Endocrinology

What is the endocrine system?

Collection of glands that produce hormones that regulate physiological functions

What physiological functions do hormones regulate

Metabolism, growth and development, tissue function, sexual function, reproduction, sleep, mood

Signals of the nervous system VS endocrine system

-signals of neurons in nervous system are precisely targeted
-Endocrine they are broadly distributed through the body

For a hormone to elicit a specific response from a cell, the cell must ________-

Possess specific receptor proteins for that hormone

Hormone signals

Slow, longer timescales - circulate in blood to target tissue

Target Cells

cells that have receptors for a particular hormone

What happens when there is no receptor or it is the wrong receptor for a hormone?

No effect on the target cell

Do hormones circulate indefinitely

No, they synthesize

What are the three classes of hormones?

Amine hormones, steroid hormones, peptide hormones

Steroid hormones are synthesized from

cholesterol (made by the liver)

How long is a steroid hormones half life

hours

In vertebraes what is steroid hormone secreted from

gonads, adrenal cortex and placentas of pregnant animals

Are steroid hormones lipid soluble

yes

How do steroid hormones reach the receptor

pass through cell membrane

What are peptide/protein hormones made of

Chains of amino acids varying in size

Are protein hormones soluble in aqueous solutions?

Yes

What are protein hormones secreted by

exocytosis

Steps of peptide hormone synthesis

1. Prepropeptide is synthesized and released into the Rough ER
2. Proteolytic enzymes in RER cleave off some amino acids to yield pro peptides
3. In the smooth ER, pro peptides are packaged into transport vesicles
4. vesicles are transported to the golgi complexes
5. Golgi complexes package the propertied into secretory vesicles (more AAs cleaved in GA or secretory vesicles to yield final peptide)
6. Peptides are released by exocytosis

Amine Hormones half life length

Could be seconds, minutes or days

What are amine hormones derived from

Tyrosine and tryptophan

What can water soluble hormones do? (protein hormones)

- secreted by exocytosis
-Travel freely in the bloodstream
-Bind to cell-surface receptors
RECEPTORS ON OUTSIDE OF CELL

What can lipid soluble hormones do

-Diffuse across cell membranes
-Travel in bloodstream bound to transport proteins
-Diffuse through the membrane of target cells

What do steroid hormones need in plasma

A carrier! They are lipid soluble

What are transporters of steroid hormones

Transcortin, albumin, sex hormone binding globulin, other plasma proteins

What is most of cortisol bound to

Corticosteroid binding globulin (transcortin)

What is a small percentage of cortisol bound to

Albumin

What percentage of cortisol is free

8 percent

What is most of aldosterone bound to

Albumin

What is a small percentage of aldosterone bound to

transcortin and other plasma proteins

How are hormones protected from metabolism

If they are bound to transport proteins

What do transport proteins assist in

Maintaining concentration of hormone in circulation

Can Steroid hormones enter the cell and interact directly with cell nucleus through the formation of a complex with its systolic receptor?

Yes

Can protein hormones enter the cell and interact directly with cell nucleus through the formation of a complex with its systolic receptor?

No! They need a second messenger because they cannot enter the cell (water soluble)

Steps of steroid hormone entering the cells

1. Hormone interacts with the receptor
2. Hormone moves into the nucleus (translocates)
3. The hormone interacts with its responding elements
4. This makes mRNA and protein
5. Biological effect

Steps of protein hormones entering cell

1. Hormone interacts with the receptor
2. Adenylate cyclase is activated/started up
3. This produces cAMP
4. Protein kinase phosphorylation occurs
5. biological effect occurs

What does the inactivation of steroids involve

Reducing and conjugating glucuronides or sulfate to increase their water solubility
-Most catabolized by the liver and kidneys

Where are most of the conjugated steroids excreted? Where does a small percentage go?

Most are excreted in the urine and some leave in the feces/exit through the skin

Is the metabolism of hormones a constant rate

Yes - normally

Negative feedback

A type of regulation that responds to a change in conditions by initiating responses that will counteract the change. Maintains a steady state.

Example of negative feedback

body temperature regulation or riding a bike (increasing hormone concentration is like faster pedaling, and negative feedback is applying the brakes)

Positive feedback loop

Causes a system to change further in the same direction.

example of positive feedback

childbirth

Where does the hypothalamus control secretion of tropic hormones from?

Anterior pituitary

If blood concentrations increase beyond that physiological set point what happens?

Releasing hormone output is decreased

Decreased = tropic hormone is released
Decreased = target organ hormone is released

What gland is the control center and where is it in the brain and what does it do

Hypothalamus, attached to roof of third ventricle near the thalamus
-Continuously receives info on the status of body systems through nerve impulses
-Monitors the composition and temp of blood
-Messages are interpreted here and evaluated - outgoing messages are dispatched via nerves/hormones
-Plays role in feedback system that governs secretion of endocrine system

What is the pituitary gland also known as

hypophysis

What is the pituitary gland composed of

Anterior lobe (adenohypophysis)
-Pars tuberalis
-Pars intermedia
-Pars distalis

Posterior lobe (neurohypophysis)
-Pars nervosa

Anterior lobe of the pituitary gland activity is controlled by and what does it stimulate

Hypothalamic releasing hormone (released into blood portal system) - stimulates release of various anterior pituitary hormones

Posterior lobe is composed of _______ whose neural origin is within the _______

axons, hypothalamus

What is an extension of the hypothalamus into the pituitary (ie cell bodies are in hypothalamus)

Posterior lobe of the pituitary gland

What forms the stalk of the posterior lobe

axons

What are the hormones from the posterior pituitary

ADH (antidiuretic hormone) and oxytocin

What are the hormones from the anterior pituitary gland

FSH (follicle stimulating hormone), LH (luteinizing hormone), PRL (prolactin), ACTH (adrenocorticotropin hormone), TSH (thyroid stimulating hormone

Grow hormone: secretory cell type, target and effector

Somatotrope, liver and adipose tissue, and stimulation of growth and metabolism of CHO and lipid

Prolactin:secretory cell type, target and effector

Lactotrope, mammary glands, production of milk

TSH :secretory cell type, target and effector

Thyrotrope, thyroid gland, secretion of thyroid hormones

FSH: secretory cell type, target and effector

Gonandotrope, ovaries and testes, production of sex hormones

ACTH: secretory cell type, target and effector

Corticotrope, adrenal gland (cortex) and secretion of glucocorticoids

What is the most abundant cation in the body

calcium

What bodily functions is calcium important for?

Muscle contraction, nerve cell activity, activation of enzymes, release of hormones through exocytosis, blood coagulation, cell membrane stability
-Important in maintaining structural integrity of teeth and bones

Why is phosphate important in the body

For the structure of bone and teeth; organic phosphate part of cell membranes and intracellular components, H+ buffering in blood

Where are the pools of calcium in the body

1. Bone - 99 percent of all calcium as hydroxyapatite crystals which also have phosphate
2. Intracellular calcium = calcium bound to proteins or contained in mitochondria
3. Extracellular fluid - comprises interstitial calcium, blood calcium and .5 % of bone calcium pool (amorphous crystals in solution) soluble bone calcium pools allow access to large reserve of calcium in bone

What does the regulation of calcium levels involve

Control of the movement of calcium between the ECF and 3 body organs (GI, bone and kidneys)

Calcium in the GI

Absorbed across the mucosa both passive diffusion and active transport pump, pump becomes more active when dietary calcium is low

Calcium in the kidneys

Route of calcium excretion, most of calcium is reabsorbed and only 2% is lost, distal tubules under hormonal control sites of calcium regulation in kidney

What is the most important organ in calcium regulation

bone

Amorphous crystals and soluble calcium lies between

osteoblasts and osteoclasts

What mobilizes calcium

Osteoclasts - ready exchange of calcium ions with the blood

Which hormones are involved in the regulation of calcium

Parathyroid hormone and calcitonin

What is the main organ involved in calcium phosphate homeostasis

Parathyroid gland

What secretes parathyroid hormone

parathyroid gland

What is the effect of PTH

To increase calcium and phosphate concentrations in ECF

PTH has direct effects on _____ and _____ and has indirect effects on ______

direct : bone, kidneys
indirect : GI metabolism of calcium

Release of calcium acts on the distal convoluted tubule of the kidney to increase calcium absorption and increase GI absorption via vitamin D activation (kidney)

Calcitonin is released by

thyroid gland, parafollicular or C Cells

What is the counterbalance for PTH

Calcitonin, it decreases the movement of calcium from bone and decreases ECF calcium
-Decreases GI activity
-Increases renal calcium excretion

Increased calcium does what to calcitonin

Increases calcitonin release

What has to happen for vitamin D to become active

HAs to be transformed by the liver and kidney

Causes of hypercalcemia

-Malignancy
-hyperparathyroidism
-Fungal disease
-Osteoporosis
-Chronic renal disease
-Hypervitaminosis D

What can happen with hypercalcaemia

Can progress rapidly to acute renal failure because of mineralization of renal tissue

Causes of hypocalcemia

-Post-thyroidectomy
-Chronic and acute renal failure
-acute pancreatitis
-Ethylene glycol intoxication

What can hypocalcemia progress to

Parenthesis, hyperventilation, tetany and seizures

Milk fever

low blood calcium causing muscle weakness at/or near calving

What are characteristics of complex regulatory systems?

Redundancy and pleiotropy - especially when regulated by cytokines

Is the calcium in bone readily mobilized by osteoclasts? What kind of storage is it?

Yes and is long term storage

Is intracellular calcium mobilizable?

No - has to be regulated

Is extracellular fluid calcium mobilizable? Is there a large or small pool

Highly mobilizable - smallest pool

Is the GI tract calcium mobilizable? Is there a large or small pool of it?

Highly mobilizable, potentially large pool

What kind of calcium is the most important and why

Unbound, ionized calcium plasma, it is seen by the calcium sensing receptor (CaSR) in the thyroid

Hypocalcemia is also called

milk fever

Most labs measure what for calcium - and what can get confused?

Most labs measure total calcium, so hypoproteinaemia can be confused with hypocalcemia

What three hormones control calcium homeostasis

PTH, CT; 1,25-(OH)2D3) and receptor CaSR

RANKL

a chemical that stimulates production of more osteoclasts

Osteoprotegerin

protects you from RANK-RANKL

decreasees RANK-RANKL binding, so decreases OSTEOCLASTS

What can you take from bovine blood to stimulate them to differentiate into multinuclear TRAP+ osteoclasts and what is this going to be used for

CD14 +/CD16 monocytes
-Going to be used to test the hypothesis that a form of autoimmunity is a contributing factor to parturient hypocalcemia in dairy cattle

What causes an acute onset of clinical signs for hypocalcemia syndromes

Sudden fall in Ca++ plasma

What is a feature of hypocalcemia in most species and what is the feature in bitches, cattle and sheep

Cardiovascular collapse and eclampsia in bitches, milk fever/parturient paresis in cattle, hypocalcemia in sheep, and transit tetany in sheep and cattle

What is a very common disease of dairy cattle

Milk fever or parturient paresis

What happens to most calving cows (calcium related)

Fall in calcium plasma for a day or so after calving but most are able to mobilize enough Ca from GIT and bone and they show no signs

Risk factors for milk fever

Diet: reduced prepartum feed intake, low Mg intake
Genetic : heritability moderate; common in jerseys
Production: affects high production cows
Season: late summer and autumn

Pathogenesis of milk fever

1. Decrease in smooth muscle contractility (vascular and gastrointestinal)
2. Decrease in cardiac muscle contractility
3. Decrease in skeletal muscle contractility
4. Neurotransmitter function
5. Apocrine gland function