HSS 2305 A Lecture 17: Nuclear Receptors

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Questions and Answers

Which statement accurately describes the type of receptors that bind steroid hormones?

They are membrane-bound receptors that transmit signals into the cytoplasm.

They adhere to the cell membrane and require transport proteins to function.

They are cytoplasmic receptors that bind to lipid-soluble signaling molecules. (correct)

They only function in the presence of external signaling molecules.

What is a defining characteristic of nuclear receptors compared to cell surface receptors?

Nuclear receptors are soluble cytosolic proteins. (correct)

Nuclear receptors can only function in the presence of nuclear membrane.

Nuclear receptors only bind to polar molecules.

Nuclear receptors require transmembrane domains to function.

Which of the following is not included in the examples of ligands for nuclear receptors?

Leukotrienes (correct)

Certain vitamins

Thyroid hormones

Steroid hormones

How many nuclear receptors have been described with known ligands in humans?

24 Signup and view all the answers

What distinguishes orphan receptors from the known nuclear receptors?

Orphan receptors have no known ligands. Signup and view all the answers

What is the primary function of nuclear receptors?

To bind to DNA and regulate gene expression. Signup and view all the answers

Which of the following describes NR-ligands?

Lipophilic molecules that diffuse across cell membranes. Signup and view all the answers

Which type of nuclear receptor is predominantly associated with steroid hormones?

Monomer type nuclear receptors. Signup and view all the answers

What distinguishes homodimer nuclear receptors from heterodimer nuclear receptors?

Homodimer receptors consist of two identical nuclear receptors. Signup and view all the answers

What is the primary characteristic of the nuclear receptor family?

They are classified based on mechanisms or sequence homology. Signup and view all the answers

What is the primary role of the zinc finger domains within the DNA-binding domain (DBD)?

To bind to specific genes known as Hormone Response Elements (HRE) Signup and view all the answers

Which domain influences intracellular trafficking and connects the DBD with the LBD?

Hinge region Signup and view all the answers

Which feature of the Ligand Binding Domain (LBD) is described as being highly conserved in structure yet moderately conserved in sequence?

The anti-parallel alpha helices arrangement Signup and view all the answers

What is the function of the N-terminal domain (A/B) in the Retinoic Acid Receptor?

It serves as a transcriptional Activation Function Signup and view all the answers

Which of the following statements accurately describes the high degree of conservation in the Retinoic Acid Receptor (RAR) family?

Differences in the LBD facilitate design of receptor-specific ligands Signup and view all the answers

Study Notes

Course HSS 2305 A: Molecular Mechanisms of Disease

This course covers molecular mechanisms of disease
Lecture 17 focuses on nuclear receptors and endocrinology

Lecture 17: Nuclear Receptors and Endocrinology

Professor Ajoy Basak, Ph.D.
Professor's Contact Information (Title, Department, Address, Phone, Email, Website) is provided
Topics include introduction to molecular biology, diseases, biological molecules, cells, organelles, bioenergetics, proteins, enzymes, mitochondria, cell membrane, cell-environment interactions, genes, transcription, translation and more
Detailed lecture topics, dates, and times are provided for the fall 2024 semester, covering 23 lectures, including specific reading materials.
Quizzes, tests, and examinations dates and times are specified throughout the semester. Includes lectures on Post Translational Protein Modification/Types/Disease implications, DNA Replication, DNA Damage, and DNA Repair
A significant portion of the lecture covers Nuclear Receptors
Details about Intracellular Receptors and Endocrine Systems
Two main types of intracellular receptors are discussed: cytoplasmic and nuclear receptors
Intracellular receptors bind extracellular signaling molecules that can penetrate cell membranes, or are transported across these membranes
Key intracellular receptors are lipid soluble
These receptors are specifically used by steroid hormones, such as cortisol, estrogens, androgens
The hormone-receptor complex binds parts of DNA called "Hormone Responsive Elements" leading to alteration of gene expression
Nuclear receptors (NR) are different from cell-surface receptors
Nuclear receptors are soluble cytosolic proteins that function as receptors and bind to specific ligands in animals (Steroids; Thyroids; Vitamin A, D, etc) which are not found in plants, algae, fungi
NR numbers in humans (48) and C-elegans (270) are discussed.
NR binding to DNA and regulating gene expression is stressed
The effects of ligand binding, causing up and down regulation of gene expression are pointed out
NR molecules (Ligands) are mostly steroids, thyroid hormones and vitamins.
Specific steroid hormones (sex hormones like estrogens, androgens, progestogens; and non-sex steroid hormones like glucocorticoids, mineralocorticoids) are provided
The details of Non-steroid hormones, which are also NR ligands (Retinoic Acid, Triiodothyronine) are noted
Different types of nuclear receptors (monomer; hetero- or homo-dimer) are discussed.
Examples include PPAR heterodimerizes with Retenoid X Receptor(RXR).
Thiazolidinediones (a diabetes medication) are mentioned.
Nuclear Receptor Family, with their domains including DNA Binding Domain and Ligand Binding Domain
Classification of Nuclear Receptors based on mechanism or sequence homology.
Various types of receptors are discussed, including their ligand-specific functions.

Heat Shock Proteins (HSPs) as Co-receptors

HSPs act as chaperones that support the proper folding of other proteins
HSP levels increase in response to stress such as temperature change
They stabilize other proteins.
The role of HSPs in gene expression is highlighted, with implications in cancer treatment

Translocation of GR into the Nucleus

Describes the process and the proteins involved in the process of translocation (Hsp90, Immunophilins, FKBP51/52, Dynein)

Releasing Hormones and Their Function

Describes releasing hormones, including peptides hormones (LH, ACTH, FSH) and steroid hormones (progesterone, testosterone, cortisol, estradiol).
Details about the origin and function of these hormones, including their role in regulating other hormone release in the pituitary gland.

Biological Roles of Nuclear Receptors and Disease Implications

Discusses the roles of nuclear receptors in different biological processes (homeostasis, embryonic development, liver function) and their involvement in diseases.
Diseases associated with mutations in nuclear receptors, e.g., mutations in the androgen receptor causing infertility or prostate cancer, mutations in PPAR leading to type II diabetes or colon cancer and mutations in the estrogen receptor causing breast cancer are highlighted.

Cell surface Receptors and Nuclear Receptors - Comparison

A comparison chart details different pathways of signaling
Protein and peptide hormones tend to use cell-surface receptors
Steroid hormones tend to use intracellular receptors
Key differences are discussed

Endocrine System

Discusses a group of specialized organs and body tissues
The Hypothalamus, Pituitary, Thyroid, Parathyroid, Pancreatic Islets, Adrenal Glands, Testes(males), Ovaries(female), Mammary glands, adipose tissue and Placenta are major glands and organs
The role of the hypothalamus-pituitary-adrenal (HPA) axis in regulating stress response, digestion, immune system and more is explored.
Key hormones are described
Hormone types: (steroids, proteins, peptides, and modified amino acids)
Detailed explanation of hormone function and action during hormone release
Control of hormonal balance and diseases that arise from imbalance

Hypothalamic-Pituitary Hormone-Gland Loops

Hormone loops between Hypothalamus, Anterior Pituitary, and other organs/Glands
Details on Growth Hormone, Prolactin, Thyroid Stimulating Hormone (TSH), Adrenocorticotrophic Hormone (ACTH), Follicle Stimulating Hormone (FSH), and Luteinizing Hormone (LH).

Hormonal Balance

The importance of maintaining a precise level of hormone is emphasized.
Imbalances lead to diseases or dysfunction.

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Description

Dive into Lecture 17 of HSS 2305 A, where we explore the intricate roles of nuclear receptors in endocrinology. This lecture highlights crucial molecular mechanisms associated with various diseases. Join Professor Ajoy Basak, Ph.D., as he guides you through the foundations of molecular biology and disease pathology.