lecture 1a- hormones Flashcards
What is the definition of a hormone?
A substance in the body that transmits a signal to produce an effect to alteration at the cellular levels
Hormones are regulate…
gene expression, reproduction, growth, senscence(aging) and maintain homeostasis
hormones have major _____ and ____
Major glands and major organs
What are the major hormone glands?
hypothalamus, pituitary, thyroid, parathyroids, adrenals, pineal body
What ate the major hormone major organs?
Reproductive organs (ovaries and testes), pancreas and kidneys
What are the types of hormones?
protein, amino acid derived and steroid
How do endocrine hormones worK?
hormone released into bloodstream to contact distant cell
How does paracrine hormones work?
hormone released to contact a neighboring cell
How does autocrine hormones work?
hormone released onto itself
Explain the hormonal cascade:
- First a environmental or internal signal signals the CNS to the limbic system so your HYPOTHALAMUS receives the signal and recreates releasing hormones (ng=very small).
- Then the releasing hormones act on the anterior pituitary to release the tropic hormone (ug= a little more).
- Then the tropic hormone acts on the target “gland” to release the ultimate hormone (mg) to create systemic effects
hormones always work in a _ and is magnified with every release (X_)
hormones always work in a cascade and is magnified with every release (X1000)
If there is too much ultimate hormone, what happens?
There is a negative feedback loop to the ant pituitary or hypothalamus
While most hormones go through the anterior pituitary, what two hormones got to the posterior pituitary
Oxytocin (uterine contractions and lactation) and vasopressin (water balance)
Peptide and protein hormones are products of ______
Translation
Peptides hormones are relatively _____ than protein hormones
smaller
How are the peptide/protein hormone stored or synthesized?
The cell stores peptide or protein hormones in secretory granules and releases them in “bursts” when stimulated. This allows cells to recreate a large amount of hormone over a short period of time (immediate)
OR
Cell synthesizes the hormone and releases it immediately in secretory vesicles
What is one way polypeptide and protein hormones are synthesized (e.g. POMC gene)
synthesis: gene encodes for several hormones
- protein get cleaved into small sections (peptides)
- These hormones independent of each other and they can bring effect
How are vasopressin and oxytocin synthesized
synthesis: gene encodes precursor for hormones
- Gene is cleaved to make hormone but the hormone is so small It needs a carrier. In the same gene, Neurophysin (II for vasopressin & I for oxytocin) is cleaved out to be the carrier protein
- The same gene has the carrier protein and hormone
-
Prepro-vasopressin–> pro-vasopressin–> vasopressin
*same for oxytocin
How is insulin synthesized?
Synthesis: gene encodes precursor for hormones
- In ER: first cleavage of signal sequence in prepro-insulin to get pro-insulin. The A and B chains have disulfide bridges.
- In golgi: cleavage of the c-peptide (connecting peptide) and then you have mature insulin
What is the function of insulin and what does it stimulate
facilities uptake of glucose by cells; stimulates lipid and glycogen formation to decrease blood glucose levels
What happens with diabetes and in type one & two
no glucose uptake;pateitn manifests high circulating glucose levels (hyperglycemic)
- Type 1: juvenile onset (kids)–> pancreatic cells destroyed-no production of insulin
- Type 2: adult onset–> body does not produce enough insulin and/or does not utilize insulin efficiently. INSULIN RESISTANCE
What is the txt for type one and two
one: insulin injections
two: diet and exercise; drugs targeting organs involved in glucose metabolism; chronic cases-insulin injections
What are the four different ways drugs treat diabetes
- enhance insulin acid in peripheral tissues
- drugs that suppress endogenous glucose production
- enhance endogenous insulin secretion
- delay the absorption of carbohydrates from the GI tract
What are amino acid derived hormones
catecholamines: hormones and NT
Thyroid hormone
What is the example of amino acid derived hormones
norepinephrine (noradrenaline) and epinephrine (adrenaline) are synthesized from phenylalanine and tyrosine in the adrenal medulla and released in response to stress
What does NEP and EP do?
accelerate heartbeat, increase BP and blood flow to heart and lungs
What is the process of NEP and EP to be released
- STRESS signal to hypothalamus to release ACTH (Adrenocorticotropic hormone) –> cortisol (steroid hormone)
- Cortisol will initiate synthesis of PNMT (Phenylethanolamine N-methyltransferase) to take NEP to EP to then secrete EP out of the cells to see response
NEP is from Tyr
what is the epinephrine mode of action?
G- protein coupled receptor to cause second messengers to increase thranscription–> biological action
Where is the thyroid hormone synthesis occur?
Follicular space of the thyroid gland
What are the steps of the thyroid hormone
- thyroglobulin contains about 100-120 tyrosine residues
2.Uptake of Iodide (I-)–> diet - Oxidation og iodine (I)
- Iodination of thyroglobulin –> on tyrosine residues
- Formation of MIT (monoiodotyrosine ~ T1) and DIT (diiodotyrosine~T2)
- Polymeric molecules T3 (triiodothyronine) and T4 (thyroxine; tetraiodothyronine)
- Secretion
what is the active thyroid hormone and storage
- T3 is active
- T4 is storage
Where do we get iodide?
- Seafood, eggs, milk, dietary supplements and salt in diet
- 150g in adults
What is your thyroid hormone responsible for?
Responible for rate of your metabolism
Through the graph on the PP, explain thyroid hormone synthesis
What is the enzyme for thyroid hormone
Peroxidase
What does the hypothalamus secrete for thryoid hormone to situmlate the pituitary
Secretes TRH
What does the pituitary release to stimulate the thyriod
Releases TSH
Where is T4 converted to T3
Peripheral tissues
What is the inactive thyroid hormone? and what can it do?
Reverse T3
Can dock with thyroid receptors and compete with T3
What is the function of thyroid hormone?
- Increases energy utilization
- oxygen consumption
- growth and deveplopment
How does T3 work?
- T3 binds to thyroid hormone transporter
- Binds to thyroid response element on a gene and recruits cofactors (coactivators or corepressors)
- When bound all together, will intitate thranscripiton of gene
What are the thyroid hormone disorders?
Graves disease: hyperthyroidism
Hashimoto’s disease, chronic lymphocytic: Hypothyroidism
What happens in hyperthyroidism
- Tyroid stimulating immunoglobulin binds to the thyroid-stimulating hormone (TSH) receptor on the thyroid cell membrane and stimulates the thyroid gland
- Thus, it stimulates thyroid homrone synthesis and thyroid gland growth causing **hyperthyroidism and thyromegaly **
- The key is **increased production of T3 **
- Negative feedback response is for TSH so T3 remain high due to thryoid stimulating immunoglobulin
- **Disgnosis may have low TSH, high t3, t4 **
Why do we still have high T3 even though we have a negative feedback response
- Negative feedback response is for TSH so T3 remain high due to thryoid stimulating immunoglobulin
What is the lab diagnosis result hyperthyroidism
- **Disgnosis may have low TSH, high t3, t4 **
What are the symptoms of hyperthyrodism?
- nodules on thyroid-goiter
- restlessness
- anxiety
- sweating
- bulging eyes
What is the treatment of hyperthyroidism
- Anti-thyroid drug Tapazole
- Surgical removal of thyroids
What is the casue of hashimoto’s disease
- underactive thyroid gland
- enlarged, inflamed thyroid
What is the symptoms of hashimotos
- weight gain
- dry skin
- low heart rate
- depression
Where do we see 95% of casues of hashimotos
Women between 30-50
What is the diagnosis of hashimoto’s
High titers of antibodies to thyroglobulin, thyroid peroxidase and TSH receptor
What is the txt of hashimoto’s
thyroid hormone pills
By varying the consitiutents od the steroid ring, steriods are metabolically _______
Interconverted
All steriod hormones are made from ____
Cholesterol
How many classes are there for steroid hormones
- 5 classes: mineralocorticoids, glucocorticoids, androgens, estrogens, progestogens
- the receptor defines the classes which structure defines receptor specificity
What is an example of mineralocorticodis
aldosterone being most prominent
What is a major glucocorticoids
cortisol
What is an example of androgens
testosterone
What are two examples of estrogens
estrodiol and estrone
what is progestogens also known as and an example
- Also known a progestins
- Ex: progesterone
What is the function of aldosterone?
acts maninly in the functional unit of the kidneys to aid in the consveration of sodium,secretion of potassium, water retention and to stabilize blood pressure
What is the function of cortisol
- Metabolic: increases insuilin resistance, increases gluconegogenesis, lipolysis
- Immunosuppressive: inhibits leukotrienes and prostaglandins, blacks histamine release from mast cells, blocks IL-2 production
- **Maintains blood pressue **
Glucocorticoids is what type of hormone
steroid
____ suppress immune and inflammatory responses mediated by cytokines
Glucocorticoids
What is the normal route of the inflammatory rxn in our body?
- Within the cell, you have a complex of NF-KB +IKBa and when they are joined together they are inactive.
- When TNF binds to the receptor, it separates the complex so NFKB(transactivator) can be active and turn on transcription of genes for cytokines
What is the process when the glucorticoids are introduced into the cell?
- GC binds to the receptor, then turn on transcription for the gene IKBa
- IKBa then can bind to NKKB so it will be inactive and stop hyper-cytokines
What is the clinical uses of glucocorticoids?
- Allergic rhinitis
- Rheumatoid arthritis
- Asthma
- MS
- carpal tunnel syndrome
- dermatitis
- COPD
- Osteoarthritis
- Gout
- Psoriasis
- Inflammarory bowel disease
- Sinusitis
- Lupus erythematosus
What is the base of sex hormones (androgen, estrogen, progesterone) ?
cholesterol
are steroid hormones, hydrophobic or hyrdophillic?
hydrophobic
Give details about steroid hormones
- newly synthesized steroid hormones are rapidly secreted from the cell with little if any storage
- biologically active steroids are transported in the blood by albumin, sex hormone binding globuin (SHBG) and corticosteroid-binding globulin (CBG)
- Steroid hormones are typically eliminated by inactivating metabolic transformations and excretion in urine or bile
What are the diseases related to steriod hormones
Cushing and congenital adrental hyperplasia
What are the details of congenital adrenal hyperplasia (CAH)
- group of autosomal recessive diseases resulting from mutations of genes for enzymes in synthesis of steroid hormones in adrenal glands
- adrenal hyperplasia as ACTH continues to stimulate steroid production due to lack of feedback inhibition from cortisol
- Symptoms:exccessive loss of salt, ambiguous genitalia in infants
Say the details about cushing disease
- HIGH CORTISOL LEVELS
- symptoms: growth retardation, hump in shoulder, and weight gain
- Medications to control excessive production of cortisol at the adrenal gland: ketoconazole (nizoral), mitotane (lysodren), metyrophone (metopirone)
Explain cyclic hormonal signaling with serotonin and melatonin
Explain the cyclic hormonal signaling with the ovarian cycle
Explain hormone transport
- once a hormone is secreted by an endocrine tissue, it generally binds to a specific plasma protein carrier with the complex being disseminated to distant tissues
- plasma carrier proteins exist for all classes of endocrine hormones
- most peptide hormones circulate freely without carrier proteins. Carrier proteins for peptide hormones such as IGF prevent hormone destruction by plasma proteases
- Carriers for their small hydrophillic amino acid-derved hormones prevent their filtration through the renal glomerulus, greatly prolonging their circulating half-life
- Carriers for steroid and thyroid hormones allow these very hydrophobic substances to be present in the plasma at concentrations several hundred-fold greater than their solubility in water would permit
Explain hormone clearance
- Hormones can be inactivated in the liver through hydropxylation or oxidation and/or glucuronidation, sulfation or reduction with glutathion reactions and excreted via kidney
- Hormones can be degraded at their target cell through internalization of the hormone-receptor complex followed by lysosomal degradation of the hormone–> when hormone is bound to receptor and all is internalized
- a small fraction of total hormone production is excreted intact in the urine and feces
- The metabolic rate of clearance of hormone is measured as the volune of plasma cleared of the hormone per unit of time
How are homrones inactivated?
Hormones can be inactivated in the liver through hydropxylation or oxidation and/or glucuronidation, sulfation or reduction with glutathion reactions and excreted via kidney
How can hormones be degraded?
Hormones can be degraded at their target cell through internalization of the hormone-receptor complex followed by lysosomal degradation of the hormone–> when hormone is bound to receptor and all is internalized
A small fraction of total hormone production is ____ intact in the urine and feces
excreted
How is the metabolic rate of clearance of hormone measured?
as the volume of plasma cleared of teh hormone per unit of time
