biology

Progesterone receptor

Progesterone receptor is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Progesterone receptor rather than just read about it. In short: The progesterone receptor (PR), also known as NR3C3 or nuclear receptor subfamily 3, group C, member 3, is a protein found inside cells. It is activated by the steroid hormone progesterone.

Key takeaways

Progesterone receptor belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Progesterone receptor to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Progesterone receptor from memory before moving on to harder problems.

Reference excerpt

The progesterone receptor (PR), also known as NR3C3 or nuclear receptor subfamily 3, group C, member 3, is a protein found inside cells. It is activated by the steroid hormone progesterone. In humans, PR is encoded by a single PGR gene residing on chromosome 11q22, it has three isoforms: PR-A, PR-B, and PR-C. Though PR-A and PR-B are much more well studied compared to PR-C. The PR-B is the positive regulator of the effects of progesterone, while PR-A serve to antagonize the effects of PR-B.

Mechanism Progesterone is necessary to induce activation of the progesterone receptors. When no binding hormone is present the carboxyl terminal inhibits transcription. Binding to a hormone induces a structural change that removes the inhibitory action. Progesterone antagonists prevent the structural reconfiguration. After progesterone binds to the receptor, restructuring with dimerization follows and the complex enters the nucleus and binds to DNA. There transcription takes place, resulting in formation of messenger RNA that is translated by ribosomes to produce specific proteins.

Structure

In common with other steroid receptors, the progesterone receptor has a N-terminal regulatory domain, a DNA binding domain, a hinge section, and a C-terminal ligand binding domain. A special transcription activation function (TAF), called TAF3, is present in the progesterone receptor-B, in a B-upstream segment (BUS) at the amino acid terminal. This segment is not present in the receptor-A.

Isoforms

The single-copy human (hPR) gene uses separate promoters and translational start sites to produce three isoforms, PR-A, -B, and -C. PR-A and -B are identical except for an additional 165 amino acids present only in the N terminus of PR-B. PR-C is even smaller, starting at the 595th amino acid of PR-B. Although the three isoforms share many important structural domains, they are functionally distinct. PR-A and PR-B are disticnt transcription factors, which mediate their own response genes and physiological effects with little overlap. PR-C being the smallest, does not have the important AF1, AF3, or DNA-binding domains. Thus, PR-C is not a transcription factor. However, PR-C can dimerize, participate in nuclear translocation, and modulate the actions of PR-A and PR-B. Selective ablation of PR-A in a mouse model, resulting in exclusive production of PR-B, unexpectedly revealed that PR-B contributes to, rather than inhibits, epithelial cell proliferation both in response to estrogen alone and in the presence of progesterone and estrogen. These results suggest that in the uterus, the PR-A isoform is necessary to oppose estrogen-induced proliferation as well as PR-B-dependent proliferation.

Functional polymorphisms Six variable sites, including four polymorphisms and five common haplotypes have been identified in the human PR gene . One promoter region polymorphism, +331G/A, creates a unique transcription start site. Biochemical assays showed that the +331G/A polymorphism increases transcription of the PR gene, favoring production of hPR-B in an Ishikawa endometrial cancer cell line. Several studies have now shown no association between progesterone receptor gene +331G/A polymorphisms and breast or endometrial cancers. However, these follow-up studies lacked the sample size and statistical power to make any definitive conclusions, due to the rarity of the +331A SNP. It is currently unknown which if any polymorphisms in this receptor are of significance to cancer. A study of 21 non-European populations identified two markers within the PROGINS haplotype of the PR gene as positively correlated with ovarian and breast cancer.

Animal studies

Development Knockout mice of the PR have been found to have severely impaired lobuloalveolar development of the mammary glands as well as delayed but otherwise normal mammary ductal development at puberty.

Behavior During rodent perinatal life, progesterone receptor (PR) is known to be transiently expressed in both the ventral tegmental area (VTA) and the medial prefrontal cortex (mPFC) of the mesocortical dopaminergic pathway. PR activity during this time period impacts the development of dopaminergic innervation of the mPFC from the VTA. If PR activity is altered, a change in dopaminergic innervation of the mPFC is seen and tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine synthesis, in the VTA will also be impacted. TH expression in this area is an indicator of dopaminergic activity, which is believed to be involved in normal and critical development of complex cognitive behaviors that are mediated by the mesocortical dopaminergic pathway, such as working memory, attention, behavioral inhibition, and cognitive flexibility. Research has shown that when a PR antagonist, such as RU486 (also known as mifepristone), is administered to rats during the neonatal period, decreased tyrosine hydroxylase immunoreactive (TH-ir) cells density, a strong co-expresser with PR-immunoreactivity (PR-ir), is seen in the mPFC of juvenile rodents. Later on, in adulthood, decreased levels of TH-ir in the VTA are also shown. This alteration in TH-ir fiber expression, an indicator of altered dopaminergic activity resulting from neonatal PR antagonist administration, has been shown to impair later performance on tasks that measure behavioral inhibition and impulsivity, as well as cognitive flexibility in adulthood. Similar cognitive flexibility impairments were also seen in PR knockout mice as a result of reduced dopaminergic activity in the VTA. Conversely, when a PR agonist, such as 17α-hydroxyprogesterone caproate, is administered to rodents during perinatal life, as the mesocortical dopaminergic pathway is developing, dopaminergic innervation of the mPFC increases. As a result, TH-ir fiber density also increases. Interestingly, this increase in TH-ir fibers and dopaminergic activity is also linked to impaired cognitive flexibility with increased perseveration later on in life. In combination, these findings suggest that PR expression during early development impact later cognitive functioning in rodents. Furthermore, it appears as though abnormal levels of PR activity during this critical period of mesocortical dopaminergic pathway development may have profound effects on specific behavioral neural circuits involved in the formation of later complex cognitive behavior.

Ligands

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with Progesterone receptor

Start with the simplest possible case. Write down what Progesterone receptor claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Progesterone receptor before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Progesterone receptor ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Progesterone receptor

In research: Progesterone receptor appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Progesterone receptor in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Progesterone receptor is common in secondary-school and first-year university syllabi. It links to neighbouring topics Genes on human chromosome 11, Intracellular receptors, Progestogens, so understanding it makes those chapters shorter.
In everyday life: Look for Progesterone receptor outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Progesterone receptor in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Progesterone receptor means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Progesterone receptor out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Progesterone receptor in simple terms?

The progesterone receptor (PR), also known as NR3C3 or nuclear receptor subfamily 3, group C, member 3, is a protein found inside cells. It is activated by the steroid hormone progesterone.

Why does Progesterone receptor matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Progesterone receptor?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Progesterone receptor.