Lecture 1 (endocrine)-EXAM 5 Flashcards
What does pineal gland, parathyroid glands, thymus and kidneys do?
- pineal: melatonin
- Para: Ca regulation
- Thymus: T cell immunocomp.
- Kidneys: renin and EPO
What are non classical hormone producing glands?
- Central nervous system
- Kidneys
- Stomach
- Small intestine
- Skin
- Heart-> ANP
- Lung-> ACE with RAAS
- Placenta
- Adipocytes-> Leptin
For me to remember: CLASPS HS
- What is the definition of a hormone?
- Although many hormones travel by this mechanism, we now realize that there are many hormones or hormone-like substances that play important roles in what?
- Definitions of hormones usually included a phrase indicating that these substances were secreted into the bloodstream and carried by the blood to a distant target tissue.
- Although many hormones travel by this mechanism, we now realize that there are many hormones or hormone-like substances that play important roles in cell-to-cell communication that are not secreted directly into the bloodstream.
Many hormones or hormone-like substances that play important roles in cell-to-cell communication that are not secreted directly into the bloodstream. What do they do instead?
Instead, these substances reach their target cells by diffusion in the interstitial fluid
What are the different types of hormones?
- Hormones initiate a cell response by what?
- What are target cells/receptors?
- Hormone chemically bind to what?
- Only target cells for a given hormone have what
- What can there be?
- Hormones initiate a cell response by binding to specific receptors.
- Target cell: a cell whose activity is affected by a particular hormone.
- Hormone chemically binds to specific protein receptors on/in target cell
- Only target cells for a given hormone have receptors that bind and recognize that hormone
- There can be local transformation of a hormone within its target tissue from a less active to a more active form.
- How do water soluble hormone work?
- What base type is it?
- second messenger activates various proteins inside cell
- protein-based hormone structure e.g insulin
Hydrophillic or lipophobic
For lipid soluble hormones, what does it cause and what are examples?
- direct gene expression
- e.g. steroid/thyroid hormones
What are the four major types of receptors?
- Ligand-gated ion channels (“ionotropic receptors”-> bind and open). For example, nicotinic acetylcholine receptor.
- G-protein coupled receptors. (bind+ enzyme rxn)
- Catalytic receptors. (plasma receptor)
- Intracellular receptors. (lipid hormones)
Hormone binding to a receptor can lead to changes in cellular function via what (3)
i. Altered membrane voltage.
ii. Phosphorylation/dephosphorylation of target proteins. (via kinases + phophases)
iii. Altered gene expression (open up DNA for specific gene to make specific protein)
What are the functions of intracellular second messengers? (3)
- Connect the process of hormone-receptor binding to changes in cell function.
- Amplify the hormone signal. (increase enzymes, increase proteins)
- Provide integration of simultaneous hormone signals.
There are several second messenger pathways controlled via what?
heterotrimeric G-proteins
Coupling of the hormone-receptor complex to generation of intracellular second messengers by heterotrimeric G proteins. How does this work (think of picture)?
What are the three major eicosanoid synthesis pathways?
- Cyclooxygenase pathway produces thromboxanes, prostaglandins, and prostacyclins (big in regulating inflammation+trigger mucus-> reason why when we take a lot of nsaids, you get ulcers)
- Lipoxygenase pathway produces leukotrienes
- Epoxygenase pathway produces hydroxyeicosatetraenoic acid (HETE) and cis-epoxyeicosatrienoic acid (EET) compounds.
Several anti-inflammatory drugs inhibit the synthesis or actions of eicosanoids.
* What are examples?
- corticosteroids inhibit arachidonic acid
- NSAIDS inhibit cyclooxygenase
- lukast” drugs inhibit lipoxygenase
What are hormone receptors that do not interact with G proteins?
Explain how signal amplification is part of the overall mechanism of hormone action
Hormones can have multiple, and share some, actions with other hormones.
* What are pleiotropic effects?
* What is multiplicity of regulation?
- Pleiotropic effects: when a single hormone regulates several functions in a target tissue. Most hormones have multiple actions in their target tissues. Some hormones are known to have different effects in several different target tissues. (EX. Angiotension II)
- Multiplicity of regulation: The input of information from several sources allows a highly integrated response, which is of ultimate benefit to the whole animal
- Hormones are extraordinarily _ _
- One hormone molcule can do what?
- Very small stimulus can produce what?
- Hormone concentrations in blood are _
- Hormones are extraordinarily potent chemicals
- One hormone molecule can activate many enzyme molecules
- Very small stimulus can produce very large effect
- Hormone concentrations in blood are low (do not want a lot dt desensitivity and negative feedback)
What are the three hormone rhythmic patterns we need to know + examples?
Assessment of plasma hormone concentration requires what?
Assessment of plasma hormone concentration requires knowledge of any rhythmic patterns of secretion
Cortisol has what type of pattern? When is the concetration the highest?
Cortisol has a circadian (day/night) pattern of secretion, with the highest hormone concentration in the early morning hours
What are dynamic tests?
Dynamic tests to measure changes in hormone levels are often more useful than single blood samples (e.g., ACTH-stimulation test to assess cortisol secretion).
What are the three stimuli for hormone secretion? +examples
hormone regulation usually occurs via what
The mechanism is usually negative feedback, although a few positive feedback are known
What does hormone regulation through feedback control enable?
Enables endocrine cell to adjust its rate of hormone secretion to produce the desired level of effect, ensuring the maintenance of homeostasis (although sometimes this is not the goal).
Endocrine disorders can be classified as what? (3)
lassified as primary, secondary, or tertiary.
1. A primary disorder is an excess or deficiency of secretion by the target gland/cells.
2. A secondary disorder is an excess or deficiency of secretion by the pituitary gland.
3. A tertiary disorder is an excess or deficiency of secretion by the hypothalamus
What are the three classes of hormones?
Amines are kinda in the middle of peptide and steriod
Catcholamines (amines) have properties more like what? What about thyroid hormone?
Cat: peptides
Thyroid: steroids
Other small molecule hormones include what (4)
a. Serotonin, derived from amino acid tryptophan.
b. Gaseous transmitters (e.g., nitric oxide).
c. Nucleotides (e.g., adenosine at kidney).
d. Ions (e.g., Ca2+)
- Amine-derived hormones consist of what?
- Size+type?
- Formed by what?
- Synthesized by what?
- Amine-derived hormones consist of one or two modified amino acids
- small in size and often hydrophilic
- formed by conversion from a commonly occurring amino acid e.g. tyrosine
- synthesized by particular sequence of enzymes primarily localized in endocrine gland
- Polypeptide-derived hormones are what?
- Families have homolgy with what?
- Polypeptide hormones are what in advance of need?
- Polypeptide-derived hormones are diverse in size and complexity.
- families have homology with regard to amino acid sequence and structure.
- polypeptide hormones are synthesized and stored in advance of need
- Steroid hormones are derived from what?
- Steroids are type of hormone?
- Steroids are on demand or stored?
- What are examples?
- Steroid hormones are derived from cholesterol.
- Steroids are lipid-soluble, hydrophobic molecules synthesized from cholesterol.
- Steroid hormones are synthesized and secreted on demand
- Examples include aldosterone, cortisol, and androgen, secreted by the cortex (outer zone) of the adrenal glands; testosterone, secreted by the testes; and estrogen and progesterone, secreted by the ovaries and Vit D3 for Ca2+
Hormone elimination strongly influences plasma hormone concentration. Hormones removed from plasma by what (4)?
i. Metabolism.
ii. Binding in the tissues.
iii. Hepatic excretion.
iv. Renal excretion.
Hormone binding to proteins influences what?
Plasma hormone concentration
- What type of hormone is biologically active?
- Free hormone molcules can do what?
- Binding of hormone to what? what does this cause?
- Only free hormone is biologically active – this relationship is in constant flux.
- Free hormone molecules can diffuse out of capillaries and bind to their receptors at the target cell.
- Binding of a hormone to plasma proteins reduces the free concentration available.
- What are examples of hormones what are highly protein bound?
- What does protein binding increase?
* Steroids and thyroid hormones, and some peptides such as IGF-1, are highly protein bound.
* Protein binding increases half-life and provides a more stable reservoir of the hormone in plasma.
- What is half-life?
- What is metabolic clearance rate?
- Half-life is the time it takes to reduce the plasma hormone concentration by one half.
- Metabolic clearance rate is the volume of plasma cleared of a hormone per minute, calculated by dividing the rate of hormone removal from plasma by the plasma hormone concentration.
Explain the relationship between hormone secretion, carrier protein binding and hormone degradating
- Hormones can circulate how?
- Some plasma proteins that bind have higher what?
- Others, such as serum albumin bind many what?
- What does the liver synthesize?
- What do transport proteins provide?
- Hormone assays are reported in terms of what?
- Hormones can circulate either free or bound to carrier proteins.
- Some plasma proteins that bind have higher affinity for one hormone over another
- Whereas others, such as serum albumin, bind many hydrophobic hormones.
- The liver synthesizes and secretes these proteins. Changes in various nutritional and endocrine factors influence their production.
- Transport proteins also provide a relatively large reservoir of hormone that buffers rapid changes in free hormone concentrations and prevents large loss of free hormone by kidney filtration
- Hormone assays are reported in terms of total concentration (i.e., the sum of free and bound hormone)
- More than one hormone may be capable of what?
- What can this cause?
- More than one hormone may be capable of binding to a specific transport protein and can compete for a limited number of binding sites on these transport proteins.
- Thus, levels of the displaced hormone can rise due to out-competition by another hormone (Ex. important bc increase T3 will kick off T4)
Biologic response is partly determined by hormone–receptor binding kinetics
* What are the general characteristics of hormone-receptor kinetics? (3)
- The more receptors available the greater the likelihood of a response.
- The higher the receptor affinity for a hormone, the greater chance of interaction
- Circulating hormone concentration = hormone secretion vs. hormone degradation
- target cells exhibit graded responses proportional to what?
- minimal threshold concentration must be present before what?
- maximal response by the target cell is produced, and increasing what?
- target cells exhibit graded responses proportional to the concentration of free hormone present.
- minimal threshold concentration must be present before any measurable increase in the cellular response can be produced
- maximal response by the target cell is produced, and increasing the hormone concentration cannot elicit greater response.
Dose–response curves determine changes in responsiveness and sensitivity.
Changes in responsiveness are indicated by an increase or decrease in what? What are the factors that cause this?
Changes in responsiveness are indicated by an increase or decrease in the maximal response of the target tissue and may be the result of changes in one or more factors:
* number of functional target cells in a tissue
* number of receptors per cell for the hormone
* change in the specific rate-limiting postreceptor step in the hormone action pathway.
Changes in sensitivity reflect what? (2)
- an alteration in receptor affinity or, if submaximal concentrations of hormone are present
- a change in receptor number.
What is up-regulation?
Up-regulation may occur when certain conditions or treatments cause an increase in receptor number compared with normal, or if receptor number has declined.
What is down regulation?
Exposing cells to an excess of hormone for a sustained period of time typically results in a decreased number of receptors for that hormone per cell. This phenomenon is referred to as down-regulation
Example: giving exogenous hormones
- In addition to changing receptor number, many target cells can what?
- What is desensitization?
- In addition to changing receptor number, many target cells can regulate receptor function.
- Chronic exposure of cells to a hormone may cause the cells to become less responsive to subsequent exposure to the hormone by a process termed desensitization.
How do anterior pituitary hormones adenohypophysis work?
Anterior pituitary hormones are synthesized and secreted in response to hypothalamic-releasing hormones carried in the hypophyseal portal circulculation
How do posterior pituitary (neurohypophysis) hormones work?
Magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus, whose axons terminate in the posterior lobe, synthesize posterior pituitary hormones.
The neurohormones antidiuretic hormone (ADH) and oxytocin are synthesized where and how?
synthesized in neurons located in the hypothalamic paraventricular and supraoptic nuclei from the precursor peptides prepropressophysin and preprooxyphysin, respectively.
ADH and oxytocin are secreted into what?
ADH and oxytocin are secreted into the systemic blood from axon terminals in the posterior pituitary gland.
arginine vasopressin
- What does arginine vasopressin do?
- What are the two stimuli?
- Chemical mediators of AVP release what?
- AVP increase water reabsorption by what?
- Low blood AVP levels lead to what?
- Arginine vasopressin increases the reabsorption of water by the kidneys.
- Stimuli (humoral): 1) a rise in the osmolality of the blood 2) decrease in blood volume
- Chemical mediators of AVP release include catecholamines, angiotensin II, and ANP.
- AVP increase water reabsorption by the collecting ducts of the kidneys, decreased water excretion and the formation of osmotically concentrated urine.
- Low blood AVP levels lead to diabetes insipidus and the excessive production of dilute urine
oxytocin
- What does oxytocin do?
- Sensory nerves are where?
- What does oxytocin stimulate? What does this aid in?
- Where are stretch receptors? What does oxytocin stimulate in this situation?
Oxytocin stimulates the contraction of smooth muscle in the mammary glands and uterus.
Stimuli (nervous):
1) Sensory nerves in the nipple. Oxytocin stimulates contraction of myoepithelial cells, which surround the milk-laden alveoli in lactating mammary gland, aiding in milk ejection - Let-down reflex
2) Stretch receptors in cervical dilation. Oxytocin release stimulates contraction of smooth muscle cells in the uterus
What is the let down reflex?
Sensory nerves in the nipple. Oxytocin stimulates contraction of myoepithelial cells, which surround the milk-laden alveoli in lactating mammary gland, aiding in milk ejection
a physiological response to your baby’s sucking
Fill in
- Hypothalamic neurohormones control the release of what?
- How are the hormones delivered?
- What is close to the ant. pituitary gland that can be compressed?
- Hypothalamic neurohormones control the release of anterior pituitary hormones and are delivered via the hypophyseal portal blood supply.
- Optic chiasm
Fill in for the anterior pituitary hormones
What are the five major cell types and what they secrete in the anterior pituitary gland ?
- Somatotropes secrete GH.
- Thyrotropes secrete TSH.
- Corticotropes secrete ACTH.
- Gonadotropes secrete both LH and FSH
- Lactotropes secrete prolactin.
Fill in for anterior pit hormones
- What hormones are under the dominant control of stimulatory hypothalamic release factors?
- What is secretion of prolactin under? What happens to prolactin secretion if severing the infundibulum?
- What are the most common pituitary adenoma?
- Hyperprolactinemia often presents with what?
- Except for prolactin, the release of anterior pituitary hormones is under the dominant control of stimulatory hypothalamic release factors.
- Secretion of prolactin is under negative control by dopamine. Severing the infundibulum increases prolactin secretion due to loss of dopamine inhibition.
- Prolactinomas are the most common pituitary adenoma.
- Hyperprolactinemia often presents with galactorrhea (milky nipple discharge)
- All hormones in the hypothalamic-pituitary axis exhibit what? Wht does this reflect?
- Pulsatile release is needed for what?
All hormones in the hypothalamic-pituitary axis exhibit pulsatile release, reflecting the bursting patterns of nerve impulses. Pulsatile release is needed to prevent receptor downregulation and loss of sensitivity to hypothalamic release hormones
Fill in
- Explain the action of corticotropin-releasing hormone (CRH) on a corticotroph
- How does ATCH+cortisol levels change through out the day?
- What is the hypothalamic pituitary adrenal axis?
- CRH binds to membrane receptors coupled to adenylyl cyclase (AC) by stimulatory G proteins (Gs). Cyclic adenosine monophosphate (cAMP) rises in the cell, activating protein kinase A (PKA), which then phosphorylates proteins (P-proteins) that stimulate adrenocorticotropic hormone (ACTH) secretion and proopiomelanocortin (POMC) gene expression.
- Note that the amplitude of the pulses in ACTH and glucocorticoids is lower during the evening hours and increases greatly during the early morning hours illustrating the diurnal oscillation of the hypothalamic–pituitary–adrenal axis.
- Look at figure for axis
- Explain the action of thyrotropin- releasing hormone (TRH) on a thyrotroph
- What is the hypothalamic pituitary thyroid axis?
- TRH binds to membrane receptors coupled to phospholipase C (PLC) by G proteins (Gq). PLC hydrolyzes plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2), generating inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 mobilizes intracellular stores of Ca2+. The rise in Ca2+ stimulates thyroid-stimulating hormone (TSH) secretion. Ca2+ and DAG activate protein kinase C (PKC), which phosphorylates proteins (P-proteins) that stimulate TSH secretion and gene expression for the α and β subunits of TSH
- Look at figure for axis
- What is the action of growth hormone–releasing hormone (GHRH) and somatostatin (SRIF) on a somatotroph?
- How does the GH levels change through out the day?
- What is the hypothalamic– pituitary–GH axis
- GHRH binds to membrane receptors coupled by stimulatory G proteins (Gs) to adenylyl cyclase (AC). Cyclic adenosine monophosphate (cAMP) rises in the cell and activates protein kinase A (PKA), which then phosphorylates proteins (P-proteins) that stimulate growth hormone (GH) secretion and GH gene expression. Ca2+ also facilitates GH secretion. The possible involvement of the phosphatidylinositol pathway in GHRH action is not shown. SRIF binds to membrane receptors coupled to adenylyl cyclase by inhibitory G proteins (Gi), which inhibit GHRH stimulation of adenylyl cyclase.
- Pulsatile growth hormone (GH) secretion in an adolescent boy and in an adult. In the adult, GH levels are reduced as a result of smaller pulse width and amplitude rather than a decrease in the number of pulses. GH is higher at night
- Look at figure for axis
Growth and growth defects
- The GHRH-GH-IGF-1 axis is the most important for?
- What are other endocrine systems that contribute to growth?
- What is gigantism?
- What causes acromegaly?
- The GHRH-GH-IGF-1 axis most important for the growth of cartilage, bone, and muscle during linear growth.
- Other endocrine systems contribute - thyroid hormones, sex steroids, insulin, adrenal steroids, growth factors
- Gigantism results from GH secreting tumor before closure of the epiphyseal growth plates
- Excess secretion of GH after puberty results in acromegaly
Short stature has four major causes, list them
- Pituitary dwarfism caused by deficiency of GHRH, GH, or IGF-1.
- Laron dwarfism caused by unresponsive GH receptors.
- Cretinism caused by hypothyroidism.
- Acondroplasia dwarfism caused by defect in the fibroblast growth factor receptor. (GF in bone so cannot make cartilage for bone)
Thryoid:
* Supply?
* What is delivered?
* What system has direct effect on cells?
- rich blood supply
- delivery of thyroid-stimulating hormone (TSH), iodide, and substrates to the thyroid gland.
- adrenergic system (SNS can have effect) have direct effects on cells
- The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), play key roles in what?
- The thyroid hormones exert their regulatory functions by what? What does this affect?
- The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), play key roles in the regulation of body development and govern the rate at which metabolism occurs in individual cells. (Development+ metabolism+energy lvls)
- The thyroid hormones exert their regulatory functions by influencing gene expression and affecting the developmental program and amount of cellular constituents needed for the normal rate of metabolism
Explain the five steps in the synthesis and secretion by follicular cells of thyroid hormones
- Step 1: Iodide trapping is uptake of I− ions from the blood via a Na+/I−cotransporter.
- Step 2: Thyroglobulin is synthesized and secreted into the colloid by exocytosis. This large protein contains tyrosyl groups, which will be iodinated.
- Step 3: Iodination and conjugation of tyrosyl residues on thyroglobulin, catalyzed by thyroid peroxidase.
- Step 4: Endocytosis of thyroid colloid into the follicular cells and release within the lysosomal pathway of T4, T3. Incompletely iodinated residues diiodothyronine (DIT) and monoiodothyronine (MIT) are recycled. -> END WITH T3+T4
- Step 5: Secretion by exocytosis into the extracellular fluid of T4 and T3. Ninety percent of secreted hormone is T4, and the remaining 10% is T3.
Most of the T4 and T3 molecules that enter the bloodstream (~70% and 80%, respectively) become what?
noncovalently bound (not too strong) to thyroxine- binding globulin (TBG)
Peripheral tissues metabolize thyroid hormones
- Deiodination reactions in what?
- Enzymes that catalyze the various deiodination reactions are what?
- 5′-deiodination of T4 produces what?
- Both T4 and T3 undergo enzymatic deiodinations to do what?
- Deiodination reactions in peripheral tissues both activate and inactivate thyroid hormones.
- Enzymes that catalyze the various deiodination reactions are regulated, resulting in different thyroid hormone concentrations in various tissues under different physiologic and pathophysiologic conditions.
- 5′-deiodination of T4 produces physiologically active T3
- Both T4 and T3 undergo enzymatic deiodinations to inactivate them, especially in liver & kidneys
- Thyroid hormone synthesis and secretion are controlled by what?
- What is essential for the synthesis of thyroid hormone?
- Anterior pituitary
- Dietary iodide
- If the diet is severely deficient in iodide, as in some parts of the world, what happens?
- Enlargement of the thyroid gland increases what?
- If the diet is severely deficient in iodide, as in some parts of the world, the amount of iodide available to the thyroid gland limits T4 and T3 synthesis.
- As a result, the concentrations of T4 and T3 in the blood fall, causing a chronic stimulation of TSH secretion, which, in turn, produces a goiter.
- Enlargement of the thyroid gland increases its capacity to accumulate iodide from the blood and to synthesize T4 and T3.
Thyroid hormones mainly act via what?
nuclear receptors expressed in all body tissues,
Thyroid hormones mainly act via nuclear receptors expressed in all body tissues, what are the major effects?
i. Increases basal metabolic rate by simultaneously stimulating anabolic and catabolic processes to produce heat.
ii. Increases Na-K-ATPase activity.
iii. Increases expression of β -adrenergic receptors.
How can T3 influence cell differentiation?
T3 can influence cell differentiation by regulating the kinds of proteins produced by its target cells and can influence growth and metabolism by changing the amounts of structural and enzymatic proteins present in the cells
Thyroid Deficiency
- What happen if there are thyroid deficiency during prenatal and postnatal?
- Deficiency usually detected in newborns and what is given?
- Deficiency inhibits what?
- Basal metabolic rate (BMR) can be used clinically to assess what?
- Deficiency causes slowed what?
- How is thyroid hormones regulate?
- Deficiency during prenatal and postnatal periods of brain differentiation and maturation results in mental retardation, impaired growth.
- Deficiency usually detected in newborns and hormone therapy given
- Deficiency inhibits full body growth
- Basal metabolic rate (BMR) can be used clinically to assess the status of thyroid function
- Deficiency causes slowed carbohydrate, lipid & protein metabolism. Excess causes opposite effect.
- Regulation of their own secretion
Hypothyroidism:
* Common or rare?
* Primary hypothyroidism is what?
- A common endocrine disorder. Affects about 1% of the adult population at some time.
- Primary hypothyroidism is most common and with low plasma concentrations of thyroid hormones but high levels of TSH due to a lack of negative feedback
Explain the pathways and levels in Primary and Secondary hypothyroidism
- Primary hyperthyroidism is characterized by what?
- Secondary hyperthyroidism has what?
- Primary hyperthyroidism is characterized by increased thyroid hormones and decreased TSH.
- Secondary hyperthyroidism has increased levels of both TSH and thyroid hormones
Explain the pathway and the levels of primary and secondary hyperthyroidism
- Hyperthyroidism increases what?
- Most common cause of excessive thyroid hormone production in humans is what? What forms?
- What are other causes of hyperthyroidism?
- Most common cause of excessive thyroid hormone production in humans is Graves disease, an autoimmune disorder caused by antibodies directed against the TSH receptor. Diffuse toxic goiter forms.
- Other causes - malfunctions of the hypothalamic–pituitary–thyroid axis.
- Hypothyroidism decreases what?
- What may result in a reduction in thyroid hormone production?
- Autoimmune diseases such as what impairs thyroid hormone synthesis?
- What are other causes of thyroid hormone deficiency include?
- Hypothyroidism decreases metabolism and causes weight gain.
- Iodide deficiency may result in a reduction in thyroid hormone production.
- Autoimmune diseases such as Hashimoto disease impair thyroid hormone synthesis.
- Other causes of thyroid hormone deficiency include heritable defects that alter the biosynthesis of thyroid hormones and hypothalamic or pituitary diseases that interfere with TRH or TSH secretion.
Characteristics of adrenal cortex+ their hormones:
* What is produced and secreted?
* Vascularized or no?
* How are hormones secreted?
* Long or short half life?
* Where do hormones bind?
- Adrenocorticoid production & secretion
- highly vascularized
- secrete on demand, do not store
- long half-lives in the body (hours)
- Bind to proteins (e.g. albumin) prevents mass excretion in urine
Fill in
- What are the three zones of the adrenal cortex? How much of the gland is cortex and medulla?
- Zona glomerulosa, fasciculata, reticularis
- Approximately 80% to 90% of the gland is the cortex, with 10% to 20% the medulla.
Trophic hormones act on their particular steroidogenic cells to increase what?
Trophic hormones act on their particular steroidogenic cells (e.g., ACTH→zona fasciculata, angiotensin II→zona glomerulosa) to increase expression of the steroidogenic acute regulatory protein (StAR), which translocates cholesterol from the outer to inner mitochondrial membrane.
YOU NEED STAR OR CANNOT MAKE CORTISOL
Fill in cortisol secretion
- Cortisol is secreted in response to what?
- In the absence of cortisol can be what?
Cortisol is secreted in response to virtually all forms of stress, including trauma, infection, illness, temperature change, and mental stress; in the absence of cortisol, even minor illnesses can be fatal
What are the major actions of cortisol (3)?
i. Anti-insulin metabolic effects to mobilize glucose and fatty acids.
ii. Maintain vascular responsiveness to pressor effect of catecholamines.
iii. Anti-inflammatory immune functions.
Metabolism of cortisol:
* Circulating cortisol is bound to what?
* Cortisol is metabolized by what?
- Circulating cortisol is ~90% bound to the corticosteroid-binding protein (transcortin) and a further 5% is bound to albumin.
- Cortisol is metabolized by the liver and kidney to 17-hydroxycorticosteroids, which are measured in 24- hour urine samples to assess cortisol secretion.
- Cortisol secretion has a circadian variation, with hormone levels highest when?
- The circadian rhythm of cortisol helps the body in what?
- In addition to the circadian rhythm, CRH is under the control of what?
- Cortisol secretion has a circadian variation, with hormone levels highest in the early morning hours
- The circadian rhythm of cortisol helps the body in
becoming active and alert in the morning and in reducing activity prior to sleep. - In addition to the circadian rhythm, CRH is under the
control of higher brain centers, demonstrated by peaks of CRH (and ACTH) release in response to stress.
- Aldosterone regulates what?
- How is Angiotensin II made? (figure)
Aldosterone regulates sodium and potassium to maintain fluid homeostasis
- Where is aldosterone is synthesized?
- The rate of renin secretion ultimately determines what?
- Aldosterone is synthesized in the cells of the zona glomerulosa.
- The rate of renin secretion ultimately determines the rate of aldosterone secretion
Fill in
Most cases of adrenocortical insufficiency (Addison’s disease) are due to what?
due to primary failure of the entire adrenal cortex (e.g., autoimmune adrenalitis, tuberculosis).
Cortisol deficiency results in what (3)
- fasting hypoglycemia due to low rates of hepatic gluconeogenesis
- hypotension due to lack of vascular responsiveness to pressor action of catecholamines;
- weakness and fatigue
Aldosterone deficiency further results in what (2)?
- hypovolemia and hyponatremia as a result of urinary losses of NaCl and water
- hyperkalemia and metabolic acidosis occur as a result of reduced urinary excretion of K+ and H+.
- Patients may become severely debilitated with adrenocortical insufficiency by what?
- Long-term glucocorticoid therapy for what?
- Patients may become severely debilitated by the inability to mount a response to stress and are then described as being in Addisonian crisis. (absence of cortisol)
- Long-term glucocorticoid therapy (e.g., rheumatoid arthritis) can suppress the hypothalamic-pituitary-adrenal axis through feedback inhibition. Adrenal insufficiency occurs if treatment is abruptly stopped. (need to tapper off)
What are symptoms of adrenocortical insufficiency?
Hypercortisolism (Cushing’s syndrome) is characterized by the following signs and symptoms (4)?
i. Hyperglycemia due to enhanced gluconeogenesis.
ii. Muscle wasting and weakness are due to protein catabolism.
iii. Truncal obesity and moon face caused by redistribution of body fat.
iv. Hypertension due to the mineralocorticoid effects of excess glucocorticoids
- The chromaffin cells of the adrenal medulla synthesize and secrete what?
- Catecholamines interact with what?
- Stimuli such as injury, anger, pain, cold, strenuous exercise, hypoglycemia, and psychological stress generate what?
- The chromaffin cells of the adrenal medulla synthesize and secrete the catecholamines epinephrine
and norepinephrine. - Catecholamines interact with four adrenergic receptors that mediate the cellular effects of the hormones.
- Stimuli such as injury, anger, pain, cold, strenuous exercise, hypoglycemia, and psychological stress generate impulses in the cholinergic preganglionic fibers innervating the chromaffin cells, resulting in the secretion of catecholamines.
- What is the rate limiting step of catecholamine synthesis?
- In sympathetic postganglionic neurons, the pathway ends with the production of what?
- The final conversion from norepinephrine to epinephrine only occurs where?
- Cortisol delivered via what?
- The release of catecholamines by the adrenal medulla is controlled by what?
- Chromaffin cells release what?
- Patients with pheochromocytoma, a secretory tumor of the adrenal medulla, do what and occurs?
What is the short term stress response?
What is the long term stress response?
- α -cells are mainly located where and secrete what?
- β -cells are mainly located where and secrete what?
- δ -cells secrete what?
- Blood flows through the islets of Langerhans from the center toward the periphery, to allow what?
- α -cells are mainly located at the periphery of the islets and secrete glucagon.
- β -cells are mainly located toward the center of the islets and secrete insulin, C peptide, and amylin.
- δ -cells secrete somatostatin.
- Blood flows through the islets of Langerhans from the center toward the periphery so that the α-cells receive a high concentration of insulin; insulin suppresses glucagon secretion
Insulin
- Insulin is cleaved from what?
- Urinary excretion of C peptide is a marker of what?
- The net effect of insulin on the plasma levels is what?
- The three major effector organs for insulin are what?
- Insulin is cleaved from the precursor proinsulin
- Urinary excretion of C peptide is a marker of insulin production because it is produced in a 1 to 1 ratio with insulin and is not degraded after secretion
- The net effect of insulin on the plasma levels is a reduction in glucose, amino acids, fatty acids, and ketoacids.
- The three major effector organs for insulin are the liver, skeletal muscle, and adipose tissue.
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- An independent rapid action of insulin is what?
- Insulin secretion after a meal is important to do what?
- Insulin is used therapeutically to treat what? Glucose is given at the same time to prevent what?
- An independent rapid action of insulin is increased cellular uptake of K+.
- Insulin secretion after a meal is important to quickly sequester ingested K+.
- Insulin is used therapeutically to treat hyperkalemia; glucose is given at the same time to prevent hypoglycemia and Ca 2+ is included to stabilize membrane potentials.
Glucose carbon is stored in the body in two primary forms, what are they?
Glycogen and triglycerides
- Explain how insulin stimulates glycogen synthesis and glucose metabolism (figure)
- Glycogen _ -term storage form
- Glycogen is Important role in maintaining what?
- Primary glycogen storage sites are where?
- Glycogen short-term storage form
- Important role in maintaining normal blood glucose levels.
- Primary glycogen storage sites are the liver and skeletal muscle
- Explain the effects of insulin on lipid metabolism in adipocytes (figure)
- In adipose tissue and the liver, insulin promotes and inhibits what?
- What else does Insulin inhibits what and how?
- Insulin increases the activity of what?
- In adipose tissue and the liver, insulin promotes lipogenesis and inhibits lipolysis
- Insulin inhibits the breakdown of triglycerides by inhibiting hormone-sensitive lipase
- Insulin increases the activity of lipoprotein lipase
Glucagon
- Similar to insulin, glucagon is first synthesized as part of what?
- What is the main target organ for glucagon?
- Similar to insulin, glucagon is first synthesized as part of a larger precursor protein.
- The main target organ for glucagon is the liver.
The main effects of glucagon opposing insulin actions are to what (3)?
i. Increase glucose production via glycogenolysis and gluconeogenesis.
ii. Increase lipolysis in adipose tissue via stimulation of hormone sensitive lipase.
iii. Increase hepatic ketone synthesis from fatty acids.
Control of glucagon secretion:
* Secretion is stimulated by what?
* Secretion is inhibited by what?
* Ingestion of a protein-rich meal stimulates what? Insulin increases what?
i. Secretion is stimulated by hypoglycemia, amino acids, vagal stimulation (acetylcholine), and by epinephrine (via β2 -adrenergic receptors).
ii. Secretion is inhibited by hyperglycemia, insulin, and somatostatin.
iii. Ingestion of a protein-rich meal stimulates both glucagon and insulin secretion. Insulin increases amino acid uptake while glucagon prevents the development of hypoglycemia
from increased insulin.
Glucagon promotes what? (2)
- Glucagon promotes hepatic glucose production, coupled with ammonia disposal
- Glucagon promotes the oxidation of fats and ketogenesis in the liver
Amylin:
* What is this?
* Synthesis is stimulated by what?
- Is a peptide hormone stored in β-cell granules with insulin and C-peptide.
- Synthesis is stimulated by increased plasma glucose and fatty acids
Amylin aids insulin action by decreasing spikes in blood glucose concentration by what (3)
- Slowing gastric emptying.
- Increasing satiety.
- Inhibiting glucagon secretion.
Amylin is the main constituent of what?
Amylin is the main constituent of amyloid that accumulates and injures β -cells in type 2 diabetes.
Somatostatin:
Secreted by what and in response to what?
Somatostatin is secreted by δ-cells in pancreatic islets in response to increased plasma nutrient levels.
The physiological effect of pancreatic somatostatin is unclear but somatostatin agonists are used pharmacologically to what (2)?
- Inhibit hormone secretion from tumors (e.g., insulinoma, glucagonoma, VIPoma, GH-secreting adenoma, etc.).
- Manage gastrointestinal bleeding via vasoconstriction of splanchnic vessels
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- Insulin resistance is an underlying aspect of what?
- Twice as many people have what?
- A1C (sometimes called hemoglobin A1C, HbA1C, or glycohemoglobin), measures what?
- What is insulin resistance?
- How is insulin resistance manifested by what?
- Insulin resistance is an underlying aspect of prediabetes, type 2 diabetes, and gestational diabetes.
- twice as many people have prediabetes
- A1C (sometimes called hemoglobin A1C, HbA1C, or glycohemoglobin), measures percent of glucose attached to hemoglobin
- insulin resistance - presence of an impaired biologic response to either exogenously administered or endogenously secreted insulin.
- manifested by decreased insulin-stimulated glucose transport and metabolism in adipose tissue and skeletal muscle and by impaired suppression of hepatic glucose output.
- What are the main hormones that regulate Ca 2+ and phosphate homeostasis?
- Ca2+ and phosphate balance are linked because why?
- Parathyroid hormone (PTH) and vitamin D (and Calcitonin to an extent) are the main hormones that regulate Ca 2+ and phosphate homeostasis.
- Ca2+ and phosphate balance are linked because they are both present in hydroxyapatite crystals in bone.
Ca2+ exists in three forms in plasma, list them
- 45% free ionized Ca 2+.
- 45% bound to plasma proteins (e.g. albumin).
- 10% complexed with anions
Phosphate occurs in two major forms in plasma, list them
- 80% alkaline phosphate (HPO 4 2−)
- 20% acid phosphate (H 2 PO 4−).
Plasma [phosphate] less strictly regulated than [Ca2]
Explain the normal daily Ca2+ balance and normal daily phosphate balance (figures)
- What are cells consitute the major cell types in bone?
- Explain the changes in bone calcium content as a function of age in males and females
- Osteoblasts (build up), osteocytes (bone cells), and osteoclasts (break down bone) constitute the major cell types in bone
- Osteoporosis leads to what?
- Rickets and osteomalacia are what?
- Paget disease is what?
- Osteoporosis leads to decreased bone density and increased risk of fracture
- Rickets and osteomalacia are disorders of defective bone mineralization
- Paget disease is a chronic disorder leading to enlarged and deformed bones
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- PTH, CT, and 1,25-(OH)2D3 together regulate plasma calcium and phosphate.
Long-term, hormonal regulation of plasma calcium and phosphate is under the control of waht?
PTH, calcitonin (CT), and vitamin D3.
Calcium
- Sequential hydroxylation reactions in the liver and kidneys convert vitamin D to what?
- This hormone stimulates what?
- Sequential hydroxylation reactions in the liver and kidneys convert vitamin D to the active hormone 1,25 dihydroxycholecalciferol.
- This hormone stimulates intestinal calcium absorption and, thereby, raises the plasma calcium concentration.
- What is calcitonin? What secretes calcitonin?
- Calcitonin opposes the effects of what?
- In humans, calcitonin has weak effects of what?
- Calcitonin is a peptide hormone secreted by the thyroid gland from parafollicular cells (thyroid C cells) in response to hypercalcemia.
- Calcitonin opposes the effects of PTH to reduce plasma Ca2+ by decreasing bone resorption by osteoclasts and increasing urinary Ca2+ excretion.
- In humans, calcitonin has weak effects of Ca 2+ homeostasis, and neither the absence nor the excess of calcitonin causes a clinical defect in Ca2+ or phosphate homeostasis.
