Bio178 Lecture 2 Summer 24 PDF

Lecture 2: The Endocrine System Part 1 BIOL 178  Announcements Quiz 1 PDF has been posted. It’s due Friday by 11:59pm. I will have office hours tomorrow from 11:00am-12:00pm. Discussion 1 is today!...

Lecture 2: The Endocrine System Part 1 BIOL 178  Announcements Quiz 1 PDF has been posted. It’s due Friday by 11:59pm. I will have office hours tomorrow from 11:00am-12:00pm. Discussion 1 is today! 2  Outline of Today’s Lecture 1. Overview of the Endocrine System 2. Peptide Hormones 3. Steroid Hormones 4. The Hypothalamus and the Pituitary a) Posterior pituitary & its hormones b) Anterior pituitary (next lecture!) 3  Learning Objectives By the end of today’s lecture, you should be able to… 1. Describe the major components of the endocrine system. 2. Summarize basic types of effects that hormones can have on cells. 3. Compare and contrast peptide and steroid hormones with respect to structure, storage, synthesis, secretion, transport in blood, receptors, and types of effects. 4. Compare and contrast the anterior and posterior pituitary with respect to structure, hormones secreted, and relationship to the hypothalamus. 4 Lecture 1 Review Question! 5 Lecture 1 Review Question! 6 Overview of the Endocrine System  Types of Chemical Communication Intracrine Chemical mediates intracellular processes Autocrine Cell secretes chemical that affects activity in same cell Paracrine Cell secretes chemical that affects activity in adjacent cells Endocrine Cell secretes chemical that affects activity in distant cells Ectocrine Organism secretes chemical that affects another organism (e.g. pheromones) 8  Definitions: Hormone An organic chemical messenger that… is released from endocrine cells travels through the blood interacts with specific target cells at some distance away, and causes a biological response 9  Definitions: Endocrine Gland A ductless gland from which hormones are released into the bloodstream in response to physiological signals. - Includes tissues not traditionally considered glands (e.g., brain, bone, adipose tissue) Chemical Blood in secretions capillaries Skin surface Hormones are secreted into blood Chemicals produced by the gland Exocrine Gland Endocrine Gland 10  Definitions: Receptor A structure that is on the cell surface or inside a cell and has an affinity for a specific chemical compound. 11  General Features of Hormone Receptors Proteins or glycoproteins Undergo conformational change when bound to hormone Receptor number and affinity are critical determinants of hormone effects Receptor numbers are dynamic 12  Definitions: Target Cell A cell that has specific receptors for, and is physiologically affected by, a particular chemical messenger. Note: one cell may have receptors for many different hormones and/or other chemical signals. 13 Hormone vs. Neurotransmitter vs. Neurohormone Silverthorn 2009 Fig. 6-2 14  Hormonal Effects on Target Cells Hormones do not typically change the function of cells. So what do they do? 1. Change the rate of normal cellular functions - estrogen (E)  oxytocin gene expression - E  electrical activity in brain regions involved in female sexual behavior 15  Hormonal Effects on Target Cells Hormones do not typically change the function of cells. So what do they do? 2. Affect size or morphology of cells - E alters organization of neural synapses in parts of the rodent brain Changes in dendritic spines of hippocampal neurons across the rat estrous cycle (changing E levels) (Hara et al. 2015) 16  Hormonal Effects on Target Cells Hormones do not typically change the function of cells. So what do they do? 3. Affect growth, development, and death of cells - E  number & size of neurons in song-control regions of the avian brain 17  Hormonal Effects on Target Cells Hormones do not typically change the function of cells. So what do they do? 4. Alter sensitivity to other chemical messengers - E  synthesis of cellular receptors for progesterone and some neurotransmitters 18 Classes of Hormones  Classes of Hormones A. Peptides Water-soluble B. Steroids Lipid-soluble C. Amines 1. Catecholamines Water-soluble NE, EPI, dopamine 2. Indoleamines Serotonin, melatonin 3. Thyroid hormones Lipid-soluble Triiodothyronine, tetraiodothyronine 20  Classes of Hormones A. Peptides Water-soluble B. Steroids Lipid-soluble C. Amines 1. Catecholamines Water-soluble NE, EPI, dopamine 2. Indoleamines Serotonin, melatonin 3. Thyroid hormones Lipid-soluble Triiodothyronine, tetraiodothyronine 21 Peptide Hormones  Peptide Hormones: Structure Includes most hormones Amino acid sequence can vary among species – Peptide hormones: ~3-40 amino acids – Polypeptide/protein hormones: ~50-200 amino acids – Glycoproteins: protein + carbohydrate 23  Peptide Hormones: Synthesis & Storage Water-soluble Synthesized as preprohormone Signal peptide is cleaved off N-terminal → prohormone Enzymatic processing of prohormone → ≥1 hormone Hormone (or prohormone + enzyme) is stored in secretory vesicle & eventually expelled from the cell 24  Peptide Hormones: Synthesis & Storage Preprohormone example: PreproTRH (thyrotropin-releasing hormone) Prohormone example: Proinsulin 25  Peptide Hormones: Secretion, Transport, & Metabolism Released in bursts by exocytosis Dissolve in plasma Bind to receptors in a target cell’s membrane Rapidly degraded (by peptidases) or excreted Half-life is around several minutes (short-lived) 26  Peptide Hormones: Receptors Embedded in plasma membrane of target cell Binding of hormone leads to changes inside cell – Modify existing proteins (e.g., membrane channels, metabolic enzymes, transport proteins) = rapid response – May affect synthesis of new proteins = slow response Two major types of receptor complexes: 1. Receptor-enzymes 2. G protein-coupled receptors (GPCRs) 27  Peptide Hormone Receptors 1. Receptor-enzymes -Have intrinsic enzymatic activity -Binding of hormone activates enzyme on cytoplasmic side → series of reactions within cell 28  Peptide Hormone Receptors 2. G protein-coupled receptors (GPCRs) -Act via a G protein and intracellular second messenger (e.g., cAMP) 29  Peptide Hormone Receptors Activation and termination of peptide signaling: 1. Receptor is activated by ligand; hormone has its effect on the cell 2. Receptor is phosphorylated by kinases (inactivation, desensitization) 3. Hormone-receptor complex is endocytosed (internalized) into cell 4. Receptor is recycled or broken down 30  Classes of Hormones A. Peptides Water-soluble B. Steroids Lipid-soluble C. Amines 1. Catecholamines Water-soluble NE, EPI, dopamine 2. Indoleamines Serotonin, melatonin 3. Thyroid hormones Lipid-soluble Triiodothyronine, tetraiodothyronine 31 Steroid Hormones  Steroid Hormones: Structure Three 6-carbon rings & one 21 CH3 conjugated 5-carbon ring 20 C=O 12 18 11 17 16 13 1 19 9 C D 2 14 15 10 8 A B 7 Pregnenolone HO 5 3 4 6 33  Steroid Hormones: Structure Synthesized from cholesterol by tissue-specific enzymes This is why a no-fat or low-fat diet can cause problems Rabbit starvation Synthesized in smooth endoplasmic reticulum Cholesterol present in tissue or taken up from blood Cholesterol → Pregnenolone → Progesterone → Secreted or converted to other steroids 34  Steroid Hormones: Synthesis Silverthorn 2009 35  Steroid Hormones: Sources Steroidogenic tissues: – Adrenal cortex – Testes – Ovaries – Placenta – Nervous system (glial cells and/or neurons) These are the only tissues that are known to synthesize steroids Other tissues may interconvert steroids Tissue-specificity depends on enzymes 36 Steroid Biosynthetic Pathway 37  Steroid Hormones: Secretion Can’t be stored in secretory Serum T Conc. (nmol/L) vesicles! They’ll diffuse out. Synthesis and secretion are coupled Secreted in pulses (bursts) in Time (minutes) response to pulsatile signals T Secretion Rate (nmol/L/min) from pituitary hormones Time (minutes) 38  Steroid Hormones: Transport Not soluble in plasma; circulate in blood bound to carrier proteins/binding proteins (CPs) Thought to be inactive while bound to CPs Free Hormone Hypothesis: Only unbound (free) hormone molecules can enter target cells 39  Steroid Hormones: Metabolism Carrier proteins protect steroids from degradation Inactivated in liver Half-life is about several hours (comparatively long-lived hormones) 40  Steroid Hormones: Entry into Cells How do steroids enter cells? Conventional Model: – Simple diffusion across plasma membranes New Hypothesis: – Facilitated diffusion via transporters – Based on evidence from insects Okamoto et al. 2018 (UCR) 41  Steroid Hormones: “Classical” Actions Bind to receptors in target cell cytoplasm or nucleus Affect gene transcription (slow response) Co-activator proteins may be necessary for transcriptional effects 42  Steroid Hormones: “Classical” Actions Located in cell nucleus or cytoplasm a) Hormone diffuses into cell from blood and… b) Binds to receptor within cell. c) Hormone-receptor (H-R) complex moves to nucleus and… d) Binds to DNA at hormone response element and… e) Stimulates or inhibits gene transcription, leading to… f) Changes in cellular structure or activity 43 Steroid Hormones: “Classical” Actions 44  Steroid Hormones: “Non-Classical” Actions Steroid hormone receptors can also be located in cell membrane. Can be same or different molecule as classical (intracellular) receptor. Steroid-receptor binding can initiate signal-transduction pathways. Leads to rapid (within minutes), non- genomic effects (sometimes including behavior). Can also lead indirectly to genomic effects 45 Steroid Actions: Classical vs. Non-Classical Summary Classical Action Non-Classical Action Steroid hormone Steroid hormone Binds to intracellular receptor Binds to membrane receptor Interacts with genome Increases second messenger & kinase activity Latency of hours Latency of seconds Changes in protein synthesis Cellular response 46  Steroid Hormones: Receptors Some receptors can bind several similar steroids (e.g., androgens, estrogens) Receptors have variable affinity for different steroids depending on the cell type and function Some steroids can bind to several different receptor types Ex: estrogen receptor [ER]: – ERa (intracellular) – ERb (intracellular) – mER (membrane receptor) 47  Classes of Hormones A. Peptides Water-soluble B. Steroids Lipid-soluble C. Amines 1. Catecholamines Water-soluble NE, EPI, dopamine 2. Indoleamines Serotonin, melatonin 3. Thyroid hormones Lipid-soluble Triiodothyronine, tetraiodothyronine 48  Classes of Hormones: Summary Silverthorn 2009, Table 7-1 49 The Hypothalamus & the Pituitary  The Hypothalamus & the Pituitary Hypothalamus – At base of brain; comprises many distinct nuclei – Integrates info from many parts of brain – Important in behavioral drives, emotions, biological rhythms, homeostasis, & endocrine control! Pituitary Gland(s) – Connected to hypothalamus by pituitary stalk (infundibulum) – Anterior and posterior pituitary are developmentally, anatomically, and functionally distinct organs 51  The Hypothalamus & the Pituitary Hormone-secreting regions of the pituitary: Posterior pituitary (also called neurohypophysis or pars nervosa) Anterior pituitary (also called adenohypophysis or pars anterior) Intermediate lobe (also called pars intermedia) 52  Posterior Pituitary (neurohypophysis/pars nervosa) Develops as an outgrowth of the brain Made of brain tissue (neural) Contains axon terminals of neurosecretory cells originating in two nuclei of hypothalamus: – Paraventricular nucleus (PVN) – Supraoptic nucleus (SON) Stores and secretes two peptide hormones synthesized in PVN and SON: – Vasopressin (AVP), or antidiuretic hormone (ADH) – Oxytocin (OT) Nelson 2005 53  Posterior Pituitary 1. Hormone (AVP, OT) is synthesized in cell body of neurosecretory cells (in hypothalamus) and… 2. Is transported down axons into post. pituitary, where it is stored. 3. When neurosecretory cells are stimulated, they conduct action potentials… 4. Causing release of the hormone from the posterior pituitary. 5. Hormone diffuses into capillaries and circulates in the blood. Silverthorn 2009 54  Posterior Pituitary: Hormones Secreted 1. Vasopressin (AVP) = Antidiuretic Hormone (ADH) Acts on kidney to  water retention ( diuresis) Acts on blood vessels to  vasoconstriction Released in response to  blood osmolarity,  blood volume, or  blood pressure Also released within brain to  aggression,  paternal behavior,  social bonding *These functions often vary by species and social situation! 55  Posterior Pituitary: Hormones Secreted 2. Oxytocin (OT) Acts on uterus to trigger smooth muscle contractions which induce/progress labor Acts on breasts to trigger smooth muscle contractions and induce milk letdown Also released within brain to  social bonding,  trust,  empathy,  fear,  maternal behavior 56 Posterior Pituitary: Oxytocin & Uterine Contractions 57 Posterior Pituitary: Oxytocin & Milk Letdown 58 End of Lecture 2 59