Agenda Introduction & Syllabus (always exciting!) Chapter 18: Endocrine System Lab 33 Looking ahead-wed: Chapter 18 Homeostasis Homeostasis refers to a state of relative balance within the body, and the process by which it is maintained The endocrine system plays an enormously important role in maintaining homeostasis Primarily via hormone release and feedback mechanisms Homeostasis In negative feedback a stimulus causes a response which works to reduce the stimulus stabilizing In positive feedback a stimulus causes a response which further increases the stimulus Preserving homeostasis requires long term co-ordination of cell activity throughout the body Nervous system versus Endocrine system NS: monitors specific cells or groups of cells, with responses that are short in duration Endocrine system 1
General Characteristics of the Endocrine System Chemicals released by cells enter the bloodstream Target specific cells/organs Regulated by negative feedback Goal is to preserve homeostasis How do cells communicate? Direct Communication-(specialized and vary rare) ie. Mediates contraction of cardiac cells Cell 1Cell 2 Indirect Communication- most cellular communication, involves release and receipt of chemical messenger Cell 1 Cell 2 Two Types of Indirect Communication 1. Paracrine= communication from cell to cell within a single tissue -Messenger is released in bloodstream, but typically effects are local Cell 1 Cell 2 2. Endocrine= hormones released from one cell acting at distant tissue(s) Cell 1 Cell 2 bloodstream Let s pause and review Most cellular communication, involves release and receipt of chemical messenger How does release occur? What s involved? How does receipt occur? What s involved? Chemical messengers? Nervous system examples anyone? Cell 1 Cell 2 2
In the Nervous System We saw that the NS is in charge of regulating split second situations Response is fast! Synapse, not bloodstream!! Many receptors we encountered were ion channels (but not all) When activated, do ion channels a cause a quick change in the receiving cell, or a slow change? Why? In the Endocrine System One hormone may have effects on more than one cell type (think receptors!) Effects may have fast or slow onset with short or long duration (from seconds up to days or longer) One cell can respond to numerous different hormones (think receptors again!) Thus, endocrine system well suited for regulating gradual and coordinated processes One hormone may have effects on more than one cell type One cell can respond to numerous different hormones Endocrine System Effects may have fast or slow onset with short or long duration Maybe stimulation of this receptor activates an enzyme Maybe stimulation of this receptor affects transcription of that same enzyme 3
Two types of glands in the body Exocrine glands -secrete products through a duct, ie: sweat, oil, salivary glands Endocrine glands -release hormones into the blood or lymph ie: pituitary, pancreas, thyroid Hormones = chemicals secreted by cells into extracellular fluid that regulate metabolic functions of other cells (tissues) in the body Note that some organs have a solely endocrine function, while other organs have endocrine function as an additional function, in addition to others, ie pancreas Hormones are classified based on their chemical structure 1. Amino acid derived Three Classes of Hormones 1. Amino acid derived Thyroid hormones Or Epi, or NE, DA 2. Peptide derived 3. Lipid derived 2. Peptide derived -Two groups 3. Lipid derived -Two groups AA 1 AA 3 AA 3 AA 4 Cholesterol 4
Peptide Derived Hormones Glycoproteins 200 AA long, with sugar moieties TSH, LH, FSH Small/Large diverse group From 9 AA to small proteins ADH, oxytocin (short) GH, PRL, etc Don t focus on these differences, just appreciate that these hormones are chains of amino acids encoded for by genes! These do not come about by way of the diet, but by way of the nucleus and the ribosome! Lipid Derived Hormones 1. Eicosanoids (from arachadonic acid) -Membrane lipids function as signaling molecule precursors! Wow, weird! 2. Steroids (from cholesterol) - released from reproductive organs, adrenal glands (corticosteroids) and kidneys (calcitriol) Phospholipid bilayer A flow chart of hormones Another flow chart of hormones 5
The final flow chart of hormones Let s get back to the interesting stuff So, there are lots of different types of hormones, great. WHAT DO THEY DO AFTER THEY BIND A TARGET CELL? And, how do they do it? This is a short, and intentionally ambiguous list of what hormones may do at a target cell 1. Stimulate synthesis of an enzyme or structural protein 2. Increase or decrease the rate of synthesis of a protein or enzyme 3. Turn an enzyme on or off Your Job Think about the cellular effects listed. Try your best to draw what is actually meant by those three phrases. NOTE: You should also think about how the hormone works. Meaning, does it work from outside of the cell or inside of the cell? How could you figure this out? Cell 1 Cell 2 bloodstream Cell 1 Cell 2 bloodstream 6
Hormone Classes 1. Amino acid derivatives 2. Peptide derivatives 3. Lipid derivatives Which of these are likely to work extracelluarly and why? Which of these are likely to work from inside of the cell, and why? Hint: Think about their chemical structure and the cell membrane Hormones bind to receptors Located on the cell membrane Cell 2 -amino acid and protein hormones -Or - Located within the cell (bind to receptors in the cytoplasm or nucleus) -lipid hormones Hormones that bind to receptors on the cell membrane Act as FIRST messengers by binding to receptor Activate a SECOND messenger -cyclic AMP (camp) -cyclic GMP (cgmp) -calcium ions (Ca2+) The link between the first and second messenger is a G protein G camp Peptide Hormone G camp First Messenger GPCR G-protein Second Messenger camp 7
Signaling Cascade or Signal Transduction Fancy terms for this signal relay that occurs Note that the signal is physically transduced across the lipid bilayer Usually, signal is amplified at level of second messenger ie. Release of many calcium ions from intracellular stores as the result of one hormone molecule binding Where have we seen this before? G-proteins are the link between the 1 st and 2 nd messengers G proteins have three subunits and are associated with GPCRs G-proteins exchange GDP for GTP upon receptor activation Upon activation, subunits released and then mediate variety of intracellular effects I know you are just dying to ask, But, Heidi, what might a released G-protein subunit do? I have to give you the stock answer that, well, its complicated. Depends on what flavor of G-protein is activated The three flavors or subtypes to know are: Gs, Gi, and Gq THM= different G proteins affect levels of 2 nd messengers in different ways Classes of G-proteins Gs-stimulatory, activation leads to in Adenylyl Cyclase (AC) activity, thus camp Gi-inhibitory, activity of AC, in camp Also leads to opening of K+ channels Gq - Ca2+ mobilizer, causes release of Ca2+ from cytosolic storage 8
How do the levels of 2 nd messengers in the cell change? Remember the 2 nd messengers: **cyclic AMP (camp) cyclic GMP (cgmp) **calcium ions (Ca2+) How is Ca2+ mobilized? Where might calcium come from? Gq Effects of Elevated Calcium Calcium activates kinases (molecules that phosphorylate other molecules) Calmodulin relays the message by phosphorylating other enzymes Phosphorylation cascade! Adenylate Cyclase (AC) affects camp levels AC is an enzyme that catalyzes the conversion of ATP to camp AC is activated (stimulated) by Gs subunits AC AC is inhibited by Gi subunits Gi Gs ATP camp 9
Gs proteins activate Adenylate Cyclase (AC), generating camp Adenylate Cyclase What affects might elevated camp have in a cell? Depends on the cell, but in general, camp activates kinases. These kinases go on to phosphorylate downstream effectors or channels Another phosphorylation cascade camp Activation of kinases Phosphorylation cascade Some hormones bind to intracellular receptors Lipid derived hormones diffuse across the bilayer and bind to cytosolic or nuclear receptors! Hormones that bind extracellularly Once inside the cell, these hormones primarily affect transcription of genes!! 10
What can you guess about the response time? The duration of the effect? Thyroid Hormone is Weird First, thyroid hormone is actively transported into cells, almost all cells Once inside, it will act at mitochondria! What might thyroid hormone effect here? Thyroid hormones activate enzymes Increases enzyme transcription Thyroid hormone increases metabolic rate! We will revisit diseases of the thyroid on Wednesday. But, start thinking about what you might expect to see if someone has low circulating Thyroid hormone High levels? Which person might be thinner? Colder? Organs and Glands of the Endocrine System: The major players Pituitary gland Anterior pituitary What about the hypothalamus? Posterior pituitary Thyroid Gland Parathyroid Glands Adrenal Glands Adrenal cortex and adrenal medulla Pancreas 11
The Pituitary Gland Pituitary Gland Secretes 9 major hormones Size of a pea Two lobes -posterior (neural) -anterior (glandular) Cellular Anatomy of the Pituitary Gland Hypophyseal Portal System Secretion of regulatory hormones by the hypothalamus controls secretion of anterior pituitary hormones A unique system (two capillary networks) linked together are known as a portal system Normally: artery capillary network vein 12
Hypothalamus Consequences of a Portal System ONE-WAY Efficient chemical communication Hormones go directly from hypothalamus to anterior pituitary without dilution or circulating around the body first! Anterior Pituitary ONE-WAY Hypothalamic control of Anterior Lobe of Pituitary and Negative Feedback Functions of the Hypothalamus 13
Anterior Pituitary Tropic hormones from the Anterior Pituitary have an endocrine gland as the target -TSH (Thyroid stimulating hormone) -ACTH (Adrenocorticotropic hormone) -FSH (Follicle Stim. Hormone) -LH (Leutinizing Hormone) Anterior Pituitary TRH Thyroid Stimulating Hormone (TSH) also known as thyrotropin Target gland: thyroid gland TRH from hypothalamus causes TSH release TSH Thyroid Gland Thyroid Hormone (T3) 14
Anterior Pituitary Adrenocorticotropic hormone (ACTH) Target gland: adrenal cortex Triggered by release of CRH from hypothal. Negative feedback mechanism is same Anterior Pituitary Gonadotropins Follicle stimulating hormone (FSH) Target gland: follicle Luteinizing hormone (LH) Target gland: ovary GnRH FSH or LH ovaries/follicle Anterior Pituitary Prolactin (PRL) Target gland: Mammary gland and milk release (along with oxytocin) Prolactin production is under constant inhibition by dopamine!! Anterior Pituitary Growth hormone (GH) or somatotropin Target: almost all cells are capable of responding to GH Skeletal muscle and cartilage are very sensitive Triggered by the release of: GHRH, inhibited by GHIH (somatostatin) Interesting side effect of classical antischizophrenic medications. 15
How does Growth Hormone get its name? Causes production of growth factors that stimulate increased uptake of amino acids Directly stimulates stem cell division (epithelial and connective tissue) Stimulates breakdown of glycogen by liver, which increases glucose in the blood Pars intermedia (the middle section of the pituitary) virtually nonfunctional in humans aka scientists haven t figured out what it does yet! Releases melanocyte stimulating hormone (MSH) Target? Important during development and pregnancy Inhibited by dopamine MSH in adult human is stimulated locally by sun, etc. Posterior Pituitary Nervous tissue, contains axons of hypothalamic neurons These neurons secrete ADH and oxytocin into bloodstream 16
Posterior Pituitary Anti-diuretic hormone (ADH) water saver hormone Special hypothalamic neurons monitor the blood concentration (osmoregulators) ADH targets the kidney tubules -urine volume decreases, blood volume increases ADH also works at peripheral blood vessels, where it mediates constriction, thereby increasing blood pressure Posterior Pituitary, ADH and alcohol Why does drinking alcohol increase the desire to pee?? Alcohol inhibits ADH release Now to explain the phenomenon of breaking the seal Posterior Pituitary Oxytocin -stimulates smooth muscle contraction of the uterine wall for delivery -also stimulates the ejection of milk During labor, oxytocin may be released by uterus and/or fetus! Posterior Pituitary and Orgasm Females: increases smooth muscle contraction in uterine walls Males: increases smooth muscle contraction is sperm duct walls, sperm in ready position 17