dogs exhibit high sensitivity to progesterone-induced mammary cancer, prompting investigation into canine PR-B function.

Purpose of the Study:

  • To investigate the functional differences of canine PR-B (cPR-B) compared to other species.
  • To determine the impact of mutations within the AF3 domain on cPR-B transactivation potential.
  • To explore the implications of cPR-B function on mammary gland development and cancer in canids.

Main Methods:

  • Comparative analysis of PR-B sequences and functional domains across species.
  • Transient transfection assays using progesterone-responsive reporter genes in various cell lines.
  • Stable transfection of doxycycline-inducible cPR-B in canine mammary cells to assess target gene activation.
  • Functional restoration of cPR-B by replacing the canine AF3 domain with the human counterpart.

Main Results:

  • Canine PR-B (cPR-B) exhibits significantly weaker transactivation potential compared to human PR-B.
  • Mutations within the AF3 core sequence motifs and lack of N-terminal modifications contribute to cPR-B's reduced activity.
  • Replacing the canine AF3 domain with the human version restored cPR-B function to human PR-B levels.
  • The impaired AF3-dependent transcriptional activity was specific to canids (dog, wolf, fox, raccoon dog) and absent in other caniform species.

Conclusions:

  • Canine PR-B possesses limited transcriptional activity due to unique AF3 domain mutations, distinguishing it from other species.
  • Despite weak transactivation, canids develop normal mammary glands and are prone to mammary tumors, challenging the established role of PR-B in cancer.
  • These findings may elucidate unique aspects of canid reproduction and mammary cancer susceptibility.