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43 Cards in this Set

  • Front
  • Back
What is endocrinology?
Endocrinology is the study of the internal secretions of the body (the function of the "so-called" ductless glands).
What kind of questions does endocrinology involve?
How do we, as organisms, sense our external and internal environments and adjust to how they are changing?

How do we organise our reproduction to ensure the continuation of the species?
What are the two major systems involved in communication?
Nervous system
(specific neural connections, neurotransmitter)

Endocrine system
(release of small amounts of biologically active substances into large volumes; specialised signalling molecules to achieve specificity of action)
What are some functions of communication?
Communication essential for maintenance of bodily functions
"Sensing" information and "respoding"
May also be voluntary
Critical to the concepts of homeostasis and achieving critical goals and needs
What are the two modes of communication?
Electrical

Chemical messngers
What is synaptic tranmission?
Production, release, reception and metabolism of chemical messengers
Rapid effects
What are the organs in the endocrine system? (11)
Hypothalamus
Pituitay
Pineal body
Thyroid and Parathyroid
Heart
Thymus
Adrenal gland
Kidney
Pancreas
Ovary
Testis
The traditional view of the endocrine system is just organs. What is the more complex view?
Every cell in the body is exposed to an "endocrine milieu", and is capable of making or modifying hormones.

The largest endocrine tissue in the body is therefore the skin followed by fat.

The stomach is an important endocrine organ.
What is a hormone?
A hormone is a chemical that is released from one site and acts in a different site to bring about a biological effect.
What are the three different terms describing how hormones are released and act?
Endocrine - released into blood

Paracrine - released and acts adjacent

Autocrine - released and acts on same cell
Is a neurotransmitter a hormone?
Yes (paracrine or autocrine)
What are the differences between a neurotransmitter (paracrine or autrocrine) and a hormone relased into the blood stream to act at a distant site (endocrine)?
Concentration, protection against degradation, physical characteristics of the receptors.
What are hormones made of?
Peptide/protein derivatives: made in cells following transcriptional/translational events

Synthesised from precursors:
Cholesterol (steroids)
Arachidonic Acid (prostaglandins)[Fatty acid derivatives/eicosanoids]
Amino acids (catecholamines, thyroid hormone)
What are the two different kinds of hormone receptors?Describe them.
Cell surface receptors - for peptide/protein hormones. Generation of second messengers which alter the activity of other molecules - usually enzymes - within the cell. broad range of signalling pathways (cAMP, PKC, Ca2+, MAPK etc). Rapid and sustained effects.

Intracellular receptors - for steroid hormones. Alter transcriptional activity of responsive genes. Transcription activation factors regulate gene expression. Sustained effects
What factors affect the concentration of a hormone?
Secretion rate

Degradation rate
- specific enzymatic degradation
- generalised degradation and elimination (liver and kidneys)
- protein binding (specific and generalised e.g. albumin)
What does the hypothalamus control?
Autonomic nervous system
Temperature regulation
Water balance
Food intake and energy balance
Emotions and behaviour
Endocrine secretions from the pituitary gland
Describe neurosecretion.
- 1930s - recognised that neurones of the hypothalamus project to teh posterior pituitary (neurohypophysis)
- these neurones originated in either the Supraoptic Nucleus (SON) or Paraventricular Nucleus (PVN). Have large cell bodies (magnocellular)
- Histological examination of these neurones showed many dense granules in their axons
- it was hypothesised that these neurones secrete hormones from the posterior pituitary
- It is now well recognised that these neurones secrete arginine vasopressin (AVP or ADH) or oxytocin.
- About the same time a number of workers were making electrical manipulations of the hypothalamus and affecting secretions of the anterior pituitary gland
Describe the hypothalamus and pituitary blood supply.
--> The supierior hypophysial artery supplies a structure at the base of the hypothalamus known as the median eminence.
--> within the median eminence a capillary plexus forms
--> the capillaries then coalesce into veins that run along the anterior face of the pituitary before they dive into the anterior pituitary where another capillary plexus forms
--> the veins that run along the anterior pituitary are therefore portal
--> like the hepatic portal system they are capable of transporting products from one site to another

- it was also noticed tha tht eneurones of the hypothalamus that projected to the median shared some of the same features of the AVP- and OT-neurosecretory neurones
What is the Harris hypothesis?
1. Blood flowed from the hypothalamus (median eminence) to the anterior pituitary
2. Hypothalamic factors which regulate anterior pituitary hormone secretion are released into this portal system at the median eminence, and hence make their way to the anterior pituitary
3. The secretion of anterior pituitary hormones involves a balance between positive (stimulatory) and negative (inhibitory) hypothalamic influences
4. For each anterior pituitary hormone there would exist a hypothalamic stimulator and inhibitor
Describe the embryology of the pituitary gland.
- the anterior pituitary originates from Rathke's pouch (an ectodermal evagination of the oropharynx)
- the posterior pituitary is of neural origin and arises from the ventral hypothalamus and 3rd ventricle
- during fetal life there exists and intermediate lobe of the pituitary
- this becomes less distinct during extrauterine life
Describe the histology of the pituitary gland.
- The anterior pituitary is largely comprised of the cells that secrete the anterior pituitary hormones
- The neural lobe consists of nerve terminals of the neurones from the SON and PVN and supporting cells known as pituicytes
List the cells of the anterior pituitary gland and what they secrete.
SOMATOTROPHS - Secrete Growth Hormone (GH)
~50% of anterior pituitary cells

LACTOTROPHS - Secrete Prolactin (PRL)
~10-25% of anterior pituitary cells (sex)

THYROTROPHS - Secrete Thyroid Stimulating Hormone (TSH)
~10% of the anterior pituitary cells

GONADOTROPHS - Secrete Follicle Stimulating Hormone (FSH) and Luteinising Hormone (LH)
~10-15% of the anterior pituitary cells

CORTICOTROPHS - Secrete Adrenocorticotrophic Hormone (ACTH)

FOLLICULO-STELLATE (FS)
- Function still under debate
- Secrete interleukins and other products
- May play a role in paracrine interactions between pituitary cells
The GROWTH HORMONE FAMILY
(and some synonyms)
Growth Hormone
- GH
- Somatotrophin

Prolactin
- PRL
- Mammotrophin

Placental lactogen
-PL
- Chorionic somatomammotrophin

All these hormones are structurally similar, and the cells of the anterior pituitary which make GH and PRL are evolutionally related.
Describe GH production.
- GH is made by somatotrophs
- These cells comprise about 50% of the cells of the anterior pituitary
- The number of somatotrophs is regulated by a variety of physiological mechanisms (e.g. stage of life puberty, oestrogen concentrations)
- important concept of mammosomatotroph precursor cell
Describe GH biochemistry.
- GH is a single polypeptide hormone
- 191 alpha alpha - 21 500 MW , 2 disulphide bridges
- significantly similar to placental lactogen (chorionic somatomammotrophin)
Describe PRL production
- PRL is made by lactotrophs
- these cells make up about 25% of the cells of the anterior pituitary
- the number of Lactotrophs is somewhat regulated by oestrogen
Describe PRL biochemistry.
- PRL is a single polypeptide hormone
- 198 alpha alpha - 22 000 MW, 3 disulphide bridges
- significantly dissimilar to placental lactogen (chorionic sommatomammotrophin)
The GONADOTROPHINS
Leuteinising hormone and follicle stimulating hormone

- glycoproteins which are composed of two subunits - alpha and beta
- the alpha subunits are identical between the 2 gonadotrophins
- specific differences exist in the beta subunits
Describe Gonadotrophin biochemistry.
alpha subunit - 92 alpha alpha

beta subunit - 115 alpha alpha

overall molecular weight ~ 30 000

- a number of glycosylataion sites exist on both chains
- the glycosylations have an important effect on half-life and biopotency
- LH and FSH share the glycoprotein structure with thyroid stimulating hormone (TSH) and human chorionic gonadotrophin (hCG)
- the beta chain of hCG has significant similarity to the beta chain of LH

Other names
Human menopausal gonadotrophins (hMG)
Interstitial cell-stimulating hormone (ICSH)
Describe TSH production and biochemistry.
- thyrotrophs make up about 10-15% of the cells of the anterior pituitary

- TSH is a glycoprotein molecule (like LH and FSH)
- it therefore has a common alpha chain, and a unique beta chain
- overall molecular weight 28 000
- a number of glycosylation sites
Describe ACTH production.
- Corticotrophs make up about 10% of the cells of teh anterior pituitary
- In species where there is a prominent intermediate lobe (IL), all of the secretory cells of teh IL make ACTH-like products, but the cells are known as melanotrophs
- In melanotrophs about 30% of the total protein comes from the precursor to ACTH
Describe ACTH biochemistry.
- ACTH is a 39 alpha alpha peptide
- the 1st 24 alpha alpha confer biological activity and are the same in all species except the guinea pig

- ACTH is derived from a large precursor molecule known as: PRO-OPIOMELANOCORTIN (POMC)

- This precursor gives rise to a large number of diverse peptides including:
> the endorphins melanocyte stimulating hormones (MSH)
> and several others with putative biological functions
What is feedback?
- Feedback is a fundamental engineering concept in the control of many biological systems
- What it implies is that a trophic organ sends a message to stimulate an end-organ and the signal from the end-organ is sensed and the resultant output of the trophic organ modulated
- Most often this is negative feedback (keeps end-organ output under tight control)
- can be positive feedback - must end in cataclysmic event
Synonyms of Vasopressin
Arginine Vasopressin(Lysine Vasopressin)
AVP (LVP)
Anti-diuretic hormone
ADH
Desmopressin
Synonyms of Ocytocin
Syntocinon
Vasotocin
Describe the neuroanatomy of Vasopressin and Oxytocin.
- These two peptides are made in the magnocellular neurones in the Supra-optic nuclei (SON) and Paraventricular nuclei (PVN)
- the neurones from this region are non-myelinated, and course down through the internal zone of the median eminence to the posterior pituitary (neurohypophysis)
- The neurones in this region abut fenestrated capillaries formed from the inferior hypophyseal artery

Other important terms
Pituicytes - glial cells of the neurohypophysis
Herring bodies - varicositites of the neurones
Describe the peptide structure of vasopressin and oxytocin.
Both are nine alpha alpha peptides with a disulphide ring structure, and an amidated C terminus

They differ in the identity of the 3rd alpha alpha
- Isoleucine in Vasopressin
- Phenylalanine in Oxytocin

And the 8th alpha alpha
- Arginine or Lysine in Vasopressin
- Leucine in Oxytocin
Describe the biosynthesis of vasopressin and oxytocin.
These peptides are synthesised from a large precursor.

The products of these include compounds known as neurophysins, which are co-stored and secreted with vasopressin or oxytocin

Neurophysin I - product of the precursor of oxytocin

Neurophysin II - product of the precursor of Vasopressin

Function of the neurophysins is unknown

Brattleboro rat
Describe the regulation of Vasopressin secretion.
There are two important stimuli:
1. Osmolality
2. Blood Volume

Regulation by osmolality is very tight (changes of 1-5% cause changes in vasopressin levels).

Changes in Blood volume in the order of 15-30% are necessary for changes in vasopressin levels.

Interaction between the two factors.

The changes in osmolality are detected directly at the neurones in the hypothalamus, or via brainstem.

Changes in blood volume involve baroreceptors and are relayed via the brainstem.

Some drugs can modulate Vasopresin release (alcohol).
Describe the actions of vasopressin.
Acts to restore blood volume and pressure.

The actions are mediated via G protein-linked receptors

V1a receptors - linked to PLC, mediate actions of vasopressin at arterial smooth muscle (vasoconstriction) and on hepatocytes (glycogenolysis)

V1a receptors - linked to PLC actions at the corticotroph to increase ACTH secretion

V2 receptors - linked to adenlyate cyclase and the cAMP, mediate actions of Vasopressin at the kidney (increase H2O reabsorption)
What are the disorders of Vasopressin?
Diabetes insipidus (decreased vasopressin action)
1. Neurogenic
2. Nephrogenic

Syndrome of inappropriate ADH (SIADH)

Occurs in situations of chronic illness or postoperative states

Hypotonicity, hyponatraemia
Describe the regulation of Oxytocin secretion
Stimuli to secretion
1. Parturition
2. Nipple stimulation
3. Intercourse
4. Hypertonicity
Describe the actions of Oxytocin.
These are mediated via receptors that are linked to PLC.

Relatively high specificity between Vasopressin and oxytocin.

Actions:
1. Smooth muscle contraction during the sucking (let down reflex)
2. Smooth muscle contraction during parturition