Lecture 1 (endocrine)-EXAM 5 Flashcards

Question

hormone regulation usually occurs via what

Answer 1

The mechanism is usually negative feedback, although a few positive feedback are known

Answer 2

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).

Answer 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 disorde**r is an excess or deficiency of secretion by the hypothalamus

Answer 4

Amines are kinda in the middle of peptide and steriod

Answer 5

Cat: peptides Thyroid: steroids

Answer 6

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+)

Answer 7

* 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

Answer 8

* 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

Answer 9

* 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+

Answer 10

i. Metabolism. ii. Binding in the tissues. iii. Hepatic excretion. iv. Renal excretion.

Answer 11

Plasma hormone concentration

Answer 12

* **Only free hormone is biologically activ**e – 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.

Answer 13

*** 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.

Answer 14

* 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.

Answer 15

* 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)

Answer 16

* 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)

Answer 17

* 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

Answer 18

* 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. ## Footnote Dose–response curves determine changes in responsiveness and sensitivity.

Answer 19

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.

Answer 20

* an alteration in receptor affinity or, if submaximal concentrations of hormone are present * a change in receptor number.

Answer 21

Up-regulation may occur when certain conditions or treatments cause an increase in receptor number compared with normal, or if receptor number has declined.

Answer 22

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 ## Footnote Example: giving exogenous hormones

Answer 23

* 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**.

Answer 24

Anterior pituitary hormones are **synthesized and secreted** in response to hypothalamic-releasing hormones carried in the hypophyseal portal circulculation

Answer 25

Magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus, whose axons terminate in the posterior lobe, synthesize posterior pituitary hormones.

Answer 26

synthesized in neurons located in the hypothalamic **paraventricular and supraoptic nuclei** from the **precursor peptides** prepropressophysin and preprooxyphysin, respectively.

Answer 27

ADH and oxytocin are secreted into the systemic blood from axon terminals in the posterior pituitary gland.

Answer 28

* **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

Answer 29

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

Answer 30

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

Answer 31

* Hypothalamic neurohormones control the release of anterior pituitary hormones and are delivered via the hypophyseal portal blood supply. * Optic chiasm

Answer 32

* **Somatotropes** secrete GH. * **Thyrotropes** secrete TSH. * **Corticotropes** secrete ACTH. * **Gonadotropes** secrete both LH and FSH * **Lactotropes** secrete prolactin.

Answer 33

* **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)

Answer 34

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

Answer 35

* 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

Answer 36

* 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

Answer 37

* 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

Answer 38

* 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**

Answer 39

* **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)

Answer 40

* **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

Answer 41

* 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**

Answer 42

* **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.

Answer 43

noncovalently bound (not too strong) to **thyroxine- binding globulin (TBG)**

Answer 44

* 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

Answer 45

* Anterior pituitary * Dietary iodide

Answer 46

* 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.

Answer 47

nuclear receptors expressed in all body tissues,

Answer 48

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.**

Answer 49

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

Answer 50

* 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

Answer 51

* 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**

Answer 52

* **Primary hyperthyroidism** is characterized by increased thyroid hormones and decreased TSH. * **Secondary hyperthyroidism** has increased levels of both TSH and thyroid hormones

Answer 53

* 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.

Answer 54

* **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.

Answer 55

* 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

Answer 56

* Zona glomerulosa, fasciculata, reticularis * Approximately 80% to 90% of the gland is the cortex, with 10% to 20% the medulla.

Answer 57

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. ## Footnote YOU NEED STAR OR CANNOT MAKE CORTISOL

Answer 58

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

Answer 59

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**.

Answer 60

* 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.

Answer 61

* 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**.

Answer 62

Aldosterone regulates sodium and potassium to maintain fluid homeostasis

Answer 63

* Aldosterone is synthesized in the cells of the zona glomerulosa. * The **rate of renin** secretion ultimately determines the **rate of aldosterone secretion**

Answer 64

due to primary failure of the entire adrenal cortex (e.g., autoimmune adrenalitis, tuberculosis).

Answer 65

* **fasting hypoglycemia** due to low rates of hepatic gluconeogenesis * **hypotension** due to lack of vascular responsiveness to pressor action of catecholamines; * **weakness and fatigue**

Answer 66

* **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+.

Answer 67

* 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)

Answer 68

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

Answer 69

* 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.

Answer 70

* **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

Answer 71

* 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.**

Answer 72

* 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.

Answer 73

Glycogen and triglycerides

Answer 74

* Glycogen short-term storage form * Important role in maintaining normal blood glucose levels. * Primary glycogen storage sites are the liver and skeletal muscle

Answer 75

* 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

Answer 76

* Similar to insulin, glucagon is first synthesized as part of a larger precursor protein. * The main target organ for glucagon is the liver.

Answer 77

i. **Increase glucose production** via glycogenolysis and gluconeogenesis. ii. **Increase lipolysi**s in adipose tissue via stimulation of hormone sensitive lipase. iii. Increase hepatic **ketone synthesis** from fatty acids.

Answer 78

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.

Answer 79

* Glucagon promotes hepatic glucose production, coupled with ammonia disposal * Glucagon promotes the oxidation of fats and ketogenesis in the liver

Answer 80

* Is a peptide hormone stored in β-cell granules with insulin and C-peptide. * Synthesis is **stimulated by increased plasma glucose and fatty acids**

Answer 81

* Slowing gastric emptying. * Increasing satiety. * Inhibiting glucagon secretion.

Answer 82

Amylin is the main constituent of amyloid that accumulates and injures β -cells in **type 2 diabetes**.

Answer 83

Somatostatin is secreted by δ-cells in pancreatic islets in response to increased plasma nutrient levels.

Answer 84

* **Inhibit hormone secretion** from tumors (e.g., insulinoma, glucagonoma, VIPoma, GH-secreting adenoma, etc.). * Manage gastrointestinal bleeding via **vasoconstriction of splanchnic vessels**

Answer 85

* **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.**

Answer 86

* 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.

Answer 87

* 45% free ionized Ca 2+. * 45% bound to plasma proteins (e.g. albumin). * 10% complexed with anions

Answer 88

* 80% alkaline phosphate (HPO 4 2−) * 20% acid phosphate (H 2 PO 4−). | Plasma [phosphate] less strictly regulated than [Ca2]

Answer 89

* Osteoblasts (build up), osteocytes (bone cells), and osteoclasts (break down bone) constitute the major cell types in bone

Answer 90

* **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**

Answer 91

* PTH, CT, and 1,25-(OH)2D3 together regulate plasma calcium and phosphate.

Answer 92

PTH, calcitonin (CT), and vitamin D3.

Answer 93

* 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.**

Answer 94

* 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.