HSS 2305 A Lecture 17: Nuclear Receptors

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.

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.