Chapter 39

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Where do the nervous and endocrine systems coordinate together?
Hypothalamus
Define hormone.
A blood-borne chemical messenger that has an effect on target cells anatomically different from the secreting cell
Describe what paracrine means
Hormone is secreted by one cell and affects adjacent cells
Describe what autocrine means
Hormone is secreted by one cell and affects itself
Describe what neurocrine means
Secretion of hormones into the bloodstream by neurons
Ex. used in hypothalamic-pituitary communication
What functions do hormones regulate?
Reproduction, growth/development, fluid homeostasis, metabolism
What the chemical classes of hormones?
Water soluble
Lipid soluble
True or false: water-soluble hormones travel freely in plasma
True
True or false: water soluble hormones can cross the plasma membrane to a cell
False. They require a cell surface receptor
What are the types of water-soluble hormones?
Peptides
Tyrosine-derived catecholamines
What chemical stucture makes up the majority of endocrine hormones?
Peptides/polypeptides
How are lipid soluble hormones transported through the plasma?
Transport proteins (globulin)
Where are hormone transport proteins manufactured?
Liver
What is the general mechanism of action for lipid soluble hormones?
Detach from transport protein, cross cell membrane, activate intracellular receptors in cytoplasm or nucleus
What are the types of lipid soluble hormones?
Thyroid hormones
Steroids
Where do water-soluble hormones have a binding site on receptor cells?
External portion
What happens once a hormone with cell membrane receptors binds to a receptor?
Sends a signal to the interior of the cell
What is the second messenger?
Generated in response to first messenger
What is the first messenger?
Original hormone
What are the lipid soluble hormones?
Triiodothyronine (T3)
Thyroxine (T4)
Aldosterone
Cortisol
Corticosterone
Estrogen
Progesterone
Testosterone
Vitamin D
What is the most common type of hormone receptor?
G-protein linked receptor
What is a kinase?
Enzymes that attach phosphates (phosphorylation) to target proteins to change their activity and initiate signaling cascade
What is the usual target of cAMP in hormone signaling?
protein kinase A
What can activate the Gq pathway?
Norepinephrine and epinephrine
How to norepinephrine and epinephrine activate the Gq pathway?
Binding to alpha-1 receptors
For water soluble hormones, what are the types of hormone action?
G-protein linked receptors and protein kinase receptors
How do protein kinase receptors work?
When a hormone attaches to an external binding site, the kinase activates itself and become phosphorylated
What are phosphorylases?
Enzymes within a cell that remove the attached phosphates from the kinase
What is phosphorylation-dephosphorylation?
A strategy for controlling enzyme activity in cells
What happens when a hormone is dephosphorylated in a cell?
The enzyme is turned off
How does amplification of hormone activity work?
Each activated G-protein can interact with up to 100 or more target enzymes
True or false: lipid soluble hormones can show amplification cascade
False. Only water-soluble hormones can use the amplification cascade
True or false: steroid hormones can diffuse across the plasma membrane of cells
True.
True or false: Thyroid hormones can diffuse across the plasma membrane
False. This was thought to be the case for a long time. We now know that thyroid hormones use transport carriers
For hormones with intracellular receptors: where are the receptors located in the cell?
Cytoplasm or nucleus
How is gene expression changed with intracellular receptors?
Hormone-receptor complex binds to specific DNA binding sites
True or false: Lipid soluble hormone action is faster than water soluble hormone action
False
Where are most endocrine hormones manufactured?
Rough endoplasmic reticulum
What are most endocrine hormones stored?
Vesicles within cells
What is the form in which most hormones are stored?
Prohormone/pre-prohormone
Describe the synthesis of catecholamines.
1. Enzymes in the cytoplasm start with tyrosine
2. Convert tyrosine to dopamine
3. Stop at dopamine or
4. Convert dopamine to norepinephrine/epinephrine
How are water-soluble hormones stored in cells
Contained in vesicles by the lipid bilayer until triggered for release
True or false: steroid hormones are formed on demand
True
What are steroid hormones derived from?
Cholesterol
True or false: thyroid hormones are formed on demand
False. They are made ahead of time and stored until use
What protein are thyroid hormones bound to?
Thyroglobulin
True or false: All thyroid hormones must be bound to transport proteins for movement in the body
False. Most thyroid hormone is bound, however a very small percentage is free in the body.
The anterior pituitary secretes hormones based on what type of pattern?
Cyclical
What part of the brain regulates the cycles for hormone secretion
Hypothalamus
What is the most common type of feedback in hormone regulation?
Negative feedback
How are water soluble hormones excreted?
Urinary filtrate
What organs metabolize hormones?
Kidneys and liver
Where are lipid soluble hormones stored?
Adipose tissue
Which class of hormone remains in circulation longer?
Lipid soluble
True or false: pharmacologic hormone concentrations are much higher than physiologic hormone concentrations
True
A cell's ability to respond to a hormone depends on what?
The presence of specific receptors
How can target cells regulate their responsiveness?
Alter receptor number, affinity, and efficiency of coupling
What is specificity?
The molecular "fit" of a hormone to a receptor
What is affinity?
Degree of tightness of the hormone-receptor bond
What is cross-specificity?
Certain hormones can fit into the same shape receptor
What is receptor down-regulation?
Seen in cells exposed to high concentration of hormone.
Results in decrease in number of receptors
What is receptor up-regulation?
Response to chronically low hormone concentrations.
Increase in number of receptors.
What is permissiveness?
Hormones can increase the number of receptors for other hormones, thus enhancing the effect of the second hormone
What is a normal physiological process for permissiveness?
Allows cellular events to occur in sequence.
Ex: menstrual cycle
What is a hormone antagonist?
A blocking agent.
A chemical that binds to a receptor without initiating the typical intracellular changes.
What is a hormone agonist?
Binds hormone receptors and cause the same intracellular events that would occur with hormone-receptor binding
Where is the pituitary gland located?
Beneath the hypothalamus in the sella turcica
How is the pituitary gland connected to the hypothalamus?
Pituitary stalk
What is another name for the anterior pituitary gland?
Adenohypophysis
What is another name for the posterior pituitary gland?
Neurohypophysis
What is secreted from the posterior pituitary gland?
Antidiuretic hormone (vasopressin) and oxytocin
What hormones does the posterior pituitary produce?
None. ADH and oxytocin and produced in the hypothalamus
What stimulates the release of antidiuretic hormone (ADH)?
1. Osmoreceptors in the hypothalamus detects altered serum osmolality.
2. Baroreceptors sense hypovolemia and low arterial BP
Where does ADH target once released?
vasopressin 2 (V2) G-protein-linked receptors on the basolateral membrane of distal renal tubule
What nerves are directly related to the posterior pituitary gland?
Paraventricular and supraoptic nuclei
What is the function of ADH?
Causes water retention by increased water reabsorption by the renal collecting duct
How does ADH function?
Causes aquaporine to move from cytoplasm to the tubular cell membranes, allowing free diffusion of water from the tubular fluid into the cell
What is the result of ADH function?
1. Conserves water in the body
2. Creates concentrated urine
3. Reduces serum osmolality
True or false: oxytocin can inhibit diuresis
True. Oxytocin can do this because it is structurally similar to ADH
What stimulates the release of oxytocin?
1. Sexual activity
2. Childbirth--stretching of cervix
3. Breast-feeding--stim. of nipple and areola
What is the function of oxytocin?
Causes uterine and milk duct contractions
How does oxytocin function?
1. Oxytocin is released
2. It binds to myoepithelial cells surround the milk ducts
3. This causes contraction of the duct and ejection of milk
What type of feedback is exhibited by oxytocin?
Positive feedback loop
How are water soluble hormones excreted?
Urinary filtrate
What organs metabolize hormones?
Kidneys and liver
Where are lipid soluble hormones stored?
Adipose tissue
Which class of hormone remains in circulation longer?
Lipid soluble
What structures specifically modulate the pulsatile and circadian rhythm of hormone secretion?
Suprachiasmatic nucleus and pineal gland
What is the three-tiered axis?
The relationship between the hypothalamus and the anterior pituitary.

1. Hypothalamic releasing/inhibiting hormones
2. Anterior pituitary hormones
3. Target organ hormones
Describe the transport of hormones from the hypothalamus to the anterior pituitary.
1. Releasing/inhibiting factors secreted into hypothalamic capillary bed
2. Hypothalamic hormones diffuse into capillary network
3. Travel down portal vein
4. Diffuse from anterior pituitary capillary to the tissue
What is the hypothalamic and tropic hormone secreted from corticotrope cells?
Corticotropin-releasing hormone (CRH) and Adrenocorticotropic hormone (ACTH), respectively
What is the target endocrine gland for corticotropes?
Zona fasciculate and zona reticularis of adrenal cortex
What is the peripheral horomone involved in negative feedback of corticotropes?
Cortisol
What is the hypothalamic and tropic hormone secreted from thyrotrope cells?
Thyrotropin-releasing horomone (TRH) and Thyroid-stimulating horomone (TSH), respectively
What is the hypothalamic and tropic hormone secreted from gonadotrope cells?
Gonadotropin-releasing horomone (GnRH) and Follicle-stimulating hormone (FSH)/Luteinizing hormone (LH), respectively
What is the hypothalamic and tropic hormone secreted from somatotrope cells?
Growth hormone releasing hormone (GHRH)/ somatostatin (inhibitory) and Growth hormone (GH), respectively
What is the hypothalamic and tropic hormone secreted from lactotrope cells?
Dopamine (inhibitory)/prolactin-releasing factor (stimulatory) and Prolactin, respectively
What is the target endocrine gland for thyrotropes?
Thyroid epithelium
What is the target endocrine gland for gonadotropes?
Ovary and testis
What is the target endocrine gland for somatotropes?
Liver
What is the target endocrine gland for lacotropes?
None
What is the peripheral horomone involved in negative feedback of thyrotropes?
Triiodothronine (T3)
What is the peripheral horomone involved in negative feedback of gonadotropes?
Estrogen, progesterone, testosterone, inhibin
What is the peripheral horomone involved in negative feedback of somatotropes?
IGF-1
What is the peripheral horomone involved in negative feedback of lactotropes?
None
What hormone can have a positive and negative feedback effect?
Estrogen
What inhibits growth hormone?
Somatostatin
What type of pattern is growth hormone secreted in?
Circadian
When is GH secretion greatest during the day and during the lifetime?
Day: deep, slow-wave sleep
Lifetime: adolescence
What is the major target of GH? What are the lesser targets?
Liver.
Muscle and adipose tissue.
What are the effects of growth hormone?
1. Stimulates production of IGF-1
2. Increases muscle mass
3. Decreases fat mass by inducing lipolysis
What is IGF-1?
An anabolic hormone that increases growth of bone and cartilage tissues of body
What else can stimulate the release of IGF-1?
Insulin
How does growth hormone affect metabolic processes?
1. Increase rate of protein synthesis
2. Decrease protein catabolism
3. Slow carb utilization
4. Increase mobilization and use of fats
What stimulates the release of GH?
Hypoglycemia, increase in amino acids, starvation, and excercise
What cells does prolactin act on?
Numerous cell types
What is the function of prolactin?
Breast development, lactation, suppresses reproductive function
How does prolactin suppress fertility?
By suppressing GnRH (gonadotropin releasing hormone)
True or false: prolactin is normally inhibited
True.
What is another name for prolactin-inhibiting factor?
Dopamine
What can happen when a patient takes dopamine blockers?
Gynecomastia
Galactorrhea
What stimulates the release of prolactin?
Estrogen production, nipple stimulation, orgasm, stress, exercise
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