Unit 3 Pathophysiology - Chapter 21 Mechanisms of Hormonal Regulation Flashcards
Endocrine general functions
- reproductive and CNS differentiation
- sequential growth and development
- coordiation of reproductive systems
- continuous maintenance of body’s internal environment
- adaptive resposne to stress
Hormones?
Released into circulation via endocrine glands, interact w/ nervous and immune systems to maintain communication + control
Negative- and positive-feedback system?
Most hormone levels are regulated by negative feedback
* in which tropic hormone secretion raises level of specific hormone => this elevated of specific hormone causes negative feedack, decreasing secretion of trophic hormone
Positive feedback systems in which elevated hromone levels increase a response which then further increase hormone secretion (seen often in reproductive hormones)
Endocrine communication
- autocrine (within cells)
- paracine (between cells)
- endocrine (between remote cells)
What are water soluble hormones
Epinephrine, norepinephrine, dopamine, glucagon, calcitonin, melatonin, thymosin, and ADH
* attach to surface receptors activates second messenger systems
* contain polypeptides
Lipid soluble hormones
- thryoxine (T4) and triiodothyronine (T3) - amine but soluble
- Steriods (cholesterol precursor) - estrogens, cortisol (glucocorticoid), aldosterone (mineralocorticoid), progestin (progesterone), testosterone
- Leukotrienes, prostacyclins, prostaglandins, thromboxanes (autocrine or paracine actions — derivatives of arachidonic acid
Direct effects and permissive effects
- obvious changes in cell function
- less obvious changes that facilitate cell fx
Hormone receptors
- located either on or in the plasma membrane
- in the cytosol
- nucleus of the target cell
Types of receptors include
* G-protein linked (agonist binds => G alpha dissociates from receptor and g beta-gamma => GTP is exchanged for bound GDP [originally all g alpha + g beta-gamma + GDP bound together] => G alpha activation (has ADP => ATP) => activate other molecules in cell)
* enzyme linked (catalytic receptors // transmembrane proteins w/ a ligand binding site + enzyme fx) —– most common is tyrosine (amino acid) kinases (regulate cell growth, differentiation, and survival) respond to growth factors (RTKs) while being to transfer phosphates from ATP (kinase), once phosphorylated can activate others. They work in pairs as well and once paired with ligands => create cross-linked dimer => activating tyrosine => cross phosphorylation => each Tyrosien will get a phosphate group => different proteins can attach to these docking points (w/ domain SH2 to bind with phosphorylated points) => signal transduction => regulate gene transcription remember Y shape with pairs
Receptor tyrosine kinases (RTKs) are a subclass of tyrosine kinases that are involved in mediating cell-to-cell communication and controlling a wide range of complex biological functions, including cell growth, motility, differentiation, and metabolism.
RTKs => regulate ephrins (help guide developmental processes for tissues, nerves, vessel maturation and platelets, also bind insulin // if dysfunctional then impaired growth and differentiation (many cancers involve mutations in RTKs)
e.g Herceptin => antibody that bind and inhibit RTK in many different breast cancers
- ion gated linked — interaction with chemical signal causes opening or closing of channel
Second messengers?
- cAMP (G protein-coupled receptor w/ ligand binds to G-protein, which is bound by GTP => G protein (GTP hydrolyzed) => adenylyl cyclase activated (converts ATP to cAMP => cAMP activates another protein => cellular response)
* c - cell growth, a - adenylyl cyclase (enzyme), p - protein kinase A
* Mobilize sotred energy (b-adrenergic lipolysis, glycogenolysis)
* vasopressin-mediated water retention
* parathyroid-hormone mediated calcium homeostasis
* response to catecholamiens (b-adrenergic) - cGMP
* Nitric oxide => reacts w/ enzyme sGC (Soluble guanylyl cyclase) => converts GTP into cGMP => activates protein kinase G causing:
* Vasodilation via activation of myosin phosphatase (l/t release of ca++ from intracellular stores in smooth muscles) // starts off with nitric oxide being produced in neighboring endothelial cells before diffusing into smooth muscle cells to activate sGC
* transcription factors => affect gene expression
* VASP => inhibition
* e.g Viagra can restore nitric oxide/cGMP signaling - Calcium
* transient increase in cytoplasmic ca++ d/t hormone binding and signaling molecules
* G-protein linked receptor activated => Gq (alpha) subunit w/ ATP activates phospholipase C-beta (b) => breakdowns PIP2 in membrane => creates 2nd messengers (IP3 - hydrophillic in cytoplasm + DAG - lipophilic in menbrane) => IP3 binds to ER or SR (muscle cells) causing release of Ca++ from lumen => DAG + ca++ ==> activates kinase C => cellular responses
note: IP3 can also get ca++ From calciosome [calcium storage organelles OR via cAMP-dependent phosphorylation Ca-channels**
- Also ca++ can bind with calmodulin, a regulatory protein ==> cell cycle, intracellular signaling, muscle contraction, NT release, metabolism, inflammation/immune
g-protein receptors types?
Gs (Gs-alpha) subunit activates cAMP (adenyl cyclase)
Gi (Gi-alpha) subunit inhibits cAMP (adenyl cyclase)
Water-soluble hormones general
act as first messengers, bind to specific receptors => signal transmitted into cell by action of 2nd messengers
Lipid-soluble hormones
- Steroid and thyroid hormones
- can have rapid (nongenomic) effects by binding to plasma membrane or receptor or crossing plasma membrane; often they bind to cytoplasmic proteins or diffuse directly into cell nucleus to bind to nuclear receptors
Hypothalamic-pituitary axis (HPA)
- Hypothalamus (above) regulates anterior pituitary fx by secreting releasing hormones into portal cirulation
- pituitary gland consists of anterior and posterior connected to CNS through hypothalamus
Hypothalamic hormones
- Dopamine - inhibit release of prolactin
* Substantia nigra + ventral tegemental area (VTA) - TRH —- thyroid stimulating hormone (TSH) [target thyroid gland] - release thyroxine (T4) and triidothyronine (T3) => metabolic rate
- Corticotrophic releasing hormone (CRH) - cause ACTH (adrenocorticotrophic hormone) to be released from pituitary gland => activate release of cortisol from adrenal glands (top of kidneys) => catabolic hormone/anti-inflammatory hormone — cortex
* activate catecholamines (epinephrine and norepinephrine) => increase HR/BP, liver converts glycogen to glucose then goes into blood, bronchiole dilation, decreased digestive/urine output, increased metabolic rate
* Chronic stress —- retention of Na+ and h2o, increased volume+BP, proteins+fats broken down, increased blood glucose, suppressed immune system
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* CRH => endorphins (endogenous opioids released by anterior pituitary gland)
@regulate stress response, inhibit pain during acute stress // interact w/ dopamine (mood, food intake, sex) - Substance P (released from sensory nerves in skin, muscle, and joints and inflammatory cells - macrophages, eosinophils, lymphocytes, dendritic cells) triggers an inflammatory response by dilating neighboring blood vessels ==> inhibits ACTH release and stimulates other hormones
- ADH and oxytocin (made in hypotalamus and stored in posterior pituitary)
* ADH - retain water, Na+, vasoconstriction (baroreceptors, low BP)
* Oxytocin (during labor, breastfeeding, and sexual activity, including touch, stroking, warm temp) ==> binds to oxytocin receptors (released from posterior pituitary) ===> love hormone (arousal, trust, romantic attachment, mother-infant bonding)
High doses of ADH administered as medication?
Induces vasoconstriction
Oxytocin fx?
- Uterine contraction and lactation
- Men - sperm motility
- Antidiuretic effect similar to ADH
