Physiological Actions – Normal Stress Response:

Metabolic Effects- peripheral protein

, hepatic

Increased blood glucose concentration, lipolysis in

Enhanced effects of glucagon and

Mineralocorticoid effects

Renal and Cardiovascular Effects:

excretion of

vascular permeability

Other effects: Bone growth and CNS effects

Pharmacological effects of large amounts of cortisol:

Anti-inflammatory action, immunosuppressive action, anti-allergic action

All of these are associated with decreased production of molecules such as prostaglandins, leukotrienes, histamine, etc. as well as on the movement and function of leukocytes and the production of

Cortisol Receptors: Two receptors will bind to cortisol with equal affinity:

and aldosterone receptors

-aldosterone also binds to this receptor, therefore since two hormones bind to the same receptor, there is the potential of excessive receptor activity

To prevent excess mineralocorticoid receptor activation in the kidney, bioactive cortisol is converted to inactive

Mechanism of action: Similar to aldosterone, cortisol binds to

and the complex is transported to the nucleus where it binds to DNA stimulating protein synthesis

and annexin I receptor are synthesised

The annexin 1 then exhibits

action, preventing synthesis of

via arachidonic acid

Control of Cortisol:

Principally via

Released from the

Precursor is POMC, the control hormones are corticotrophin-releasing hormone and

released by the hypothalamus, which control the release of corticotrophin

Stimulation:

via brain nerve pathway and circadium rhythm (biological clock) stimulate the release of CRH and vasopressin from the hypothalamus, therefore increasing

Inhibition: The release of corticotrophin from the anterior pituitary gland has a short

feedback loop with the hypothalamus, inhibiting CRH and vasopressin release

Direct negative feedback to the

pituitary, inhibiting cortiocotrophin release

Indirect negative feedback to the

inhibiting CRH and vasopressin release

De-hydro-epi-androsterone (DHEA):

Precursor for androgens and

Converted to active hormones

target cells. Peak serum levels at 20-30 years, then decrease steadily with increasing age

Particularly important in

women as precursor for oestrogen (and androgen) synthesis by target tissues in the absence of ovarian steroids

Endocrine diseases- Syndromes of excess/deficiency of

Adrenal failure =

Excess cortisol =

Both adrenals have many

but only one

Spleen is at risk with a left

Micro anatomy: Look at John Laycock's lecture

Hormones: 3 classes- peptides, steroids and

Cholesterol:

carbon compound

Basic cyclic structure 17C, Side chain 8C

Most basic steroid hormone, as just involves removal of part of the cholesterol side chain-

This can then be oxidised, hydroxylated etc to form mineralocorticoids e.g.

and glucocorticoids e.g.

The side chain can removed completely and then changed to form

Look at iPad for whole diagram. Disorders come from excess/absence/abnormal function of enzymes within the hormone synthesis pathways

Hypothalamo Pituitary Adrenal Axis:

Hypothalamus releases

Then corticotrophs in APG release

then the

release cortisol. Hormones regulate hormones

POMC (Pro-opio-melanocortin): POMC is a large precursor protein that is cleaved to form a number of smaller peptides, including ACTH, MSH and endorphins

An increase in MSH leads to

therefore people who have pathologically high levels of ACTH may become tanned

Addisons disease:

Autoimmune disease where the immune system wipes out the adrenal

Autoimmune

– antibodies against the skin cause patches of depigmentation

Most common cause is

of the adrenal glands

No cortisol or

herefore increased POMC leading to increased ACTH and

leading to increased pigmentation of the skin

The lack of cortisol and aldosterone leads to

loss, reduces the blood pressure, therefore death from hypotension may occur

Urgent treatment of Addisonian crisis:

Rehydrate with normal

Give dextrose to prevent

which could be due to the glucocorticoid deficiency

Give cortisol replacement – hydrocortisone or other glucocorticoid

Cushing’s Syndrome:

Biological actions of excess cortisol:

Impaired

tolerance (diabetes)

weight gain (increase fat, lose protein), with fat redistribution – centripetal obesity

thin skin and easy

hirsutism-

and acne, striae (stretch marks)

proximal myopathy-

mental changes (depression)

Osteoporosis, hypertension, moon face- fat deposition in

buffalo hump

Causes:

Excess cortisol or other glucocorticoid:

Taking

by mouth.

pituitary dependent Cushing’s disease

Ectopic ACTH (lung cancer – glucocorticoid released from wrong location in body, i.e. the lungs)

Cushing’s syndrome – where the cause is

and clinical features observed

Cushing’s disease – where cause is determined to be

Aldosterone producing Adenoma:

In adrenal glands- Known as

syndrome

Hypertension, oedema and low potassium

In females – the gonads develop as the

In males – they develop as the

2 functions: Gametogenesis: production of gametes for reproduction - In males – spermatogenesis. In females – oogenesis

Steroidogenesis: production of steroid hormones

In males-

In females – oestrogens and progestogens

Gametogenesis:

Derived from

which multiply and increase in number before birth

In males,

levels remain relatively constant through life (6-7million)

In females, oogonia reach 5-6million by 24 weeks of gestations, but then

are produced. These then enter the first stage of meiosis where development is halted until puberty

Rapid

of oogonia occurs before birth, therefore at birth numbers have reduced to 2million

By puberty, < half remain, and by menopause number of oogonia is

Only 3-4 hundred ever reach ovulation

Spermatogenesis- Begins at

Some primary spermatocytes continually return to

stage- therefore a pool of spermatogonia remains available for subsequent cycles throughout life

Therefore retain some spermatogenic capability throughout life, producing 300-600 sperm/gm testis/second

Check notes for diagram

Oogenesis:

Initial number of oogonia in fetus is approx

- exist in primordial

Primary oocytes halted at

during first meiotic division

Then primordial follicles enter process of

- By birth the total number of oogonia is approximately 2 million, and by puberty < 0.5 million

Only at puberty under influence of

does the first meiotic division finish and the cycle continues

The last step of the cycle occurs at fertilisation

Germ cell>Oogonia>

>Secondary Oocyte+ first polar body>Ovum+

The Testes:

Spermatogenesis occurs in the

Spermatozoa are eventually released into the

of the tubules, where they migrate to the rete testis via collecting ducts

The spermatozoa are then drained from the rete testis via the

into the epidymis

They then mature in the epidymis, and are propelled to the

by the vas deferens which is surrounded by smooth muscle

Coiled seminiferous tubules:

Consists of a lumen surrounded by

connected by tight junctions in the periphery

Spermatogonia are engulfed into the sertoli cell, where they develop in the

into primary and secondary spermatocytes and are released into the lumen of the tubule as spermatozoa

outside the seminiferous tubule are

clusters, which are the site of testosterone production

Sertoli cells:

Form the seminiferous tubules and synthesise

and androgen receptors. Intimately associated with developing spermatocytes

Leydig cells:

Lie outside the seminiferous tubules. Synthesise

In response to LH are principal source of testicular androgens- mainly

The Ovaries

The ovarian stroma consists of: Primordial follicles undergoing atresia,

follicle just before ovulation and remnants of corpus lute

A graffian follicle consists of an ovum surrounded by

-A layer of

cells followed by a layer of thecal cells surround the fluid at the periphery of the follicle

Steroidogenesis:

From precursor

Products depend on enzymes – only the adrenals have the necessary enzymes for aldosterone and cortisol synthesis

The gonads synthesise: Progestogens (C21), Androgens (C19) and Oestrogens (C18)

The Menstrual Cycle:

Approx

Begins on 1st day menstruation

Ovulation occurs at day

Consists of: Ovarian Cycle – follicular phase, ovulation &

Endometrial Cycle – proliferative phase &

The endometrium consists of an epithelium and

layer- Changes are due to hormone changes in the ovarian cycle

The Follicular phase of the ovarian cycle – oestrogen (17β- OESTRADIOL) production – stimulates

phase of endometrial cycle

The luteal phase of the ovarian cycle – progesterone and 17β- Oestradiol production – stimulates

phase of endometrial cycle

The ovarian cycle:

Pre-antral follicle: Developed in the absence of

Ovum surrounded by layer of cells

Early antral follicle: Ovum surrounded by granulosa cells and

Follicle present – antral filled phase

Late antral follicle: Same as early antral follicle. Follicle increases in size, therefore more antral filled space surrounding ovum

Graffian follicle

Ovulation - Ovum released, cells form

Hormone Production during ovarian cycle:

Follicle influenced by FSH and LH, thecal cells produce

These stimulate the granulosa cells which contain

to produce 17β-Oestradiol

After ovulation, the corpus luteum converts androgens to 17β- Oestradiol

Endometrial cycle:

Menstruation: Days

Endometrium becomes necrotic and is shed

Proliferative phase: Days

Dominant hormone influence:

Endometrium: Thin endometrium forms and begins to thicken

Glands: Early phase has straight glands then late phase, the glands

, coil and have increased blood supply

Ovulation: Day 14

Secretory phase: Days

Dominant hormone influence: Progesterone (+oestrogen)

Endometrium becomes secretory, the glands secrete glycogen, mucopolysaccharides etc. Mucosa becomes engorged with

Summary:

LH and FHS peak at

Oestrogen peaks

ovulation

then troughs then is produced by the

so increases again, falls dramatically before menstruation.

Progesterone is limited to the

Oestrogen and progesterone exert negative feedback at the hypothalamus and anterior pituitary gland for

release. If fertilisation does not occur, oestrogen falls and menstruation occurs

Basal body temperature:

at ovulation. , indicator that ovulation is taking place - Attributed to the action of progesterone

Testosterone:

First androgen produced is

which is then converted to

Testosterone binds to the androgen receptor, and is the precursor to the more powerful androgen

- reduction involving 5-alpha reductase

-DHT has an increased affinity for the androgen receptor

Testosterone can also undergo

by aromatase to form oestrone and then 17-beta-oestradiol which is the main circulating oestrogen

Oestrogens also are important in the development of behaviour in males, and is therefore produced in the

cells of the testes as well as the ovaries in women

Testosterone and DHT are produced in: Prostate, Seminiferous tubules, Seminal vesicles, skin, brain and anterior pituitary gland

17-beta-oestradiol is produced in: Adrenals, Sertoli cells, liver, brain and skin

Transport of testosterone and DHT:

In blood – bound to plasma proteins as the androgens are

therefore need to be bound to prevent excess effects

Sex hormone binding globulin-

bound- Specific for androgens and oestrogens

Albumin – 38% bound

Free bioactive component – 2%

Principle actions:

In fetus - Development of male internal and external

- General growth (acting with other hormones, stimulates e.g. protein anabolism)

- Behavioural effects during development

In adults- Spermatogenesis

Growth and development of: male genitalia, Secondary accessory sex glands e.g.

Secondary sex characteristics e.g. receding hairline, facial hair, bulk, narrow hips

Protein

Pubertal growth spurt (along with growth hormone), Feedback regulation, Behavioural effects (CNS) e.g. aggression, competitiveness

Oestrogen:

Definition: any substance (natural or synthetic) which induces

in the endometrium. Examples o 17b-oestradiol (main one during menstrual cycle; most potent) o Oestrone (precursor) o Oestriol (main oestrogen produced in pregnancy)

Principal actions:

Final maturation of

during follicular phase of menstrual cycle. Induces LH surge resulting in

Stimulates growth and proliferation (mitosis) of the endometrium

Effects of vagina, cervix e.g. development of glands

Stimulates growth of

system of breasts

Decreases sebaceous gland secretion, which may be associated with

Increases salt (and water) reabsorption

Increases plasma

synthesis (hepatic)

Metabolic actions e.g. changing lipid profiles by stimulating HDL as opposed to LDL (possible protection for CVD)

Stimulates osteoblasts – lost after menopause, can have protective effect against

Influences release of other hormones, feedback regulation and behavioural influences

Progestogens:

Definition: any substance (natural or synthetic) which induces

changes in the endometrium. Examples: o Progesterone o 17-alpha-hydroxyprogesterone

Principal actions:

Stimulates secretory activity in the endometrium and

Stimulates growth of

system of breast

Decreases renal

reabsorption (competitive inhibition of the aldosterone)

Associated with increases in basal body temperature

Steroid Mechanism of Action:

Steroid hormones are

therefore pass through cell membranes. This means they must bind with

Hormone-receptor complex acts as a

molecule, binding with DNA to stimulate transcription etc

Have important genomic effects, but these are not seen instantly as takes time to make new proteins etc. Non-genomic effects are also possible.

Hypothalamo-Pituitary-Gonadal Feedback Loops:

The Hypothalamo-Pituitary-Testicular Axis-

Hypothalamus:

(GnRH) released in pulsatile patterns.

Anterior pituitary Gland:

Gonadotrophs release gonadotrophins:

Enter general circulation

Testis:

LH (in

cell) stimulates testosterone production, stimulating virilisation and

FSH (in

cells) stimulates

production. Also stimulates spermatogenesis.

Feedback:

Testosterone: Direct inhibition of

release from the anterior pituitary gland

Indirect inhibition of the pulse generator releasing GnRH from the hypothalamus, which in turn also reduced gonadotrophin (FSH & LH) release

Inhibin: Same effect as

Summary: – Endocrine control of testicular function

Androgen production - stimulated by GnRH/LH system - reduced by testosterone o direct negative feedback to reduce LH release from anterior pituitary gland o indirect negative feedback to slow hypothalamic GnRH pulse generator

Spermatogenesis - stimulated by GnRH/FSH system - also requires GnRH/LH/testosterone system for complete spermatogenesis - limited by inhibin negative feedback (direct and indirect)

The Hypothalamo-Pituitary-Ovarian Axis:

Same as testicular axis, except FSH and LH act on the

Must consider the effects of each hormone during the different phases of the menstrual cycle: o Early follicular o Early-mid follicular o Mid follicular o Late follicular o Luteal

Early follicular phase:

At the end of the previous menstrual cycle, there is a decreasing oestrogen and progesterone production, but the steroid hormones still result in an

of FSH and LH

o This is due to direct negative feedback on the anterior pituitary gland o Indirect negative feedback on the

Early-mid follicular phase:

The decrease in steroid hormones (oestrogen and progesterone) from the previous cycle reduces inhibition of

from the anterior pituitary, therefore LH and FSH are released

LH acts on

within the ovaries (binding to the LH receptor), inducing androgen synthesis o Androgens are then released into the general circulation, follicular fluid, or taken up by

cells within the ovary

FSH binds to FSH receptor on

cells, inducing the

of androgens to 17-beta- estradiol. This is known as a local positive feedback loop which enhances oestradiol production in developing follicles –

Mid-follicular phase:

The steps of the early-mid follicular phase continues, leading to an exponential increase of

which exerts a negative feedback effect resulting in decreased FSH and LH production

There is also a production of

from the follicle

Selective negative feedback loop by oestrogen and inhibin on the GnRH-FSH system results in

of all follicles that are still FSH dependent

Graffian follicle- largest follicle no longer requires

to develop and proliferate. It keeps growing and producing large amounts of 17b-oestradiol

Late follicular phase:

This rising concentration of 17b-oestradiol, in the absence of

or a minimum of 36h and at a certain level results in the positive feedback switch on the hypothalamo-adenohypophysial system. This triggers the LH

which stimulates the final development of ovum and ovulation.

There is also a surge in 17-alpha-hydroxy-progesterone just before this surge, which could be responsible for the final increase in oestrogen concentration

Luteal phase: After the gonadotrophin surges, there is an increase in the production of steroids

and

If fertilization does not occur, progesterone, oestradiol and inhibin exert a negative feedback on LH and FSH release, leading to

and menstruation. The steroid concentrations then start to decrease towards the end of the cycle

Clinical Correlates: Amenorrhoea-

Primary – never had periods Secondary- Did but have stopped

Oligomenorrhoea-

cycles

Infertility: Various causes: o Physical o Psychological o Emotional o Endocrine problems

Excess prolactin can cause it

Calcium: Most calcium is present in the body as

It is mainly found in

as complex hydrated calcium salt

In blood, some is present as ionized calcium (Ca2+), some bound to protein and the tiny bit left as soluble salts

Only the free (unbound) Ca2+ is

Roles:

Maintenance of neuromuscular excitability

Muscle contraction, strength in bones, intracellular second messenger, intracellular co-enzyme activity, ormone/neurotransmitter stimulus-secretion coupling and coagulation factor- factor

Handling by the body:

Intake via

Then absorbed via GI tract into the blood

From the blood, there are two target tissues:

Kidneys – small calcium ions enter the kidney

where final regulation of ion concentrations occur and excess is excreted via the urine

Bone (and all cells) – taken up from the blood, but calcium is also broken down and re-released into the bloodstream

There is also

loss of calcium via dead cells, hair, nails etc

In the blood:

The total concentration of calcium in the blood is approx

This is controlled very precisely, as many metabolic processes within the body are Calcium mediated

% of calcium remained unbound – this is the ionized component which is biologically active

% is bound to plasma proteins

5% remain as

Ion regulation:

Concentration is

by parathyroid hormone – a polypeptide hormone and 1, 25 (OH)2 vitamin D3 metabolite– a steroid hormone

Concentration is

by calcitonin – a polypeptide hormone with a physiological role that is not completely understood, but is relatively short lasting and increases in levels during pregnancy

PTH is released by

Calcitonin is released by

PTH:

Inititally synthesised as protein

84 amino acids long

Binds to transmembrane G-protein linked receptors

Activated

but also probably phospholipase C as a second messenger

Hormone Actions:

Kidneys: Increased Ca2+ reabsorption from tubular fluid in the proximal and distal tubules

Increased PO4^3-

Stimulates 1a hydroxyls activity, o This hydroxylases 25 OH Vit D3 to 1,25 (OH)2D3 o The 1,25 (OH)2D3 then acts on the small intestine

Small intestine: The 1,25 (OH)2D3 acts to:

Ca2+ absorption into the blood

Increase absorption of PO43-

these both lead to an influence in the blood calcium concentrations

Bones:

Stimulates osteoclasts-

Inhibits osteoblasts-

Effect on Blood:

Increased Ca2+ reabsorption and increased PO43- excretion from the kidneys leads to

Ca2+ concentration in blood

Increased Ca2+ and PO43- absorption from the small intestine leads to

Ca2+ concentration in blood

Increased Ca2+

due to increased osteoclast activity leads to increased Ca2+ conc in blood

Action in Bone:

PTH leads to the

of new bone formation

It binds with the PTH receptor on osteoblasts, which stimulate

OAFS stimulate osteoclasts to increase bone matrix breakdown and release Ca2+ and PO43- causing increased bone reabsorption

PTH Regulation:

Decreased plasma Ca2+ leads to

PTH production in parathyroid glands

This leads to increased Ca2+ which then carries out negative feedback on the parathyroid glands

Increased PTH causes synthesis of 1,25 (OH)2D3

This exerts a

influence increasing plasma Ca2+, but a

influence on the parathyroid glands to reduce PTH production, which then has a secondary effect reducing Ca2+

Catecholamines have a

effect on the parathyroid glands via beta receptors

Dihydroxy-cholecalciferol:

Synthesis- Diet and UV light

1, 25 (OH)2 D3 Actions:

On small intestine:

Ca2+ absorption

PO4^3- absorption

On bone:

Increased osteoblast activity o Therefore increased storage of Ca2+ in the bone

On the kidneys:

Increased Ca2+ and PO4^3-

in proximal tubule

Calcitonin:

Synthesised as

Calcitonin is 32 amino acid long polypeptide

Binds to transmembrane G-protein linked receptor which leads to the activation of adenyl cyclase or PLC as second messenger systems

Actions and regulation:

Stimulus:

concentration stimulates the parafollicular cells of the thyroid to produce calcitonin

Gastrin also stimulates this

Calcitonin action on bone – inhibition of

activity which decreases the plasma concentration

Calcitonin action on the kidneys – increased urinary excretion of

Clinical Correlates:

Hypoglycaemia: Endocrine causes-

Decreased Plasma [Ca2+]  Increased Plasma PO^43-  Reduced PTH

Pseudohypoparathyroidism-

Decreased Plasma [Ca2+]  Increased Plasma PO4^3-  Increased PTH

Vitamin D deficiency-

Plasma [Ca2+]

Decreased Plasma PO4^3-

PTH

Tetanty-

where smooth muscle goes into auto-contraction

Can be used to observe where

in Ca2+ have occurred

Trousseau's signs- tetany in the

can be induced by decreased Ca2+

Chvostek's signs- the facial nerve can be “tapped” to induce a twitch

Hypoparathyroidism- consequence of

idiopathic – cause unknown, hypomagnesaemia and suppression by raised plasma calcium concentration

Pseudohypoparathyroidism-

Due to target organ resistance to

Features include: particular physical appearance (short stature, round face)

IQ

subcutaneous calcification and various bone abnormalities (e.g. shortening of metacarpals)

associated endocrine disorders (e.g. hypothyroidism, hypogonadism).

Vitamin D deficiency-

Rickets in

Osteomalacia in

Clinical feature is the decreased calcification of bone matrix resulting in softening of bone- bowing of bones in children and fractures in adults

Hyperparathyroidism:

Endocrine causes: primary hyperparathyroidism, tertiary hyperparathyroidism and vitamin D toxicosis

Causes: Adenoma within the

leads to an increase in PTH, which increases the [Ca2+]. However there is no response to negative feedback seen.

This is

hyperthyroidism – results in clubbing of the fingers, and marked periosteal bone erosion in the terminal phalanges

Low plasma Ca2+ – e.g. due to renal failure; a decrease in [Ca2+] stimulates the parathyroids to produce PTH, which increases the [Ca2+] although there is no calcitonin release to counteract this, and there is

feedback. This is

hyperthyroidism.

Parathormone excess: On the kidneys- Ca reabsorption PO4 excretion Polyuria Renal stones Nephrocalcinosis 1,25 (OH)2 D2 synthesis

On the GI tract: Gastric acid and duodenal ulcers

On bone:  Bone lesions  Bone rarefaction  Fractures

In the

It's shaped like a

Embedded within it are 4

glands: right and left superior and inferior

They consist of different cells and are important in metabolism of

Its origin is at the

Development starts in utero after

where a midline outpouching forms of the floor of the pharynx

The outpouching then forms a duct known as the

duct which migrates down the neck and divides into two lobes

Reaches final position by week 7, where the duct disappears leaving dimple in tongue known as the

Thyroid gland then develops

Structure: Adult weight:

Each lobe = 4x2.5.2.5 cm

Consists of 4 lobes: right, left,

and

The biggest lobe is the

The nerve which runs close to the thyroid is the left

nerve which is responsible for supply of

Problems with development:

– complete absence

Incomplete descent – from base of tongue to

Thyroglossal cyst – segment of duct persists and presents as lump years later

Thyroxine is essential for development of the

It controls cellular activity and neonates with deficiency in utero have irreversible brain damage-

Cretin – an individual with irreversible brain damage caused by lack of thyroxine, they're mentally sub-normal and have a

Cretinism prevention – babies at 5-10 days have heel prick

o Thyroid function – measures

if the levels are

thyroxine is given immediately

o Guthrie test – tests for

The thyroid follicular cell is the site of

Also known as Thyrocyte. Controls

Thyroxine binding globulin binds

of thyroxine in the circulation (NOT THYROGLOBULIN – this is present in the thyroid gland)

The thyroid gland is normally responsible for synthesis, storage and secretion of thyroid hormones

Thyroid disease affects 5% of the population

The ratio of females affected to males affected is

Overactive: underactive = 1:1

Primary hypothyroidism is also known as

Caused by

damage to the thyroid, or surgical removal

Underactive thyroid gland

Primary thyroid failure: decline in

by thyroid gland. Anterior pituitary gland detects this fall and secretes

- thyroid stimulating hormone and normal HPT axis: hypothalamus secretes TRH

which stimulates anterior pituitary to secrete TSH, which stimulates thyroxine release from the thyroid.

Thyroxine release then exerts a

effect on both the hypothalamus and the antierior pituitary

Features: Decrease in

Their voice will

Depression and tiredness, intolerance to

Weight gain with reduced appetite, constipation and heart rate <60bpm-

Eventual myxoedema coma

Treatment is essential, if not treated then

increases causing death from MI/stroke

Treatment includes thyroxine replacement

A primary hyperthyroidism is known as

which means an overactive thyroid gland which makes too much thyroxine

TSH levels go to

Increases BMR and body temperature which is causes

heart rate is >100bpm so is known as

Increase metabolic rate of all cells

Features: Mood swings, restlessness, difficulties with

Feeling hot in all weather, diarrhoea, increased appetite but

Tremor of hands, palpitations, sore eyes and an enlarged thyroid which is known as

Causes: Graves' disease

Whole gland is smoothly enlarged and the whole gland is

Systemic disease of the whole gland

Autoimmune – antibodies bind to and stimulate the

in the thyroid, stimulating thyroxine release

Leads to goitre and hyperthyroidism

Other antibodies bind to muscles behind the eye, causing muscle hypertrophy and a swollen eye which is known as

Other antibodies stimulate the growth of the

and cause pretibial

Hypothyroidism: Secondary hypothyroidism is caused by

Causes of hypothyroidism are surgery, autoimmune disease, resistance to TSH and deficiency of

Hyperthyroidism: Causes are autoimmune disease such as

or

-a TRH producing tumour in the hypothalamus; a TSH producing tumour in the hypophysis

Mechanism of the effects of hyperthyroidism: Thyroid hormones cause sensitisation to

This leads to

Treatment of hyperthyroidism: PTU- stops thyroxine production, radio-labelled iodine which destroys part of the gland.

The adrenal glands lie on top of the

and consist of: the adrenal

– core of the gland

and the adrenal

– outer layers surrounding the core.

The adrenal cortex consists of 3 layers, known as cortical zones. The outer layer is the

The middle layer is the

and the inner layer is the

The adrenal gland is then finally surrounded by a

Functionally, the medulla and cortex act as separate endocrine glands, as they are involved with the synthesis and release of different hormones: The medulla releases

The cortex releases

Cortical zones: Arterial blood supply flows

the capsule surrounding the gland

There are then two ways that blood is transported through the different cortical zones to the medulla:

1. Blood perfuse through cells until it reaches the

in the centre of the medulla

2. Clearly defined

flow from the outer capsule to the medulla

The three cortical zones are layers of different cells that have grouped together: The section with the most recognisable structure is the

It has lines of cells which run towards the zona reticularis

The other two aren't easily distinguishable

The medulla is made up of

cells. These cells synthesise and release

They are polypeptide hormones synthesised from a

precursor.

Adrenal hormones: Catecholamines- Released by the medulla

80%

and 20% noradrenaline. Dopamine is also an end point of synthesis of catecholamines.

Corticosteroids: Released by the

Divided according to principal functions: Mineralocorticoids- aldosterone which is the principle human hormone

Glucocorticoids- principally

and sex steroids - androgens

Steroid hormones are all synthesised from the same precursor which is

The adrenals are responsible for synthesis of mineralocorticoids and glucocorticoids, the

are responsible for synthesis of androgens.

Corticoid transport- corticoids are

therefore can easily cross cell membranes where they bind with intracellular or nuclear membrane receptors

Therefore these hormones can't be

as this will result in excessive binding with receptors and hence over stimulation

Because of this, the hormones can be produced on demand, or bound to plasma proteins in the blood to prevent their action. They act as a store.

Cortisol: 75% bound to CBG-

15% are bound to the non-specific protein

10% of the hormone is unbound and

Aldosterone: 60% bound to CBG and 40%

In regards to the synthesis pathways, 21-hydroxylase and

are important enzymes. Look at notes for this! p36

Circulating concentration:

Cortisol- controlled by the

and is released in

which vary depending on time of day. This is known as

Aldosterones – released in pulses, and depend on body positioning

cortisol is measured in nanomoles/l, whereas aldosterone is measured in

Nanomoles are 1000x greater than picomoles

Stimulates

reabsorption in distal convoluted tubule and cortical collecting duct

It also stimulates

and H+ secretion also in distal convoluted tubule and cortical collecting duct. This is the only physiological way of removing potassium from the body

Mechanism of action: Aldosterone diffuses into the distal convoluted tubule from the

It then binds with an