3. hormones

12 01neurLecture 4 ; Sept 17, 2013Hormones

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Current topics: nerve agents Many chemical weapons and

nerve gases kill by interfering with the neuromuscular junction.

The neuromuscular junction is a lot like a synapse, except it is found between motor neurons coming from the spinal cord and skeletal muscle fibers.

Acetylcholine (Ach) is the neurotransmitter used by the neuromuscular junction. When Ach is released at the

neuromuscular junction, the muscle fiber will contract. This is how we move.

Neuromuscular junctions on skeletal muscle.

Muscle fiber!

Neuromuscular junction!


Nerve agents Up close, the neuromuscular

junction looks similar to the synapses discussed earlier.

Like a synapse, after Ach is released it must be cleaned up and disposed of. This is accomplished by an enzyme called acetylcholinesterase.

Nerve agents like sarin, VX, and others permanently block acetylcholinesterase.

The result is a rapid build up of Ach at the neuromuscular junction. The muscles cannot relax, and the individual loses complete control of his/her body. Death occurs by suffocation you

need muscles to breath.

Nerve agent!

Acetylcholinesterase!

Muscle fiber!


Introduction to hormones Hormones are chemical messengers that are

secreted by glands that act on targets elsewhere in the body.

Contrast this with neurotransmitters, which are also chemical messengers. Hormones work over long distances, while neurotransmitters work over very small distances (i.e. the synaptic cleft.)

The endocrine system uses hormones secreted into the blood stream by specialized glands. Exocrine glands secrete substances outside of the

body. Examples include: sweat, tears, digestive secretions.

Endocrinology is the study of endocrine hormones and the eects they have on the brain and body.


History of endocrinology Humans have likely been indirectly

aware of certain endocrine hormones since pre-historic times.

The practice of castration (also called neutering in veterinary practice) involves removing the male testes. This produces an animal that is much more docile and easy to handle.

Though practice for millennia, nobody had ever really considered why the testes are needed for masculine behaviors.

Bull: Intact male cow. Strong, angry, and mean.

Ox: Castrated male cow. Strong, but quite friendly!


History of endocrinology In 1849, A.A. Berthold (1803-1861)

noted that removing the testes from a developing rooster caused it to become a docile capon. Capons lack many male-type behaviors and anatomical traits (they look more like hens).

Berthold found that if you put some other testes back into a capon, its male-type behaviors and anatomical traits would return.

Importantly, this worked even though Berthold did not re-connect the nerves. This suggested to him that the testes secreted a substance into the blood.

A.A. Berthold, rooster testicle expert.


History of endocrinology Somewhat later in history, Charles-

douard Brown-Squard (1817-1894) injected himself with a potion made from the testes of guinea pigs and dogs. According to him, this concoction gave

him youthful virility and energy.

All of this shows that there are substances (in this case testosterone) in the body that released into the blood by specific glands (in this case the testes) that have widespread eects on the body and behavior.

These substances are called hormones - to set in motion (G.).

Charles-douard Brown-Squard, first steroid user?

A guinea pig.


The endocrine system


Principles of hormone action1. All hormones act in a gradual fashion.

2. All hormones act by changing the probability of intensity of a behavior. They do not work like on/o switches.

3. The relationship between behavior and hormones is reciprocal. This means that hormones can change

behaviors, and behaviors can change hormone levels.

4. A hormone can have multiple eects on the body and brain. Similarly, one behavior can be affected by

several hormones.


Principles of hormone action5. Many hormones have a pulsatile secretion

pattern. They are released in bursts.

6. Levels of hormones change over time. Some may vary over the course of the day, others vary over across the month, and others the lifespan.

7. There are often interactions between dierent hormones that change their eects.

8. The structure of hormones are similar between species, but they often have dierent functions.

9. Only cells with receptors specific to a given hormone can be aected by that hormone.

Example: Growth Hormone (GH) is secreted in pulses over the 24h day. It varies over the lifespan teenagers have the highest levels (they are growing, after all).


Hormonal vs. neural signaling

Synaptic or neurocrine function involves chemical release and diusion across a synaptic cleft.

Endocrine function involves hormones being released into the bloodstream to act on target tissues.


Hormonal vs. neural signaling Hormonal communication is similar to neural

communication in three basic ways:

1. Neurons and endocrine glands produce and store chemicals (neurotransmitters or hormones) and release them upon stimulation.

2. Neurotransmitters and hormones both bind to receptors to stimulate target cells.

3. Some chemicals can act as either hormones or neurotransmitters, depending on where they are released. For example: norepinephrine is a

neurotransmitter associated with alertness in the CNS, but it is also a hormone released by the adrenal glands under conditions of stress or anxiety.

Norepinephrine (NE) is produced in the locus coeruleus of the pons and acts as a neurotransmitter in the brain.

Norepinephrine (NE) is also produced by the adrenal glands where it travels through the body as a hormone.


Hormonal vs. neural signaling Hormonal communication is dierent from neural

communication in five basic ways:

1. Neural signals travel to precise destinations. Hormones spread everywhere and are picked up by cells with the proper receptor.

2. Neural signals are rapid (measured in ms). Hormonal signals are slower (measured in seconds and minutes).

3. Hormones travel great distances through the blood. Neurotransmitters travel very small distances across the synaptic cleft.

4. Neural signals are digital - all or nothing. Hormonal signals are analog graded in strength.

5. Neural signals are sometimes voluntary, while hormonal signals are always involuntary.


Other forms of communication

Pheromones - to carry (G.) are hormones used to communicate between members of the same species.

Allomones other (G.) are hormones used to communicate between members of dierent species.


Insulin

Major classes of hormones There are three families of hormones. These are

classified based on their chemical composition, not necessarily their function.

1. Peptide hormones are made of a string of amino acids, much like other proteins in our bodies (peptides are short proteins). Eg. Corticotrophin Releasing Hormone (CRH), Leptin.

Insulin.

2. Monoamine hormones are made of modified amino acids they are often found in the brain as neurotransmitters as well. Eg. Norepinephrine, Epinephrine (aka Adrenaline).

3. Steroid hormones are synthesized from cholesterol and have a four ringed structure. Eg. Cortisol, Estradiol, Testosterone.

Norepinephrine

Testosterone


Eects of hormones on cells Unlike many neurotransmitter receptors,

hormone receptors are not ion channels.

Rather than directly depolarizing the cell, when hormones bind to their receptors they trigger the release of intracellular second messengers.

These second messengers spread throughout the cell and cause a variety of physiological changes. Changes in metabolism, hormone release,

receptor trafficking, cell growth, etc.

Second messenger mediated eects are rapid.


Eects of hormones on cells Because they are lipophilic,

steroid hormones easily pass through the cell membrane and bind to receptors inside the cell.

The steroid-receptor complex binds to DNA and acts as a transcription factor controlling gene expression.

Transcription factor mediated mechanisms are slow, however their eects are long-lasting.


Eects of hormones on organs Hormones act throughout the body in many

ways. These can be generalized into three basic categories:

1. Hormones may promote proliferation, growth and dierentiation of cells. Example: Growth hormone promotes growth of the

long bones (during childhood and adolescence).2. Hormones may modulate cell activity and

metabolism. Example: Insulin increases glucose uptake by

muscle, fat, and liver. Example: Thyroid hormones increase glucose and

fat metabolism in all tissue.3. Hormones may modulate hormone secretion

from endocrine glands. Example: ACTH causes the release of cortisol from

the adrenal glands. Example: Negative feedback.

IGF-1GH


Control of hormone release The pituitary gland mucus, phlegm

(L.) is the master gland of the body, secreting hormones that aect function of glands and organs throughout the entire body.

The pituitary gland is located at the base of the brain and connected to the hypothalamus to by the pituitary stalk.

There are two parts of the pituitary gland: Anterior pituitary: connected to the

hypothalamus by blood vessels. Posterior pituitary: directly connected to

the hypothalamus by axons extending from hypothalamic neurons.


Anterior pituitary

Posterior pituitary

Control of hormone release The hypothalamus regulates

hormone secretion from the anterior and posterior pituitary. However, these two divisions function dierently.

The anterior pituitary receives releasing hormones from nuclei in the hypothalamus. These hormones stimulate the release of other hormones from the anterior pituitary.

The posterior pituitary receives axons from nuclei in the hypothalamus, these axons secrete hormones directly into circulation.


Anterior pituitary

Posterior pituitary

The anterior pituitary There are three steps involved in

glandular activity involving the anterior pituitary.

1. Releasing hormones from

hypothalamus travel a short distance through circulation to endocrine cells in the anterior pituitary.

2. Endocrine cells release a second

hormone into systemic circulation where it aects the body.


The anterior pituitary Most anterior pituitary hormones are

themselves releasing hormones for other glands in the body.

3. Anterior pituitary hormones travel through general circulation and reach their target gland (in this example the adrenal gland). The target gland secretes a third hormone that travels throughout the body and ultimately exerts a physiological eect.

Many glands in the body are therefore under hierarchical control, with the following chain of command: Hypothalamus > Anterior pituitary > Target

gland

Adrenal gland


Anterior pituitary

Posterior pituitary

The poster pituitary One step in posterior pituitary

hormone release:

1. Neuroendocrine neurons in the hypothalamus send axons to the posterior pituitary, where they release hormones into systemic circulation.

These hormones are able to act directly on the body, without needing to target second and third order intermediate glands.


Anterior vs. posterior pituitaryAnterior pituitary hormones:

Growth hormone (GH)

Stimulates growth of long bones, fat metabolism.

Thyroid-stimulating hormone (TSH) Stimulates the thyroid gland to

produce thyroid hormones that go on to increase metabolism.

Adrenocorticotropic hormone (ACTH) Stimulates the adrenal glands to

produce cortisol. Involved in the stress response.

Prolactin (Prl) Stimulates milk production (in

females). Luteinizing hormone (LH) and

Follicle-stimulating hormone (FSH) Stimulate the release of sex steroids

from gonads. Involved in the menstrual cycle (in females).

Posterior pituitary hormones:

Oxytocin (OT)

Stimulates birth, maternal behavior, social bonding.

Vasopressin (VP) Increases blood pressure, reduces

urine output. Also involved in pair bonding and social behavior.


Regulation of hormone secretion The endocrine system is capable

of self-regulation. The various hormonal systems use negative feedback to control their function.

The principle of negative feedback loops is critical in maintaining homeostasis.

Broadly speaking, negative feedback is the counteraction or reduction of an eect that occurs as a result of the eect itself.

James Watts centrifugal governor. A model of negative feedback for the mechanically inclined.


An example negative feedback loop

Hypothalamus!

High

Low

Hormone level in blood!

Set point

The hypothalamus determines a set point for the hormone level. In this case, the set point is a medium level of the hormone.

1. The hypothalamus detects circulating hormone levels. If they too low, the hypothalamus orders the secretion of more of that hormone.

2. The blood level of the hormone goes up.

3. At a certain point, the hormone levels approach (or slightly overshoot) the set point. In response, the hypothalamus orders hormone secretion to stop.

4. Hormone levels begin to decline again. The system loops back to step 1.

Pituitary gland!



Hypothalamus!

High

Low


Set point





4. Hormone levels begin to decline again. The system loops back to step 1, and the cycle repeats.

Pituitary gland!



Hypothalamus!

Pituitary gland!

High

Low


Medium





4. Hormone levels begin to decline again. The system loops back to step 1, and the cycle repeats.

A huge number of processes in the brain are governed by negative feedback loops. Real-world applications of this concept often involve several extra steps, but the basic process remains the same.

We will frequently return to the concept of negative feedback.


Lights, camera, action potentials!

http://www.youtube.com/watch?v=XdCrZm_JAp0

3. hormones

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