WEEK9&10- Endocrine System

GLANDS

1. hypothalamus - production of ADH, oxytocin, regulating hormones

2. pituitary gland - anterior lobe, posterior lobe

3. thyroid- T3,T4, calcitonin

4. parathyroid - prathyroid hormone

5. thymus -thymusin, undergoes atrophy during adult hood

6. pineal gland - melatonin

7. heart - naturetic peptides

8. digestive tract - gastrin, secretin, somatostatin, CCK, GIP, VIP

9. adrenal gland -adrenal cortex(aldosterone,glucorticoid,sex hormone), adrenal medulla(adr,noradr)

10. pancreas - glucagon, insulin

11. kidney - erythropoietin, calcitriol

12. gonads- testis, ovaries

13. adipose tissue - leptin

 

 

 

 

 

HPT axis - hypothalamus pituitary thyroid axis

: regulates everything related to your homeostasis

 

RAA axis - renin angiontensin aldosterone axis

: regulates sodium/ potassium/ water balance

 

HPA axis - hypothalamus pituitary  adrenal axis

: complex series of interactions between three glands that ultimately regulates lots of your daily process (like digestion, sexuality, immune respond, and how you handle stress)

 

 

 

 

 

 

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TYPE of Horomones

1. Amino acid derivatice

2. peptide horomones

3. lipid derivative

 

water-soluble hormones act on receptors in the plasma membrane. coupled with regulatory G proteins

(peptide hormones + most amino acid derivative hormones bind to receptors on the plasma membrane)

Lipid-soluble hormones act on receptors inside the cell. directly activate genes

(Thyroid hormone and steroid hormones cross the plasma membrane and bind to receptors in the cytoplasm)

 

 

 

Hormone action

 

(Water-soluble hormones) -> act via intracellular second messenger system

1. hormone binds to receptors in the plasma membrane (1st messenger)

2. activates G protein

3. activates effector enzyme adenylate cyclase

4. converts ATP to cAMP (2nd messanger)

5. cAMP activates protein kinase

 

 

(Lipid-soluble hormones) -> act on receptors inside the cell to activate genes

1. steroid hormones and thyroid hormone diffuse into target cell, bind with intracellular receptor

2. Receptor-hormone complex enters nucleus and binds to DNA, specific region

3. transcription of DNA to produce mRNA

4.mRNA directs protein synthesis

 

 

 

 

 

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Horomone is secreted by 

1. Humoral stimulus - trigger hormone release in response to changing blood levels of certain critical ions or nutrients

2. neural stimulus - trigger hormone release in response to neural input

3. hormonal stimulus - hormones timulate release of other hormones

 

 

 

Hormone affects..

1. alter plasma membrane permeability

2. stimulate synthesis of enzymes

3. activates/deactivates enzymes

4. iduces secretory activity

5. stimulates mitosis

 

 

 

 

 

 

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Tropic vs Nontropic

Tropic hormones stimulste release of glandular hormones downstream

(ex) Thyroid stimulating hormone (TSH from anterior pituitary stimulates thyroid gland to secrete thyroxin)

 

Non-tropic hormones

Directly affect non-endocrine target tissues

(ex) PRL targets breast tissue and promotes lactation

GH affects metabolism (however GH actions on liver and bone growth are tropic effects)

 

 

 

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HYPOTHALAMUS

regulates..

1. autonomic nervous system

2. emotions

3. feeding/ satiety

4. thirst

5. body temperature

6. blood pressure

7. circadian rhythms

8. sleep

 

 

-Hypothalamic neurons synthesize releasing and inhibiting hormones to adrenohyphophysis (anterior pituitary gland)

: GHRH, GHIH -> GH / TRH -> TSH / CRH-> ACTH / GnRH -> FSH, LH / PIH-> PRL

 

 

 

 

 

 

 

 

 

 

PITUITARY GLAND

sits in the sella turcica of the sphenoid bone

 

 

* ANTERIOR (ADRENOHYPOHYSIS)

: endocrine tissue

: vascular connection with hypothalamus  (no neural contact)

: hypothalamic- hypophyseal portal system

 

-Portal system consists of 

1. Primary capillary plexus

2. Hypophyseal portal veins

3. Secontady capillary plexus

( vascular portal system is an unsual arrangement of blood vessels where two capillary beds are connected by veins)

 

1. When appropriately stimulated, hypothalamic neurons secrete releasing and inhibiting hormones into the primary capillary plexus

2. Hypothalamix hormones travels through portal veins to the anterior pituitary where they stimulate or inhibit release of hormones made in the anterior pituitary

3. In response to releasing hormones, the anterior pituitary secretes hormones into the secondary capillary plexus, this in turn empties into the general circulation

 

 

- GH : growth hormone  (Tropic and nontropic)

(regulated by GHRH, GHIH of hypothalamic hormones)

(regulated by blood glucose, free fatty acids, sleep, stress, thyroid hormone, glucocorticoids, sex steroids)

Tropic : GH stimulates  Liver and other tussues to produce IGFs(Insulin-like growth factors)
-> Increased cartilage formation and skeletal growth/ increased protein synthesis and cell growth.

Nontropic : metanolic anti-insulin
-> Increased fat breakdown and release/ Increased bood glucose and other anti-insulin effects

Hypersecretion
: Gigantism (before epiphyseal plate closed -> normal body portion)
: Acromegaly (after puberty/epiphyseal plate closed -> thichkening of bone but not elongation)

Hyposecretion
: Pituitary dwarfism

 

 

- TSH : thyroid stimulating hormone (thyroid gland) (Tropic)

(regulated by thyrotropin releasing hormone TRH of hypothalamic hormones)

(negative feedback from rising the blood levels)

 

 

- ACTH : adreno-corticotropic hormone (adrenal cortex) (Tropic)

(regulated by corticotropin releasing hormone CRH of hypothalamic hormones)

(regulated by other internal external factors such as fever, hypoclycaemia, and stressors)

(stimulate adrenal gland to secrete corticosteroids)

(glucocorticoids help body resist stress)

(cortisol is most significant in humans)

 

 

- FSH, LH : follicle stimulating hormone luteinizing hormone (testis and ovaries) (Tropic)

(regulated by gonadotropin releasing hormone GnRH)

(absent in puberty)

(FSH : stimulate gamate production)

(LH : maturation of the ovarian follicle, promotes synthesis of oestrogen and progesterone)

 

 

- PRL : prolactin (milk production) (Nontropic)

 

 

 

*POSTERIOR (NEUROHYPOPHYSIS)

: neural tissue

: neural connection with hypothalamus

:hypothalamic-hypophyseal tract 

 

1. Hypothalamic neurons synthesize oxytocin or antidiuretic hormone (ADH)

2. Oxytocin and ADH are transported down the axons of the hypothalamic- hypophyseal tract to the posterior pituitary

3. Oxytocin and ADH are stored in axon terminals in the posterior pituitary

4. When associated hypothalamic neurons fire, action potentials arriving at the axon terminals cause oxytocin or ADH to be released into the blood

 

- secretes ADH

: influences water balance, blood pressure, and the osmolarity of body fluids

: stimulated by low blood pressure or high plasma osmolarity

1. osmoreceptors in the hypothalamus monitor ECF osmolarity and Na+ concentration in plasma
2. hypothalamus stimulates posterior pituitary gland to secrete ADH // baroreceptors in atria and large vessels detect decrease in plasma volume and blood pressure
3. ADH targets collecting ducts of kidneys
4. increased water reabsorption 
5. results in decrease in ECF osmolarity and increase in plasma volume

 

- secretes oxytocin 

: stimulates smooth muscle contraction in breasts and uterus 

: stimulated by labour, or a baby sucking the breast 

-> child birth and milk letdown 

 

- The number of oxytocin receptors in the uterus peaks near the end of pregnancy
As uterus and cervix stretches closer to birth, affernt inpulses are sent to the hypothalamus, and oxytocin is released
- Stimulation of mechanoreceptors in nipples by suckling infant sends afferent impulses to the hypothalamus

 

 

Anterior lobe of pituitary gland

TSH (thyroid stimulating hormone)	thyroid gland	regulated by TRH
ACTH  (adrenocorticotropic hormone)	adrenal gland	CRH
Gonadotropins (FSH: follicle sitmulating hormone, LH: luteinizinf hormone)	testis and ovary	GnRH, GnIH
GH (growth hormone)	muscular and skeletal system	GRH, GIH
PRL (prolactin)	breast

 

 

 

 

 

 

 

THYROID GLAND

: largest endocrine gland

: located in anterior neck, naterior surface of the tracheam inferior to larynx

: composed of follicles which produce and store the glycoprotein thyroglobulin (the precursor of thyroid horone)

(walls of the follicles are made of squamous epithelial cells called follicular cells)

(Thyroid hormone overview) - effects of TH are crucial, wide, and varied

-The major metabolic hormone

-affect almost every cell in the body except spleen, testes, uterus, thyroid gland itself

-increase lipolysis( breakdown of stored lipids in adipocytes to release fatty acids for energy production)

-thermogenic (calorigenic-production of heat)

-increase the number of adregenic receptors in blood vessels and SNS activity 

-> heart rate, cardiac contractility increase and maintenance of blood pressure

-regulates tissue growth and development of skeletal and nervous system

-permissive for growth hormone (growth hormone can only exert its full effect because of the existence of thyroid hormone)

-works synergistically with reproductive hormones, prolactin

 

T4 : thyroxine
(two tyrosine molecules + four bound iodine atoms)
T3 : triiodothyronine
(two tyrosines + three bound iodine atoms)

-> they are lipid soluble
-> T3 is 10x more active than T4
-> peripheral tissues convert T4->T3 by moving one iodine

 

Thyroid hormone synthesis

1. TSH secreted by anterior pituitary binds to follicle cell receptors
2. leads to the formation and storage of thyroglobulin
3. Iodine trapping: iodine actively pumped from plasma into follicle cells and diffuses into center of follicle
4. Iodine is linked to thyroglobulin 
5. produce T4and T3 (two version of thyroid hormone)

-TSH secreted by anterior pituitary binds to follicle cell receptors
-leads to the formation and storage of thyroglobulin
-Iodine trapping : iodine actively pumped from plasma into follicle cells and diffuses into center of follicle
-Iodine is linked to thyroglobulin
-cleaves to produce T4and T3 (two version of TH)

 

 

 

Regulation of thyroid hormone 

- increased metabolic rate is required (ex: pregnancy, stress,cold in infants, thyrotropin-releasing hormone TRH is released from the hypothalamus)
- TRH stimulates the release of TSH from the anterior pituitary
- TSH stimulates thyroid hormone synthesis and release
- regulation of thyroid hormone is by negative feedback exerted by thyroid hormone on the anterior pituitary
-(negative feedback: increased thyroid hormone in the blood induces decrease in TSH secretion, negative feedback by increased thyroid hormone also acts on the hypothalamus to decrease TRH secretion)

 

 

 

 

DISORDERS

 

-Hypothyroidism : deficiency of thyroid hormones

(adults: myxoedema / children: cretinism)

: caused by iodine deficiency/ damage to the thyroid gland/ surgical removal of the thyroid

: decreased metabolic rate, weight gain, puffy skin, coarse hair, easily fatigued, lethargic, slow reflexes,constipation

 

 

-Hyperthyroidism/ Thyrotoxicosis : excess thyroid hormones

: weight loss, nervousness, sweating, metabolic rate, fine tremors

(Graves' disease : autoimmune antibodies activate the TSH receptor on follicle cells)

 

-Goitre : enlarged thyroid gland

: may accompanying either hyper of hypothyroidism

: most common cause is iodine deficiency

(TSH increases, but insufficient iodine makes follicles to just accumulate)

 

 

 

 

 

 

 

 

PARATHYROID GLAND

-parathyroid chief cells synthesize and secrete parathyroid hormone (PTH)

-PTH most important hormone regulating calcium balance in the blood  CALCIUM HOMEOSTASIS

(Ca2+ functions : transmission of nerve impulse, muscle contraction, blood clotting)

 

 

 

Effects of PTH 

 

1. stimulates osteoclasts to digest bone matrix releasing calcium and phosphate

2. inhibits osteoblasts

3. enhances the reabsorption of Ca2+ by the kidneys

4. increases secretion of phosphate by the kidneys

5. promotes activation of vitamin D

(which increases absorbtion of Ca2+ by intestinal mucosa)

6. regulated by negative feedback (rising Ca2+ in the blood inhibits PTH release)

 

 

 

 

 

 

 

 

 

 

 

 

 

Hyperparathyrodism : exces PTH

-increased blood calcium

-decreased bone mass

-> bone soften and deform as fibrous

-> connective tissue replaces mineral salts

 

 

* Calcitonin : hormone produced by the parafollicular cells (C cells) in thyroid gland (not in parathyroid)

-calcium homeostasis

-lower blood calcium level

-antagonist to parathyroid hormone (PTH)

: inhibits osteoclast activity

: decrease bone resorption

: decreases calcium release from bone matrix

: stimulates calcium uptake and incorporation into the bone matrix by osteoblasts

HOWEVER CALCIUM BALANCE is mainly regulated by PTH not Calcitonin

 

 

 

 

 

ADRENAL GLAND

Overall help us cope us with stress

-attached to the superior surface of the kidneys

-enclosed in a fibrous capsule and a cushion of fat

-structurally and funcitonally two glands in one

: medulla (neural tissue) 

: cortex (glandular tissue)

 

 

ADRENAL MEDULLA
- derived from neural tissue ( sympathetic nervous system )

- secretes hormones ( not neurotransmitters )

- adrenaline and noradrenaline 

 

ADRENAL CORTEX

-synthesis and secretion of steroid hormones (corticosteroids)

: Zona glomerulosa - mineralcorticoids - Aldosterone

: Zona fasiculata - glucocorticoids - Glucocorticoids

: Zona reticularis - sexhormones - Androgens

-All corticosteroids are lipid soluble as they are all synthesised from cholesterol

-They difuse through the lipid bilayer and use intracellular receptors

-Steroid hormones not stored in cells 

 

(Mineralcorticoids)

-Aldosterone : most potent mineralocorticoid

stimulated by 
1. rising blood levels of K+
2. The renin angiotensin aldosterone system (RAAS)
-> involved in increasing blood pressure

inhibited by 
Atrial natriuretic peptide (ANP) (released from the heart when blood pressure rises)
: inhibits release of aldosterone
: inhibits secretion of renin 
-> decrease in Blood pressure

-> regulates electrolytes in extracellular fluids (Na+ and K+)
: maintain Na+ balance by reducing urinary excretion of Na+
-> stimulates reabsorption of Na+ by the kidney
: plasma Na+ concentration affects ECF volume, blood volume, blood pressure
-> stimulates urinary K+ secretion
: hyperkalemia is life threatening ( K+ concentration sets the RMP of all cells and determines how easily an action potential may be generated in nerve and muscle)
(plasma electrolyte balance is precisely controlled and modified every 20 min)

 

(Glucocorticoids)

-Cortisol : magor glucocorticoids

-energy metabolism

-help resist stress (when stress increase, cortisol increases to negotiate the crisis)

-keeps blood sugar levels relatively constant by formation of new glucose in the liver (gluconeogenesis)

-increases release of glucose stores as glycogen

-stimulates breakdown of proteins -> amino acids (can generate new glucose)

-stimulates release of stored fatty acids from adipose cells (for same reason)

 

1. Corticotropin-releasing hormone (CRH) is released by the hypothalamus in a daily rhythym
(normally level peaks in the early morning)

2. CRH stimulates release of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland

3. ACTH stimulates cortisol secretion from the adrenal gland

4. release is increased in response to physical and emotional stress and hypoglycaemia 

5. negative feedback controls secretion

(Gonadocorticoids)

-Androgens : most adrenal gonadocorticoids are weak androgens

-> most convert to testosterone (some to oestrogens) in body tissues

-insignificant amounts from adrenal cortex reticularis cells compared with gonads (puberty)

-Afrenal androgens 

: onset of puberty, growth spurt in males

: appearance of secondary sex characteristics

: female sex drive

: maintenance of pubic and axillary hair

 

 

ADRENAL MEDULLA

-modified sympathetic neurons synthesize catecholamines adrenaline and noradrenaline

-> secretion strongly stimulated by sympathetic nerves to the adrenal medulla

-Adrenaline 

: 80% stored, ready for use when need, esp for flight and fight mode

: potent stimulator of increased blood flow to heart and skeletal muscle

: bronchodilation ( the airways in the lungs open up to allow greater air entry for oxygen delivery to these working muscles)

-Noradrenaline

:20% stored, increases peripheral vasoconstriction (increases pressure)

 

 

 

 

 

 

PINEAL GLAND

-indirectly recieves input from the retina via the visual pathways

-small gland hanging from the roof of the third ventricle of the diencephalon

-secretes melatonin

( melatonin induces phsiological processes that maintain rhythmic circadian variations)

( ex. body temperature, sleep, appetite )

-synthetic supplements used as a treatment for insomnia and jetleg

-Suprachiasmatic nucleus (in hypothalamus) inhibits melatonin release in daylight

-Paraventicular nucleus (in hypothalamus) stimulates pineal gland to release melatonin via neurons in upper spine and neck in dark

 

 

 

 

 

 

PANCREAS

-located in the epigastric and left hypochondriac regions

(posterior to the inferior part of the stomach, superior to the large intestine)

-posses both exocrine and endocrine cells

(Acinar cells : produce an enzyme-rich pancreatic juice used for digestion- exocrine product)

(Pancreatic islet : islets of Langerhans produce hormones - endocrine product)

Glucagon (a cell)

-increases blood glucose

-activity in liver

-release is triggered by fasting

 

Insulin (b cell)

-decreases blood glucose

-release is triggered by eating

 

Somatostatin (GHIH) (Delta cell)

-inhibits release of growth hormone and intestinal hormones

 

Pancreatic polypeptide (F cell)

-part of a family of hormones which regulate gut function and appetite

 

 

Diabetes mellitus (DM)

: blood glucose levels remain high after eating as glucose cannot enter cells

-Hyperglycaemia : nauseous, fright and flight response

-Glycosuria : sugar in urine

-cardinal signs of DM

: Polyuria, excessive volumes urine

(glucose is an osmotic diuretic so when there's glucose in the urine, water follows glucose!)

: Polydipsia, excess thirst

:Polyphagia, excess hunger (because body tissue cannot use glucose in the blood)

-Type 1 
: hyposecretion of insulin, damaged beta cells in pancreas

-Type 2
: hypoactivity of insulin, increased insulin resistance

 

 

 

 

 

 

GONADS

Testes : Testosterone 

-initiates maturation of male reproductive organs

-causes appearance of secondary sexual characteristics

-increases sex drive

-necessary for sperm production

-maintains sex organs in their functional state

-deeper voice

-growth of Adam's apple

 

 

Ovaries : oestrogen and progesterone

-maturation of the reproductive organs

-appearance of secondary sexual characteristics

-breast development

-cyclic changes in the uterine mucosa

-maintenance of vaginal mucosa

-maintenance of bone

 

 

 

 

 

 

 

 

 

 

 

 

 

ADIPOSE CELLS

Leptin

-appitite suppressant and stimulates increased energy expenditure

-adipose tissue also secretes hormones involved in energy metabolism

-abnormalities are often seen in diabetes

(the more fat stored, the more leptin is circulating in the blood stream)

 

 

 

 

 

 

THYMUS

-lobulated gland located deep to the sternum in the anterior mediastinum

-produces hormones essential for the development of the T lymphocytes (Tcells) of the immune system

-Once Tcell maturation is complete, thymus is vestigal in adults (Only important in children)

 

 

 

 

 

 

GASTROINTESTINAL TRACTS 

-Gastrin, cholecytokinin, secretin,..

-locally-acting digestive hormones (peptides) produced by enteroendocrine cells

 

 

 

 

 

 

 

 

PLACENTA

Human choronic gonadotropin (hCG)

-influences the course of pregnancy

-essential to maintain corpus luteum progesterone production in the first 3months of pregnancy

-promotes placental development

(Temporary endocrine organ)

 

 

 

 

HEART

Atrial natriuretic peptide (ANP)

- reduces blood sodium concentration -> blood volume decreases and blood pressure decreases

- inhibits renin release to same effect

 

 

 

 

 

 

 

 

 

KIDNEYS

Erythropoietin (EPO)

: signals to the bone marrows to increase red blood cell production

: also secretes renin (RAAS)

 

-calcitriol : Calcitriol acts on cells in the gastrointestinal tract to increase the production of calcium transport proteins, termed calbindin-D proteins, which results in increased uptake of calcium from the gut into the body.

-renin : associated with aldosterone release