Hormones and Stress

Hormones and Stress

Hormones

Classifying Hormones by StructureSteroid Hormones

Fat-soluble chemical messenger synthesized from cholesterol

Examples: gonadal (sex) hormones, thyroidPeptide Hormones

Chemical messenger synthesized by cellular DNA that acts to affect the target cell’s physiology

Examples: insulin, growth hormone

Hormones

Classifying Hormones by FunctionHormones that maintain homeostasis

State of internal metabolic balance and regulation of physiological systems in an organism

Gonadal (sex) hormones Control reproductive functions and sexual appearance

and identity

Stress hormones (e.g., glucocorticoids) Secreted in times of stress (fight or flight); important in

protein and carbohydrate metabolism

HormonesHierarchical Control

Four LevelsHypothalamusPituitary GlandTarget Endocrine GlandsTarget Organs and Tissues

HormonesHierarchical Control

Hormones affect almost every neuron in the brain

Hormones Neurons Genes Proteins

HormonesHomeostatic Hormones

Homeostasis of intracellular and extracellular environments are essential to life

Diabetus mellitus Caused by a failure of the pancreas to secrete

enough (or any) insulin Hyperglycemia: High blood-glucose levels; cells

are not using glucose and therefore are not able to function properly

Hypoglycemia: Low blood-glucose levels

HormonesGonadal Hormones

Sex hormones begin to affect us before we are born and continue to affect us throughout our life

Organizational Hypothesis Proposal that actions of hormones during

development alter tissue differentiation Example: Testosterone masculinizes the brain

Biological effects of sex hormones

organizational effects: permanent structural changes elicited by sex hormones during critical period of embryonic / fetal life

activational effects: reversible effects of sex hormones (e.g. estrus)

Steroid Hormones Act Through Gene Expression

hormone

Hormone receptor

hormoneHormone receptor

Gene products

Synthesizes transcription factor

mRNA

HormonesGonadal Hormones

Sex hormones contribute to brain differences: Male brain is slightly larger than female after

correcting for body size Right hemisphere is larger than the left hemisphere

in men Female brains have higher rates of cerebral blood

flow and glucose utilization Parts of the corpus callosum are larger in women Language areas of the brain are somewhat larger in

women

Copyright © 2004 Allyn and Bacon

Neural Control of Sexual Behavior Brain Mechanisms

Sexually dimorphic nucleus (SDN): A nucleus in the preoptic area that is much larger in males

than in females; first observed in rats; plays a role in male sexual behavior.

Periaqueductal gray matter (PAG): The region of the midbrain that surrounds the cerebral

aqueduct; plays an essential role in various species-typical behaviors, including female sexual behavior.

Copyright © 2004 Allyn and Bacon

HormonesGonadal Hormones

Sex hormones contribute to differences in cognitive performance: Men tend to excel on spatial tasks whereas women

tend to excel on verbal tasks Performance of women differs during the course of

menstruation Low female sex hormones: Better spatial performance High female sex hormones: Better verbal performance

Differences between pre- and postmenopause, and during various stages of pregnancy

Gender differences in brain structure & function

less lateralization of cerebral hemispheres in women (in men, left more concerned with verbal skills, right with visual-spatial function)

larger fiber tracts in female corpus callosum “sexually dimorphic nucleus” present in hypothalamus

(also: INAH 3)

Males > FemalesFemales > Males

Difference in Solving Intellectual Problems

• Boys and girls different way of developing brains.

• Difference between boys and girls lies in patterns of ability rather than in overall level of intelligence (IQ).

***

Townsend et al. 2004

Hormonal Control of Sexual Behavior of Laboratory Animals Males

Oxytocin: A hormone secreted by the posterior pituitary gland; causes

contraction of the smooth muscle of the milk ducts, the uterus, and the male ejaculatory system.

Prolactin: A hormone of the anterior pituitary gland, necessary for

production of milk; has an inhibitory effect on male sexual behavior.

Copyright © 2004 Allyn and Bacon

Hormonal Control of Sexual Behavior Hormonal Control of Female

Reproductive Cycles

Corpus luteum: A cluster of cells that develops from

the ovarian follicle after ovulation; secretes estradiol and progesterone.

Progesterone: A steroid hormone produced by the

ovary that maintains the endometrial lining of the uterus during the later part of the menstrual cycle and during pregnancy.

Organizational Effects of Androgens on Behavior:Masculinization and Defeminization Effects of Pheromones

Pheromone: A chemical released by one animal that affects the behavior

or physiology of another animal; usually smelled or tasted.

Lee-Boot effect: The slowing and eventual cessation of estrous cycles in

groups of female animals that are housed together; caused by a pheromone in the animals urine.

Organizational Effects of Androgens on Behavior:Masculinization and Defeminization Effects of Pheromones

Whitten effect: The synchronization of the menstrual or estrous cycle of a

group of females, which occurs only in the presence of a pheromone in a male’s urine.

Vandenbergh effect: The earlier onset of puberty seen in female animals that are

housed with males; caused by a pheromone in the male’s urine.

HormonesStress HormonesStressor

A stimulus that challenges the body’s homeostasis and triggers arousal

Stress Response The physiological and behavioral arousal and any

attempt to reduce the stress Two sequences

Fast-acting: Activation of sympathetic nervous system; “fight-or-flight” response

Slow-acting: Activation of parasympathetic nervous system; “rest-and-digest” response

Stress Disorders

Stress: A general, imprecise term that can refer either to a stress

response or to a stressor (stressful situation).

Stressor: A stimulus (or situation) that produces a stress response.

Stress Disorders

Fight-or-flight response: A species-typical response preparatory to fighting or fleeing;

thought to be responsible for some of the deleterious effects

of stressful situations on health.

Stress Disorders Physiology of Stress

Glucocorticoid: One of a group of hormones of the adrenal cortex that are

important in protein and carbohydrate metabolism, secreted

especially in times of stress.

Stress Disorders Physiology of Stress

Corticotropin-releasing hormone (CRH): A hypothalamic hormone that stimulates the anterior

pituitary gland to secrete ACTH.

Adrenocorticotropic hormone (ACTH): A hormone released by the anterior pituitary gland in

response to CRH; stimulates the adrenal cortex to produce

glucocorticoids.

Copyright © 2004 Allyn and Bacon

CRF and the Hypothalamus

PVN

CRH

AnteriorPituitary

Glucocorticiods

AdrenalCTX

ACTH

Target Organs

PVN

CRH

AnteriorPituitary

Glucocorticiods

AdrenalCTX

ACTH

Systemic effects:

Fight or flight responses

↑BP ↑HR ↑O2 ↑Blood sugar

LH

Lateral horn

Adrenalmedulla

Epi/NE

Functions

BASAL LEVELS (Proactive)Circadian rhythmMoodSleepSensory perceptionLearning

ELAVATED LEVELS (Reactive)Stress Reponses

CRH Feedback

RapidpvnIntermediateCort (pvn/pituitary)DelayedHigher brain areas

PVN

CRH

AnteriorPituitary

Glucocorticiods

AdrenalCTX

ACTH

Hippocampus

CRH

CORT

SeptumBNST

Somatostatin

BRAKE

INHIBIT CRH

Release

Receptors

-

PVN

CRH

AnteriorPituitary

Glucocorticiods

AdrenalCTX

ACTH

CRF Receptor types

CRF Receptor types

TYPE 1 (MR) High affinity Binds CORT and

aldosterone Stabilizes excitability Stress Sensitivity

TYPE 2 (GR) Low affinity Binds only CORT Suppresses

excitability Recovery from stress

CRF receptor distribution

CRF cellular effects

CRF cellular effects

Chronic Stress

Both Receptors down regulatedEnlarged Adrenal glandReduced neuronal activityReduced neurogenesisReduced metabolic activityInhibited Glucose uptake

Chronic Stress and Hypothalamic integration

Stress and Depression Hypothesis

Depression is predicated by

deregulation of the HPA axis

PVN

CRH

AnteriorPituitary

Glucocorticiods

AdrenalCTX

ACTH

Hippocampus

CRH

CORT

SeptumBNST

Somatostatin

BRAKE

INHIBIT CRH

Release

Receptors

-

Stress and Depression Hypothesis

Stress and Depression Hypothesis

After depression treatment Cort secretion returns to normal

Cushing Disease- always depressed

High CORT and CRH disregulates 5ht, causing Learned Helplessness

Symptomology matches CRH functions

Dexamethasone Test

Stress and Depression Hypothesis

CRH/Depression leads to behavioral symptoms and inability to learn new coping strategies

Therapy or SSRI Drug treatment allows for the brake to become functional again

Prozac—BDNF ---ROS-neurogenesisTherapeutic lag = Mrna CORT rebalancing

PVN

CRH

AnteriorPituitary

Glucocorticiods

AdrenalCTX

ACTH

HippocampusAMYGDALA

NE

CORT Receptors

MemoryStorage

NE

Stress Disorders Psychoneuroimmunology

Psychoneuroimmunology: The branch of neuroscience involved with interactions

between environmental stimuli, the nervous system, and the immune system.

Antigen: A protein present on a microorganism that permits the

immune system to recognize the microorganism as an invader.

Stress Disorders Psychoneuroimmunology

Antibody: A protein produced by a cell of the immune system that

recognizes antigens present on invading microorganisms.

B-lymphocyte: A white blood cell that originates in the bone marrow; part of

the immune system.

Stress Disorders Psychoneuroimmunology

Immunoglobulin: An antibody released by B-lymphocytes that bind with

antigens and help to destroy invading microorganisms.

T-lymphocytes: A white blood cell that originates in the thymus gland; part of

the immune system.

Stress Disorders Psychoneuroimmunology

Cytokine: A category of chemicals released by certain white blood

cells when they detect the presence of an invading microorganism; causes other white blood cells to proliferate and mount an attack against the invader.

HormonesEnding a Stress Response

Normally, stress responses are briefStress responses are turned on and off in

the brainSapolsky (2003)

Hippocampus is involved in turning off the stress response

Too much cortisol will damage neurons in the hippocampus

Vicious cycle involving prolonged stress, cortisol levels, and hippocampal functioning

HormonesEnding a Stress Response

Posttraumatic Stress Disorder Syndrome characterized by physiological

arousal symptoms related to recurring memories and dreams related to a traumatic event – for months or years after the event