Introduction to Hormones Flashcards
1
Q
Definition of Hormone
A
- “a chemical substance released by a cell that affects the activity of itself (autocrine), a neighboring cell (paracrine) or a distant cell (endocrine)”.
- This definition encompasses neurotransmitters, growth factors and traditional hormones.
2
Q
The direct point at which the nervous system and endocrine systems interface involves […], which are special types of neurons capable of secreting humoral secretions (hormones) in response to synaptic input (neurotransmitters).
A
The direct point at which the nervous system and endocrine systems interface involves ‘neuroendocrine’ cells, which are special types of neurons capable of secreting humoral secretions (hormones) in response to synaptic input (neurotransmitters).
•A comparison of the endocrine system with the nervous system suggests that a neuroendocrine event shares similarity with a paracrine event, in which neighboring cells provide input, as well as similarity with an endocrine event, in which the secretory output can be transported by the blood to a distant target organ.
3
Q
The major human hormone producing glands…
A
- adenohypophysis
- neurohpophysis
- thyroid and parathyroid glands
- teh adrenals
- the gonads
- the pancreas
- Certain other tissues such as the placenta, the hypothalamus, parts of the kidney and gastrointestinal tract, the liver and probably the pineal, thymus, and spleen also secrete hormones of primary importance.
- Endocrine glands are responsible for hormone synthesis, storage, and secretion.
4
Q
Chemical Classifications of Hormones
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- amino acid derivatives
- peptides and proteins
- steroid derivatives
5
Q
Amino Acid Derivatives
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6
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Peptide/Proteins
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7
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Steroid
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8
Q
Hydrophobic Hormones
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•Group I Hormones
- thyroid hormones
- itamin D
- steroids
9
Q
Hydrophilic Hormones
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•Group II Hormones
- peptides and proteins
- catelcholamines
10
Q
Tropic Hormones
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- A tropic hormone is secreted by one endocrine gland with a primary function being the regulation of another endocrine gland.
- The secretion of the tropic hormone is generally under the regulation of the hormone from the gland it regulates.
- For example, adrenocorticotropic hormone (ACTH) is secreted by the anterior pituitary to signal the formation in the adrenal cortex of cortisol.
- Excess circulating cortisol suppresses the formation and secretion of ACTH.
11
Q
Non-tropic Hormones
A
- Non-tropic hormones are hormones that directly stimulate target cells to induce effects.
- This differs from the tropic hormones, which act on another endocrine gland.
- Non-tropic hormones are those that act directly on targeted tissues or cells, and not on other endocrine gland to stimulate release of other hormones.
12
Q
A
13
Q
Factors Affecting Circulating Hormone Concentration
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- rate of secretion from the endocrine gland
- rate of metabolism
- method of transport
- concentration at any given time
14
Q
2 Major Functions of Serum Binding Proteins
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1) solubilize the hormone for transport in the blood,
2) extend the life of the hormone in circulation by protecting the small molecules from enzymatic degradation in the blood stream.
- Many of these serum-binding proteins are specialized in that they will bind only certain hormones.
- Conversely, albumin binds virtually all hydrophobic hormones.
15
Q
Specific Serum Binding Proteins vs. Albumin
A
- The affinity of the binding protein for hormone is greater for the specific serum binding proteins than for albumin.
- However, albumin is present in the plasma in far greater concentrations than the specific proteins, and therefore, has a greater capacity for binding and transporting hormones.
- The extent to which a hormone is protein bound varies from one hormone to another.
- In all cases, the total hormone pool is predominantly in the bound form; in some cases, only 1 per cent or less of the total hormone remains unbound, though there are exceptions.
- This distribution of hormone in the circulation is important because only the pool of free hormone is biologically active.
- The hormone (H) bound to the binding protein (BP) is in dynamic equilibrium with the free pool, which in turn is in equilibrium with the hormone bound to target tissues.
- Hormone that remains bound to plasma proteins cannot interact with its receptor and is biologically inactive.
•Binding proteins provide a large hormone reserve.
-The magnitude of the free hormone concentration, rather than the total concentration of hormone, is monitored and adjusted to maintain normal endocrine function.
16
Q
Measurement of Circulating Hormones
A
•body fluid
-urine or blood usually
•bioassays
- The measurement of hormone concentration in blood proved to be difficult since most hormones are present in extremely low amounts.
- These assays involve the ability to measure a sensitive biologic response in the whole animal (e.g. blood pressure, body growth) or in tissues (e.g. rate of oxygen consumption, target tissue weight) that is affected by the hormone and relatively specific for it. The bioassay can still be a valuable tool for determining the availability of bioactive hormone.
- More sensitive chemical analyses were developed to measure hormone concentrations.
- This approach is still extremely useful for estimating metabolites derived from the degradation of hormones such as thyroid hormones, steroids and catecholamines, especially in urine samples.
•More Sensitive Tests
- RIA
- ELISA
17
Q
RIA
A
- Because both radiolabeled and unlabeled hormone compete for antibody-binding sites in the serum, allowed the development of the radioimmunoassay (RIA) method.
- This method permits measurement of as little as 10-12 molar quantities of a specific hormone in the presence of a several billion-fold higher concentration of other proteins and peptides in the blood.
18
Q
ELISA
A
- The principle of RIA served as the basis for developing the enzymelinked immunoassay (ELISA) method.
- ELISA is the basis for home tests (e.g., home pregnancy test) where use of radioactivity is impractical.
- Instead of measuring bound radiolabeled hormone, the hormone binds first to an antibody-enzyme complex.
- Then the hormone bound to the antibody-enzyme binds to a second antibody containing a dye that is activated by the enzyme
19
Q
Measurement of Clearance Rate
A
- Inject bolus trace amount of labeled hormone
- Collect timed blood samples
- Measure radioactivity in sample
- Unlabeled [hormone] ~constant over time period due to secretion
- Labeled [hormone] decreases due to metabolism without replacement
- Rate of disappearance of labeled hormone approximates clearance of native hormone
20
Q
Classification of Hormones by Receptor Properties
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21
Q
Common Properties of Hormone Receptors
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- Protein in structure
- Bind hormone with high affinity
- Concentrate hormone within target cell
- Initiate a chain of events upon binding leading to biological response
- Dynamic in number and respond to physiological and biochemical cues
22
Q
A
23
Q
Endocrinopathies
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- Hyposecretion
- Hypersecretion
- Resistance
- Ectopic Tumor
24
Q
Endocrinopathies - Hyposecretion
A
- When hyposecretion occurs due to an endocrine gland secreting too little hormone due to an abnormality within that organ it is referred to as primary hyposecretion.
- Conversely, if the organ functions normally but is secreting too little hormone simply because it receives too little of its tropic hormone regulator, the condition is called secondary hyposecretion.
- Many different factors may act singly or in combination to cause hyposecretion.
- The most common treatment for hyposecretion disorders is administering the hormone in replacement therapy. Such replacement is straightforward in theory, but practical problems may be encountered associated with it regarding the source and means of administration.
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Endocrinopathies - Hypersecretion
* Hypersecretion by a particular organ is designated as primary or secondary depending upon whether the defect occurs within that organ or due to excessive stimulation from outside.
* A variety of conditions can produce hypersecretions
* Substance abuse is not caused by hypersecretion by an endocrine organ, but rather is an excess exogenous source of the hormone or its analog.
* When an endocrine tumor is present, it is often removed surgically or destroyed by radiation treatment.
-This approach is often followed with exogenous hormone replacement therapy.
* Hypersecretion can also be limited in some instances by medications that block hormone synthesis or inhibit hormone secretion.
* Finally, some hypersecretory conditions can be treated without actually reducing hormone secretion, but by giving antagonists that inhibit activation of the hormone receptor on its target tissue
26
Endocrinopathies - Resistance
* End organ insensitivity or resistance results in reduced responsiveness of the target tissue to hormone.
* In this case, adequate or even excessive amounts of hormone are being secreted, but the target tissues are unable to respond due to a congenital lack of receptors, or by a deficiency in the intracellular response mechanism of the target cell to that hormone.
* One of the most common examples is type 2 diabetes mellitus.
* Generally disorders in end organ responsiveness are the most difficult to treat, since simple manipulation of hormone amounts does not address the problem.
27
Endocrinopathies - Ectopic Tumors
* Ectopic tumors lead to endocrine disorders that do not reflect a direct disruption of the physiological endocrine system, but which mimic hypersecretion.
* Ectopic tumors secrete large amounts of a hormone that ordinarily would not be secreted by the tissue harboring the tumor.
* Consequently, this type of tumor is not subject to normal control mechanisms.
* The target tissue perceives it as such and responds appropriately.
* Malignant tumors of the lung are well known for overproducing protein hormones, such as ACTH.
* A patient may originally seek help in response to the symptoms that are produced by overabundance of the hormone.
28
Hierarchy of the Neuroendocrine System
•The nervous system is essentially “hard wired” and is faster than the endocrine system.
Both the nervous and endocrine systems evolved by exploiting primitive chemical messengers.
•Interaction of the nervous and endocrine systems forms a complex hierarchy, which is organized according to the sympathetic and central nervous systems
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Hypothalamic Releasing Hormones
•Regulation of release mediated by:
- neurotransmitters
- target gland hormones (feedback regulation)
- pituitary peptide hormones
- neuropeptide modulators
30
GHRH
•Pituitary Hormone:
- GH
- somatotrophs
- 50%
•Inhibitory Substance:
-GHIH
31
TRH
•Pituitary Hormone:
- PRL
- lactotrophs
- 10-20%
•Inhibitory Substance:
-PRIH (dopamine)
32
CRH
•Pituitary Hormone:
- ACTH
- corticotrophs
- 15-20%
•Inhibitory Substance:
-cortisol (from adrenal cortex)
33
TRH
•Pituitary Hormone:
- TSH
- thryotrophs
- 5%
•Inhibitory Substance:
-somatostatin
34
GnRH
•Pituitary Hormone:
- LH/FSH
- gonadotrophs
- 50%
•Inhibitory Substance:
- testosterone, inhibin (males)
- estradiol [E2], (females)
35
Endocrine Patterns of Rhythmicity
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Notable exceptions to the concept that most hormones appear to be at least in part under CNS control:
* Dependence of GI hormones on feeding
* Control of insulin release by blood glucose
* Control of parathyroid hormone, vitamin D and calcitonin by blood calcium concentration
* Modulation of blood pressure by both atrial peptides and renin-angiotensin- aldosterone system
37
Feedback Mechanisms
* Superimposed on endogenous rhythms of hormone release are a number of feedback mechanisms.
* The rate of hormone secretion by any endocrine organ can be varied, and as it varies, result in changes in hormone concentration in the blood.
* To maintain appropriate homeostasis, the endocrine organ must sense the systemic hormone concentrations, or some function of it.
* This awareness is provided in endocrine systems in the form of feedback loops.
* Basically, a hormonal feedback loop can be depicted as a system in which one substance affects the function of a second, and the response of that second substance feeds back to regulate the first.
* There are two major levels of feedback loops, the long loop such that the product of a distant target organ signals back to the CNS, hypothalamus or pituitary, and the short loop such that a product of the pituitary signals back to the hypothalamus.
38
Negative Feedback
* Negative feedback is by far the most common type of loop and is generally employed in maintaining homeostasis.
* The hypothalamic hormones can be integrated into a "big picture" that reiterates how each hypothalamic hormone affects its target cell in the anterior pituitary.
* While not a classic peptide inhibiting hormone, hypothalamic dopamine is a tonic suppressor (indicated by dashed arrow) of prolactin (PRL) secretion from the lactotrope.
-Gonadal estrogen (E2; estradiol) enhances PRL synthesis and release.
•Other long feedback loops include:
1) corticosteroids inhibiting release of ACTH, which stimulates the adrenal cortex to synthesize and release cortisol
2) thyroxine (T4) decreasing the release of TSH
3) IGF-1 diminishing the production and release of growth hormone
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* The general principle of coordinated CNS and peripheral actions of hormones has been documented in some cases for humans but most of the findings have been gleaned from rodent studies.
* Both vasopressin and oxytocin act on the CNS to induce specific behaviors.
- Oxytocin elicits “maternal behavior” in female rats when injected into the brain, indicating that in addition to its peripheral effects, it also has central actions.
- The central effects of oxytocin to elicit maternal behavior are logical and coordinate with the classic systemic roles of this hormone in parturition and nursing.
- In the case of vasopressin, intranasal administration evokes enhanced memory and learning in well-controlled human experiments. This effect would not seem to correlate with water retention and increased blood pressure, but one can argue that this CNS action of vasopressin provided an important evolutionary advantage by helping the animal to remember what situation led to life threatening blood loss or dehydration and avoid it in the future.
* For GnRH, the behavioral influence on mating behavior correlates with the release of LH and FSH, whose functions are associated with follicle growth (FSH), spermatogenesis (FSH), ovulation (LH) and sex steroid production (LH).
* In previous lectures, we studied the role of CCK in digestion of proteins and lipids in terms of secretion of pancreatic digestive enzymes and gall bladder contraction, and through the CNS, CCK affects satiety to curb food intake.
