Rilllema Flashcards
What are the the different types of cellular regulation of hormones?
- Intracrine: active principals act IN the same cell which they are produced; Example: Follicles of female reproductive system
- Autocrine: active principals act ON the same cells from which they were secreted ; Example: Growth factors
- Paracrine: active principals act on ADJACENT cells from which they are secreted
- Neurocrine: active principals are released from axons and function on dendrites ; Example: at NMJ
- Endocrine: hormones produced in certain cells and function at distant targets
What are the different sources of hormones?
- Head: pineal gland, pituitary gland, hypothalamus
- Neck: thyroid gland, parathyroid gland
- Abdomen: pancreas, adrenal gland, gut, gonads
- Skin: secretes vitamin D3 (using sunlight)
- Heart: secretes ANF (anthypertensive hormone that causes vasodilation)
- Fat Cells: secrete leptin (inhibits appetite)
What are the hormones that are secreted from the anterior pituitary (know all of the different names for them and their general function )
- Prolactin (PRL, LTH- lactotropic hormone, MTH- mammotropic hormone): Lactotroph Cells (~15%); Stimulates lactation
- Growth Hormone (GH, STH- somatoropichormone): Somatotroph Cells (~40-45%); Stimulates growth processes; Regulates plasma level of glucose, free FAs and amino acids
- Thyrotropin (TSH-thyroid stimulating hormone): Thyrotroph Cells; Stimulates thyroid gland to grow and produce thyroid hormone
- Corticotropin (ACTH, adrenocorticotropic hormone): Corticotroph Cells; Stimulates adrenal cortex and growth of adrenal gland
- Follicle Stimulating Hormone (FSH): Gonadotroph Cells; Stimulates follicle growth in the ovary; Stimulates spermatogenesis in the testis
- Luteinizing Hormone (LH, ICSH- interstitial cell stimulating hormone): Gonadotroph Cells; Stimulates ovulation; Stimulates steroid hormone production in ovary and testis
What are the hormones secreted from the intermediate lobe of the pituitary?
Melanocyte Stimulating Hormone (MSH):
Disperses melanin granules in the skin
Virtually non-functional in humans (MSH is not produced in humans normally)
What are the hormones secreted from the posterior pituitary? what is their roles?
Hormones synthesized in the paraventricular and supraoptic nuclei of the hypothalamus
- Oxytocin: stimulates milk letdown and partuition
- Antidiuretic Hormone (ADH, Vasopressin): stimulates water reabsorption in nephrons
What are the hormones released from the hypothalamus?
hormones secreted here regulate the anterior pituitary; carried to anterior pituitary form the capillary bed at the median eminence via long portal vessels
- Growth Hormone Releasing Hormone (GRH)
- Growth Hormone Inhibiting Hormone (GIH, Somatostatin, SRIF)
- Prolactin Inhibitory Hormone (PIH, dopamine)
- Corticotropin Releasing Hormone (CRH): increases ACTH secretion
- Thyrotropin Releasing Hormone (TRH): increases TSH secretions
- Gonadotropin Releasing Hormone (GnRH): regulates LH and FSH secretion
What hormones are secreted from pineal gland?
Melatonin: regulates reproductive cycles in lower species; may be related to jet lag in humands
What hormones are secreted from the Thyroid Gland?
- Thyroid Hormones:
A). Thyroxine (T4): precursor for T3, produced in amounts 10x higher than T3 (inactive prohormone)
B). Triiodothyronine (T3): active hormone, increases many metabolic processes - Calcitonin (CT): lowers plasma Ca++ concentration; released from C cells/parafollicular cells
What hormones is secreted from the parathyroid gland?
PTH: raises plasma [Ca2+]
What hormone is secreted from the skin?
Vitamin D: functions with PTH to raise plasma [Ca2+]
What is the endocrine function of the pancreas ? (what is secreted)
- Insulin: β cells = Lowers plasma glucose, amino acids and free FAs; Mitogenic (stimulates growth)
- Glucagon: α cells = Raises plasma glucose and free FAs
- Somatostatin: Δ cells
What hormones are secreted by the adrenal glands?
- Cortex:
A). Glucocorticoids (Cortisol): stimulates gluconeogenesis and lipolysis; zona fasciculate
B). Mineralcorticoids (Aldosterone): increases Na+ reabsorption and K+ secretion; zona glomerulosa
C). Sex Steroids (Androgens): only source of androgens in females; zona reticularis
- Medulla = Catecholamines (Epi and NE): fight or flight response (**made from tyrosine)
What hormones are synthesized/secreted in the ovaries, testes, and placenta?
- Ovaries = Estrogen, Progesterone, Inhibin
- Testis = Testosterone, Inhibin
- Placenta =
Placental Lactogen (HPL): binds to GH and PRL receptors and carries out similar functions
Chorionic Gonadotropin (hCG): maintains early pregnancy (detected by pregnancy test)
Estrogen
Progesterone
What hormones are stimulated by the liver, heart, fat cells, and stomach?
liver = IGF-1 (bone growth) Heart = ANP/ANF/ANH (vasodilation/anti-hypertensive/increased water/na release) Fat = leptin (inhibits appetite) Stomach = Ghrelin (stimulates appetite)
What are the tyrosine derived hormones?
- Catecholamines (dopamine, epi, NE)
TYR = L-DOPA = Dopamine = NE = epi - Thyroid hormones (T4/T3) synthesized on Thyroglobulin
What are the lipid homones?
- Steroids = progesterone, aldosterone, cortisol, testosterone, estrogen;
all derived from cholesterol (glucose - aceteate - cholesterol - progesterone)
vary by different number of carbons (21, 19, 18), saturation, and oxidation - Vitamin D = derived from cholesterol (UV light in skin) - to cholecalciferol (vit D) stored in liver - active vit D from kidney
- Eicosanoids = prostaglandings, leukotrienes, thromboxanes
Function as circulating hormones in some circumstances
All derived from arachadonic acid (20:4)
A). Prostaglandins: vascular actions, inflammation
B). Thromboxanes: blood clotting and other vascular actions
C). Leukotrienes: mediate allergic and inflammatory reactions
What are the peptide hormones?
1. Hypothalamic Releasing Hormones: TRH: 3 AA (smallest) GnRH: 10 AA GIH: 14 AA CRH: 41 AA GRH: 45 AA Note: dopamine is not a peptide hormone
- Anterior Pituitary Hormones:
A). Similar Peptides:
GH: 191 AA, 2 disulfide bonds, MW: 22,000
PRL: 198 AA, 3 disulfide bonds, MW: 23,000
HPL: 191 AA, 2 disulfide bonds, MW: 22,000 (not from anterior pituitary)
B). ACTH: 39 AA, MW: 4300
Derived from POMC (Proopiomelanocortin- 239 AA, MW: 30,000)
39 AA located in the center of the POMC molecule
POMC can also be cleaved to release MSH, beta endorphins
C). Pituitary Glycoprotein Hormones (FSH, LH, TSH)
2 peptide chains plus 10% carbohydrate (MW: 30,000; some of the largest hormones)
α chain is interchangeable between all 3 (97-98 AA)
β chain provides specificity
hCG is also a glycoprotein produced by the placenta (similar structure)
D). Posterior Pituitary Hormones: ADH, oxytocin (both 9 AA)
E). Calcitonin: 32 AA
F). Pancreas Hormones:
Insulin: 2 peptide chains (α- 23 AA and β-30 AA), connected by disulfide bridges
Glucagon: 29 AA (MW: 3500)
G). GI Hormones:
Gastrin: 17 AA
CCK: 23 AA
Secretin: 27AA
H). Growth Factors:
IGF-1 (Somatomedin, EGF, FGF, NGF): MW 3000-9000
I). Parathyroid Gland: PTH (84 AA)
J). Heart: ANF (28 AA)
K). Fat cells: Leptin (MW 16,000)
In general, what are the three basic ways a hormone functins?
- Alter transport processes (ie. insulin stimulates glucose transport in skeletal muscle cells and adipocytes)
- Alter genetic activity (ie. estrogen stimulates mRNA for progesterone receptor in endometrial cells; “estrogen priming”- cannot get progesterone effects unless the cells have been previously exposed to estrogen)
3, Alter enzyme activity (ie. epinephrine stimulates activation of adenylate cyclase, which increases cAMP, activating PKA and phosphorylase)
What are the types of Hormone Response?
- Direct (ie. insulin stimulates glucose transport)
- Permissive (ie. cortisol allows epinephrine to stimulate glycogenolysis)
- Synergistic (ie. PRL + insulin + cortisol needed to stimulate milk formation)
How do Intracellular receptors work? what hormones work this way?
= steroids, vitamin D, T3
Hormone enters cell where it binds receptor and then enters nucleus to alter transcription
Intracellular receptors have binding sites for hormone and for genetic material (where it is going to bind to alter mRNA transcription)
Generally, what are the different types of extracellular receptors? what types of molecules bind to them?
= peptides and catecholamines
- Channel Receptors: Example: Ca++ or Na++; Ca++ activates NOS in NO pathway
- Tyrosine Kinase Receptors: Example: Insulin
When insulin binds, cytoplasmic portion of receptor in a tyrosine kinase enzyme - Cytokine Receptors: Example: PRL, GH, leptin, ghrelin, EPO
Tyrosine kinase activity is on Janus Kinase proteins that are associated with the cytoplasmic portion of the receptor (but not part of the receptor itself) - G Protein Associated Receptors (Serpentine Receptors):
•Gs: activates adenylate cyclase
•Gi: inhibits adenylate cyclase
•Gq: stimulates phospholipase C - Guanylate Cyclase Receptor: Example: ANH
•Binding of hormone activates guanylate cyclase, GTP → cGMP → stimulates G kinase - Serine Kinase
- Phosphatase
How do calcium ions mediate an extracellular receptor response?
Ca++ much lower inside the cell than outside or in ER (Ca++ pumped out of cell and into ER)
Intracellular Ca++ is increased either by:
•Increasing membrane permeability to Ca++ (enters from outside)
•Increasing release from ER (triggered by IP3)
Once Ca++ is inside cell, binds calmodulin, and activates Ca++ -calmodulin protein kinase enzyme
How does Nitric oxide mediate an extracellular response?
Nitric Oxide: causes vasodilation
Inactive nitric oxide synthase (NOS) is activated by Ca++-calmodulin ; NO is formed from arginine using this NOS enzyme ; NO activates guanylate cyclase (GTP → cGMP → activate G kinase → physiological response
•Physiological responses include penile erection
cGMP broken down to 5’GMP by cGMP phosphodiesterase enzyme
•This enzyme inhibited by Viagra, Cialis
How does the pKA/cAMP pathway work? How does it relate to cholera and pertussis?
- Activation of Adenylate Cyclase by Gs:
•Hormone binds receptor, Gs activated (GDP exchanged for GTP on α subunit; βγ lost)
•Gsα + GTP activates AC, increasing cAMP and PKA, which phosphorylates proteins
•Cholera toxin activates Gs in GI tract by ADP ribsoylation, causing diarrhea
2.Inhibition of Adenylate Cyclase by Gi:
•Hormone binds receptor, Gi activated (GDP exchanged for GTP on α subunit; βγ lost)
•Giα + GTP inhibit AC, decreasing cAMP
•Pertussis toxin inhibits Gi in respiratory tract by ADP ribosylation
How does the Phosphatidyl Inositol cycle work?
- Hormone binds receptor, Gq activated (GDP exchanged for GTP on α subunit; βγ lost)
- Gqα + GTP activate phospholipase C in the membrane, which cleaves membrane lipid PIP2 into DAG and IP3
•DAG activates PKC, which phosphorylates proteins
•IP3 causes ER Ca++ release, which also activates PKC and Ca++-calmodulin kinase, both of which phsophorylate proteins
How do tyrosine kinases work? what hormones use this mechanism?
= Insulin, IGF-1 use this mechanism
- 2 hormones bind 2 receptors and they dimerize, causing activation of tyrosine kinase function of cytoplasmic receptor
- Autophosphorylation of receptor itself, and then phosphorylation of various intracellular proteins that carry out function of hormone (ie. PP185, IRS)
How does the cytokine system work? (janus kinase)
Essentially the same as TK mechanism
1. 2 hormones bind 2 receptors (except GH and PRL; 1 hormone binds 2 receptors) and they dimerize, however the receptor has no enzymatic activity
2. Janus Kinase proteins associated with the receptor each have 2 TK, and they become active after hormone binding and dimerization
•Once active, phosphorylate intracellular proteins to carry out affects
MAP Kinase pathway associated with this system (mitogenic processes; see Biochem notes)
What are the different types of Hormone Assays and how do they work? Explain the experimentation you can use to figure out the amount of a hormones present/active
- Bioassays: increase hormone concentration, increase response (can use this to measure hormone levels)
- RIA and EIA:
- Radioimmunoassays (RIA)
- Immunofluorescent Assays (EIA): used now, but both work the same way
Need a tagged (radiolabeled) ligand and a dissociable binder (Abs, receptors etc.)
Create a standard curve by adding a known amount of radiolabelled hormone and Ab (equal amounts) and increasing amounts of unlabelled hormone (will equilibrate, and each time a different amount of radiolabelled hormone will be bound to Ab)
Once standard curve is made, can place a serum sample in a tube with known amounts of labellled hormone and Ab, and based on the H*-Ab%, can calculate serum hormone levels
How do hormone receptor act? what are some of their typical characteristics? What does hormone response depend on?
- *Bind Very Tightly:
- Behave like antibodies (have very strong binding affinities and very low dissociation constants)
- Hormone response depends on:
1. Number of receptors
2. Number of hormone molecules
3. Affinity of hormone for receptor
Characteristics of Receptors:
- Saturable
- Specific
- High affinity (Kd= 10-8 – 10-12)
- Reversibility
- Biological actions parallel binding
-Scatchard plot yields a straight line
o[Bound Hormone] vs. [Bound Hormone]/[Free Hormone]
Straight line with a negative slope because as you increase the amount that is bound, it makes it harder to bind more hormone (increase concentration of free hormone and therefore decrease the B/F ratio)
Biassay vs. receptor binding curve
- Bioassays look at biological effect of a hormone
- Receptor binding curves: increase hormone concentration increases the number of receptors bound
When you compare these 2 curves, it is clear that maximum biological effect occurs when only a fraction of the receptors are bound (10-20%); therefore, bioassay curve shifted to the left
Spare Receptors: receptors that do not need to be activated in order to get a maximum response
What is upregulation? down-regulation? Negative cooperativity?
- Up-regulation: increase the number of receptors on target tissue
- Down-regulation: decrease the number of receptors on target tissue
- Negative cooperativity: affinity for a hormone decreases as hormone concentration increases
