Lecture 2 Flashcards
Which mammalian hormones have feedback regulation of synthesis
Steroids
Thyroxine derivatives
Peptides and proteins
Catecholamines
Three major classes of human hormones
Protein and peptide hormones
Steroid hormones
Tyrosine derivatives
How long is storage of preformed steroid hormones
Very little
Storage of preformed thyroxine
Several weeks
Storage of peptide hormones
One day
Storage of catecholamines
Several days, in adrenal medulla
Mechanism of secretion, steroids
Diffusion through plasma membrane
Thyroxine mechanism of secretion
Proteolysis of thyroglobulin
Mechanism of secretion peptides
Exocytosis of storage vesicles
Mechanism of secretion catecholamines
Exocytosis of storage vesicles
Binding to plasma proteins - steroids
Yes
Binding to plasma proteins - thyroxine
Yes
Binding to plasma proteins - peptides
Rarely
Binding to plasma proteins- catecholamines
No
Lifetime in blood plasma - steroids
Hours
Lifetime in blood plasma-thyroxine
Days
Lifetime in blood plasma-peptides
Minutes
Lifetime in blood plasma- catecholamines
Seconds
Time course of action-steroids
Hours to days
Time course of action-thyroxine
Days
Time course of action-peptides and proteins
Minutes to hours
Time course of action-catecholamines
Seconds or less
Receptors -steroids
Cytosolic or nuclear
Receptors - thyroxine
Nuclear
Receptors - peptides and proteins
Plasma membrane
Receptors - catecholamines
Plasma membrane
Mechanism of action - steroids and thyroxine
Receptor-hormone complex controls
Transcription and stability of mRNAs
Mechanism of action - peptides
Hormone binding triggers synthesis of Cytosolic second messengers or protein kinase activity
Mechanism of action - catecholamines
Hormone binding causes change in membrane potential or triggers synthesis of Cytosolic second messengers
Two classes of hormone receptors
Intracellular
Cell surface
How does negative feedback system work
A product sends message back to source to cut back production
How does positive feedback loop work
Product sends message bsck to source to make more product
How is parturition an example of a positive feedback loop
Posterior pituitary makes oxytocin, which produces uterine contraction, which creates a cervical stretch as baby’s head is pushed forward. Stretch sends positive feedback to posterior pituitary to make more oxytocin and to uterus to contract more
How does two hormone feedback system work
As one increases, the other decreases and vice versa
What controls activity of thyroid glands, adrenal cortex, and gonads
Feedback effects of their circulating hormones on the hypothalamic-pituitary axis
What controls pancreas and parathyroid
Feedback signals of regulated variable
Six experimental approaches used in endocrinology research
Surgical approach Parabyosis Immunological- immunolocalization and radioimmunoassay Ligand receptor binding Bioassay Gene manipulation (molecular biology)
Explain the Berthold experiment with roosters (concept of compensatory hypertrophy) surgical approach
Group I had both testes removed
Group II had one testis replaced
Group III had one testis exchanged
Results
I. comb and wattles small, no interest in hens, weak crow, listless fight behavior
II. Comb and wattles normal, interest in hens, normal crow, aggressive fight behavior, testis larger than in controls
III. Same as II
Parabyosis
The joining of two individuals
Example of Parabyosis experiment
Surgically achieved shared circulation in mice. Compensatory organ hypertrophy.
Immunolocalization
Using immunologic techniques, including specific antibody, to identify location of molecules or structures within cells or tissues
Radioimmunoassay
Technique for determining antibody levels by introducing an antigen labeled with a radioisotope and measuring the subsequent radioactivity of the antibody component
Immunodeficiency assay
Antibodies immobilized into a plastic surface are used to capture the target antigen
Second antibody linked to enzyme is then added. It binds to a different location on target antigen.
Plate wells are washed to remove unbound components
Substrate is added
Enzymatic reaction is stopped in order to establish a consistent time period for all wells. After stopping, color is measured.
Color generated is directly proportional to the amount of analyze present.
Concept of immunometric assay
Antigen specific antibody is attached to a solid-phase surface
Test specimen is added, which may or may not contain the antigen
An enzyme labeled antibody specific to the antigen is added
Chromogenic substrate is added, which in the presence of the enzyme, changes color.
What is relationship between hormone binding and biological response when there are spare hormone receptors
The concentration of hormone can be smaller if there are spare receptos to achieve the same amount of binding as it would take with fewer receptors
Amino acid derivatives that interact with cell surface receptors
Epinephrine and histamine
Where does epinephrine originate? Major effects?
Adrenal medulla
Increase in pulse rate and blood pressure, contraction of most smooth muscles, glycogenolysis in liver and muscle, hydrolysis in adipose tissue
Histamine origin and effects
Mast cells
Dilation of blood vessels
Do prostaglandins react with cell surface receptors
Yes
What are prostaglandins a derivative of
Arachnid panic acid
Origins and major effects of prostaglandins
Most body cells
Contraction of smooth muscle
Examples of peptide hormones that interact with cell surface receptors
Follicle stimulating hormone (FSH) Glucagon Insulin LH releasing hormone Luteinizing hormone
Source and effects of FSH
Anterior pituitary
Stimulates growth of oocyte and ovarian follicles and estrogen synthesis by follicles
Sources and effects of glucagon
Pancreas alpha cells
Stimulates glucose synthesis and glycogen degradation in liver; lipid hydrolysis in adipose tissue
Source and effects of insulin
Pancreas beta cells
Stimulates glucose uptake into fat and muscle cells; carbohydrate catabolism, stimulates lipid synthesis by adipose tissue; general stimulation of protein synthesis and cell proliferation
Source and effects of LH releasing hormone
Hypothalamus, neurons
Induces secretion of LH by anterior pituitary
LH source and effects
Anterior pituitary
Maturation of oocyte, stimulates estrogen and progesterone secretion by ovarian follicles
Examples of peptide growth/differentiation factors that interact with cell surface receptors
Epidermal growth factor
Nerve growth factor
Platelet derived growth factor
Source and effects of insulin like growth factor 1
Liver and other cells
Autocrine/paracrine growth factor induced by somatotropin; stimulates cell growth and division and glucose and amino acid uptake, increase in liver glycogen synthesis
Nerve growth factor origin and effects
All tissues innervated by sympathetic neurons
Growth and differentiation of sensory and sympathetic neurons
Platelet-derived growth factor origin and effects
Platelets and cells in many other tissues
Chemotaxis of connective tissue cells and inflammatory cells; development and survival of cells in the nervous system;wound healing
What are the two types of cell surface receptors
Linked to TK
Linked to G proteins
What are the two subgroups of receptors linked to TK
Growth factor receptors intrinsic TK
Cytokines receptors recruit TK
Two types of subgroups of receptors linked to G proteins
Adenylate cyclase
PLC
Two types of intracellular receptors
Class 1 Cytosolic
Class 2 nuclear
Mechanism of action of G protein linked receptors
- Ligand binds with cell surface receptor
- Conformational change in receptor
- Receptor binds to G alpha protein
- Induces conformational change in G alpha
- GDP bound to G alpha is replaced by GTP and the subunit disassociates from Gbetagamma
- G alpha binds to adenylyl Cyclase and activates cAMP synthesis
- Hormone dissociates
- Hydrolysis of GTP to GDP causes G alpha to dissociate from adenylyl Cyclase and bind to Gbetagamma
Five second messengers
3',5'-cyclic AMP 3',5'- cyclic GMP 1,2- diacylglycerol Inositol 1,4,5- triphosphate Calcium ion
What does binding of growth hormone do to receptor? What does it recruit?
Dimerization of receptor
Recruits cytoplasmic tyrosine kinase,JAK-2
Where does JAK-2 bind in GH receptor
Juxta membrane region of intracellular domains of receptor, known as Box 1
What does JAK-2 activate
MAPK
What does JAK-2 phosphorylate
Tyrosines on STATs
They form dimers and undergo translocation into nucleus, where they act as transcriptional regulatory proteins
How does GH rapid insulin-like metabolic effects
IRS-1 and IRS-2 are phosphorylated by JAK-2 and recruit p85 subunit of P13 kinase
What is the structure of the insulin receptor
Disulfide bridges link the alpha subunits to one another and also to two identical beta subunits, which cross the plasma membrane.
What does insulting binding to receptor result in?
Insulin binding to alpha subunits in auto phosphorylation of the intracellular domains of the beta subunits
What does phosphorylation of insulin receptor beta subunits cause
Docking of IRS-1 or IRS-2, which can then be activated by tyrosine phosphorylation P
How does MAPK pathway work in insulin receptor
Grb2 links IRs-1 to the GDP/GTP exchange protein, Sos. The Sos Grb2 complex gets near small G protein RAs, located in plasma membrane. This triggers RAs by the exchange of GTP for GDP.
Serine/threonine kinase enzyme Raf activates a tyrosine/serine/threonine kinase enzyme (MEK), which activates a multifunctional MAPK, which targets proteins located in multiple regions of cells
What can MAPK modulate in insulin receptor
C-fos and c-junk and can also release arachidonic acid by the action of phospho lipase A2
What do IRS1 or 2 activate via insulin receptor
The P13 kinase pathway which enhances glucose transport
Mechanism of steroid hormone receptor
Serum binding protein transports steroid hormone to vicinity of membrane
Hormone diffuses through membrane
It bind with Cytosolic receptor
Enters nucleus and influences trancription
Mature MRNA exists nucleus and goes to ribosome complex, where it is translated into a protein
