Dr. Michael P. Gillespie. Mediator Molecules in Nervous & Endocrine Systems The nervous system...

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Transcript of Dr. Michael P. Gillespie. Mediator Molecules in Nervous & Endocrine Systems The nervous system...

Dr. Michael P. Gillespie

Mediator Molecules in Nervous & Endocrine SystemsThe nervous system utilizes

neurotransmitters to control body functions.The endocrine system utilizes hormones to

control body functions.

Site Of Mediator Action In Nervous & Endocrine SystemsThe neurotransmitters perform their action

close to the site of release.The hormones usually perform their action

far from their site of release.

Types Of Target Cells In Nervous & Endocrine SystemsThe nervous system acts upon muscle cells

(smooth, cardiac, and skeletal), glands, and other neurons.

The endocrine system acts upon virtually all cells of the body.

Time To Onset Of Action In Nervous & Endocrine SystemsIn the nervous system, action typically occurs

within milliseconds of neurotransmitter release.

In the endocrine system, action can take seconds to days to occur after release of the hormone.

Duration Of Action In Nervous & Endocrine SystemsThe actions tend to be briefer in duration in

the nervous system and longer in duration in the endocrine system.

Comparison of Nervous and Endocrine System ControlCharacteristic Nervous System Endocrine System

Mediator Molecules Neurotransmitters – released locally

Hormones – delivered throughout the body by the blood

Site of Mediator Action

Close to site of release

Usually far from site of release

Types of target cells Muscle (smooth, cardiac, and skeletal) cells, gland cells, other neurons

Cells throughout the body

Time to onset of action

Within milliseconds Seconds – hours - days

Duration of Action Typically briefer (milliseconds)

Generally longer (seconds to days)

HormonesA hormone is a mediator molecule that is

released in one part of the body but regulates activity of cells in other parts of the body.

Most hormones enter the interstitial fluid and then the bloodstream.

Hormones travel through the bloodstream to cells throughout the body.

Several neurotransmitters are also hormones (i.e. norepinephrine).

Functions Of HormonesHelp regulate:

Chemical composition and volume of the internal environment (interstitial fluid).

Metabolism and energy balance.Contraction of smooth and cardiac muscle

fibers.Glandular secretions.Some immune system activities.

Functions Of HormonesControl growth and development.Regulate operation of reproductive systems.Help establish circadian rhythms.

“Supersystem”The nervous and endocrine systems function

together.Parts of the nervous system stimulate or

inhibit the release of hormones.Hormones can promote or inhibit the release

of nerve impulses.

Exocrine Glands Versus Endocrine GlandsExocrine glands (Exo = outside) – secrete

their products into ducts that carry secretions into body cavities, into the lumen of an organ, or to the outer surface of the body.

Endocrine glands – secrete their hormones into the interstitial fluid surrounding the secretory cells.

Exocrine Glands Versus Endocrine GlandsExocrine glands.

Sudoriferous (sweat).Sebaceous (oil).Mucous.Digestive.

Exocrine Glands Versus Endocrine GlandsEndocrine glands.

Pituitary.Thyroid.Parathyroid.Adrenal.Pineal.Other organs that secrete hormones:

Hypothalamus, thymus, pancreas, ovaries, testes, kidneys, stomach, liver, SI, skin, heart, adipose tissue, & placenta.

Endocrine SystemAll endocrine glands and hormone secreting

cells comprise the endocrine system.Endocrinology (-logy = study of) is the study

of the science of endocrine glands, function of endocrine glands, diagnosis of endocrine disorders and treatment of endocrine disorders.

Hormone ReceptorsHormones bind with specific receptors.Only target cells for a given hormone have

specific receptors that bind and recognize that hormone.

A target cell can have anywhere between 2000 and 100,000 receptors for a particular hormone.

Receptors are constantly being synthesized and broken down to meet the needs of the body.

Down-regulationIf a hormone is present in excess, the number

of target cell receptors may decrease.Down-regulation decreases the

responsiveness of the target cell to the hormone.

Up-regulationWhen a hormone (or neurotransmitter) is

deficient, the number of receptors may increase.

Up-regulation makes a target cell more receptive to a specific hormone.

Synthetic HormonesSynthetic hormones in the form of drugs can

block the receptors from naturally occurring hormones.

Circulating & Local HormonesCirculating hormones – pass from secretory

cells that make them into the interstitial fluid and then into the blood.Most hormones are of this type.

Local hormones – act locally on neighboring cells or on the same cells that secreted them without first entering the bloodstream.

Local HormonesParacrines – (para = beside or near) act on

neighboring cells.Autocrines – (auto – self) act on the same cell

that secreted them.

Local Hormones

Example Of A Local HormoneInterleukin 2 (IL-2) is an example of a local

hormone.It is released by helper T cells during immune

responses.It acts on nearby immune cells (paracrine) and

on itself (autocrine).This generates more helper T cells and boosts

the immune response.

Duration of Local Versus Circulating HormonesLocal hormones usually are inactivated

quickly.Circulating hormones linger longer.The liver eventually deactivates circulating

hormones and the kidneys excrete them.

Chemical Classes Of HormonesLipid-soluble hormones.

Steroid hormones.Thyroid hormones.Nitric oxide (NO).

Chemical Classes Of HormonesWater-soluble hormones.

Amine hormones.Peptide hormones and protein hormones.Eicosanoid hormones.

Prostaglandins. Leukotrienes.

Hormone Transport In BloodMost water-soluble hormones are transported

in their “free” form (not attached to plasma proteins).

Most lipid-soluble hormones are bound to transport proteins.

Hormone ReceptorsLipid-soluble hormones – the receptors are

located inside the target cells.Water-soluble hormones – the receptors are

located within the plasma membrane of the target cells.

Action Of Lipid-soluble HormonesLipid soluble hormones turn specific genes of

the nuclear DNA on or off.This directs the synthesis of a new protein

(often an enzyme).These new proteins alter the cells activity.

Action Of Water-soluble HormonesWater soluble hormones are the first

messenger. They activate the second messenger i.e. cyclic AMP (cAMP).

This initiates a cascade of events within the cell that produces millions of enzymes to catalyze reactions.

Phosphodiesterase inactivates cAMP.

Lipid Soluble Hormones

Water Soluble Hormones

Summary of Hormones By ClassRefer to Table 18.2

Responsiveness Of The Target CellThe responsiveness of the target cell depends

upon the following:The hormone’s concentration.The number of the hormone receptors on the

target cell.Influences exerted by other hormones.

Influences Of Other HormonesPermissive effect – the action of a 2nd

hormone is required for the 1st hormone to take effect.Thyroid hormones (2nd) allow epinephrine to

stimulate lipolysis.

Influences Of Other HormonesSynergistic effect – the sum of the actions

of the 2 hormones is greater than either hormone individually.Estrogens and FSH promote development of

oocytes.

Antagonistic effect – one hormone opposes the actions of another.Insulin promotes synthesis of glycogen and

glucagon stimulates breakdown of glycogen.

Control Of Hormonal SecretionHormone secretion is regulated by:

Signals from the nervous system.Chemical changes in the blood.Other hormones.

HypothalamusServes as a major integrating link between

the nervous system and the endocrine system.

Painful, stressful, and emotional experiences cause changes in hypothalamic activity.

Synthesizes at least 9 different hormones.Regulates the pituitary gland.

Pituitary Gland (hypophysis)Synthesizes at least 7 different hormones.Release of anterior pituitary hormones is

stimulated by releasing hormones and suppressed by inhibiting hormones from the hypothalamus.

Attaches to the hypothalamus by a stalk, the infundibulum (= a funnel).

Types Of Anterior Pituitary Cells & Their HormonesSomatotrophs – secretes human growth

hormone (hGH) or somatotropin, which stimulates tissues to secrete insulinlike growth factors (IGFs).

Thyrotrophs – secrete thyroid-stimulating hormone (TSH) or thyroptropin.

Types Of Anterior Pituitary Cells & Their HormonesGonadotrophs – secrete follicle-stimulating

hormone (FSH) and luteinizing hormone (LH) which act on the gonads.They stimulate the secretion of estrogen and

progesterone and the maturation of oocytes in the ovaries.

They stimulate the secretion of testosterone and sperm production in the testes.

Types Of Anterior Pituitary Cells & Their HormonesLactotrophs – secrete prolactin (PRL), which

initiates milk production.Corticotrophs – secrete adrenocorticotropic

hormone (ACTH) or corticotropin, which stimulates the adrenal cortex to secrete glucocorticoids.

Tropic Hormones (tropins)Hormones that influence another gland are

called tropic hormones or tropins.

Control Of Secretion By The Anterior Pituitary (adenohypophysis)The hypothalamus secretes five releasing

hormones and two inhibiting hormones.Negative feedback loops from hormones

released from target glands decrease the release from the anterior pituitary gland.

Human Growth Hormone & Insulinlike Growth FactorsThe main function of hGH is to promote

synthesis of IGFs.IGFs cause cells to grow and multiply.They help to maintain the mass of muscles

and bones.They promote healing of injuries and

tissue repair.They enhance lypolysis in adipose tissue.

Release Of hGHTwo hypothalamic hormones control the

release of hGH:Growth hormone releasing hormone (GHRH).

Stimulated by hypoglycemia. Inhibited by hyperglycemia.

Growth hormone inhibiting hormone (GHIH). Stimulated by hyperglycemia. Inhibited by hypoglycemia.

Thyroid-stimulating HormoneThyroid-stimulating hormone (TSH)

stimulates the synthesis and secretion of two thyroid hormones:Triiodothyronine (T3).

Thyroxine (T4).

Thyrotropin-releasing hormone (TRH) from the hypothalamus controls TSH secretion.

Negative feedback from T3 and T4 inhibits the release of TRH.

Follicle-stimulating HormoneFSH initiates the development of ovarian

follicles and stimulates follicular cells to secrete estrogens in females.

FSH stimulates sperm production in the testes in males.

Follicle-stimulating HormoneGonadotropin-releasing hormone (GnRH)

from the hypothalamus stimulates FSH release.

Estrogens in females and testosterone in males suppresses release of GnRH and FSH through negative feedback systems.

Luteinizing Hormone (LH)In females LH triggers ovulation.FSH and LH work together to stimulate the

release of estrogen.In males, LH stimulates the release of

testosterone from the testes.

Prolactin (PRL)Initiates and maintains secretion of milk by

the mammary glands.By itself, prolactin has only a weak effect.

Prolactin (PRL)Only with the effects of estrogens,

progesterone, glucocorticoids, hGH, thyroxine and insulin does PRL bring about milk.

The hypothalamus secretes both inhibitory and excitatory hormones that regulate PRL secretion:Prolactin-inhibiting hormone (PIH).Prolactin-releasing hormone (PRH).

Hypersecretion Of ProlactinIn males – erectile dysfunction.In females – galactorrhea (inappropriate

lactation) and amenorrhea (absence of menstrual cycles).

Adrenocorticotropic Hormone (ACTH)ACTH controls secretion of cortisol and

other glucocorticoids by the cortex of the adrenal gland.

Corticotropin-releasing hormone (CRH) from the hypothalamus stimulates secretion of ACTH.

Glucocorticoids cause inhibition of CRH and ACTH through negative feedback systems.

Principle Actions Of Anterior Pituitary HormonesTable 18.4 page 655.

Posterior Pituitary (neurohypophysis)The posteror pituitary does not synthesize

any hormones; however, it does store and release two hormones from the hypothalamus:Oxytocin (OT).Antidiuretic hormone (ADH) a.k.a. vasopressin.

OxytocinDuring delivery, oxytocin enhances

contraction of smooth muscle cells in the wall of the uterus.

After delivery, oxytocin stimulates milk ejection (“letdown”) from the mammary glands in response to the suckling infant.

Antidiuretic Hormone (ADH)ADH is a substance that decreases urine

production.ADH causes the kidneys to return more water

to the blood.

Summary Of Posterior Pituitary HormonesTable 18.5 page 658.

Thyroid GlandLocated inferior to the larynx (voice box).Right and left lateral lobes connected by

an isthmus.Anterior to the trachea.Highly vascular.Consists of thyroid follicles (spherical

sacs).The walls of each follicle contain follicular

cells, which extend into the lumen of the follicle.

Follicular CellsProduce two thyroid hormones (both are lipid

soluble).Thyroxine (tetraiodothyronine or T4).Triiodothyrronine (T3).

Parafollicular CellsAlso known as C cells.Produce the hormone calcitonin (CT).

Regulates calcium homeostasis.CT inhibits the action of osteoclasts.CT accelerates the uptake of calcium and

phosphates into the bone matrix.

Actions Of Thyroid HormonesIncrease basal metabolic rate (BMR).Stimulates synthesis of Na+ / K+ ATPaseCalorigenic effect.

Helps to regulate body temperature.Regulate metabolism.

Protein synthesis.Increase the use of glucose and fatty acids for

ATP.Increase lypolysis.

Actions Of Thyroid HormonesAccelerate body growth, especially of the

nervous system.Enhances actions of the catecholamines

(norepinephrine and epinephrine). In hyperthyroidism there is an increased heart rate, more forceful heartbeats, and increased blood pressure.

Parathyroid GlandsEmbedded into the posterior surface of the

lateral lobes of the thyroid gland.Superior and inferior parathyroid glands.Two kinds of epithelial cells.

Chief (principal) cells – produce parathyroid hormone (PTH) or parathormone.

Oxyphil cell – function unknown.

Parathyroid HormoneRegulates levels of calcium, magnesium, and

phosphate ions in the blood.PTH increases the activity and # of

osteoclasts.PTH stimulates the kidneys to synthesize

calcitrol (active form of vitamin D).Calcitrol stimulates increased absorption of

Ca2+ from the GI tract.

Adrenal GlandsThe paired adrenal (suprarenal) glands lie

superior to each kidney.Consists of the adrenal cortex (80-90% of the

gland) and the adrenal medulla.Highly vascularized.

Adrenal Gland HormonesAdrenal Cortex – steroid hormones.Adrenal Medulla – 3 catecholamine

hormones.Norepinephrine.Epinephrine.Dopamine.

Aldosterone (Cortex)Regulates homeostasis of sodium ions and

postassium ions.Promotes the secretion of H+ in the urine to

regulate acid-base balance. Prevents acidosis (pH below 7.35).

Renin-angiotensin-aldosterone (RAA) pathway controls the secretion of aldosterone (Controls blood pressure).

Glucocorticoids (Cortex)Regulate metabolism and resistance to

stress.Cortisol (hydrocortisone).Corticostrerone.Cortisone.

Low levels of glucocorticoids, mainly cortisol, stimulate the hypothalamus to secrete corticotropin-releasing hormone (CRH), which promotes the release of ACTH from the anterior pituitary, which in turn stimulates glucocorticoid secretion.

Effects Of GlucocorticoidsIncrease the rate of protein breakdown.Stimulates glucose formation by breaking

down glycogen stores and through gluconeogenesis.

Stimulates lypolysis.

Effects Of GlucocorticoidsResistance to stress by supplying ATP and

raising BP in cases of severe blood loss.Anti-inflammatory effects – inhibit WBCs

(also slows wound healing).Depression of immune responses (utilized

with organ transplant recipients).

Androgens (Cortex)The adrenal cortex secretes small

amounts of androgens (primarily dehydroepiandrosterone DHEA).

Assists in early growth of axillary and pubic hair in both sexes.

Contributes to libido and provides a source of estrogens after menopause in females.

ACTH stimulates its secretion.

Adrenal Medulla HormonesEpinephrine (adrenaline).Norepinephrine (noradrenaline).These two hormones augment the fight or

flight response.Increase the heart rate and force of

contraction.Dilates the airways in the lungs.Shunts blood to heart, liver, skeletal muscles,

and adipose tissue.Increases blood levels of glucose and fatty

acids.

Pancreatic IsletsBoth and endocrine and exocrine gland.Pancreatic islets (a.k.a. islets of Langerhans).4 major cell types:

Alpha (A) cells – secrete glucagon.Beta (B) cells – secrete insulin.Delta (D) cells – secretes somatostatin

(identical to growth hormone inhibiting hormone).

F cells – secrete pancreatic polypeptide.

Pancreatic HormonesGlucagon raises blood glucose levels.Insulin lowers blood glucose levels.Somatostatin inhibits both glocagon and

insulin release.Pancreatic polypeptide inhibits

somatostatin secretion, gallbladder contraction and secretion of digestive enzymes by the pancreas.

Regulation Of Glucagon & Insulin SecretionHypoglycemia stimulates release of glucagon.Glucagon causes hepatocytes to convert

glycogen to glucose (glycogenolysis).Hyperglycemia inhibit release of glucagon.

Regulation Of Glucagon & Insulin SecretionInsulin allows glucose to diffuse into cells,

increases amino acid uptake by cells, and increaes fatty acid uptake by cells.

This facilitates glucose conversion into glycogen (glycogenesis), synthesis of proteins, and synthesis of fatty acids (lipogenesis).

GonadsOvaries (female gonads).

Produce steroid hormones. Estrogens. Progesterone.

Produce inhibin.Produce relaxin.

Testes (male gonads).Produce testosterone (an androgen).Produce inhibin.

Females Sex HormonesEstrogen and progesterone along with FSH

and LH (from the anterior pituitary), regulate the menstrual cycle, maintain pregnancy, and prepare the mammary glands for lactation.

Maintain the feminine secondary sex characteristics (larger breasts and hips).

Inhibin & RelaxinInhibin inhibits secretion of FSH.Relaxin increases the flexibility of the pubic

symphisis during pregnancy and helps dilate the cervix during labor and delivery.

Male Sex Hormones (Androgens)Testosterone regulates the production of

sperm.Stimulates the production of male secondary

sex characteristics (beard growth and deepening of the voice).

Pineal GlandA small endocrine gland attached to the roof

of the third ventrical of the brain.Secretes melatonin.More melatonin is released in darkness.Melatonin contributes to the body’s biological

clock.

Seasonal Affective Disorder (SAD)Thought to be due to overproduction of

melatonin during the winter months.Full spectrum bright-light therapy can assist

with SAD and jet lag.

ThymusLocated behind the sternum between the

lungs.Hormones produced – thymosin, thymic

humoral factor (THF), thymic factor (TF), amd thymopoeietin.

Promotes the maturation of T cells and may retard the aging process.