What is the endocrine system
A collection of glands that produce hormones that regulate metabolism, growth and development
What does the hypothalamus and pituitary (HP axis) do?
Regulates the function of the thyroid, adrenal and reproductive glands
Controls somatic growth, lactation, milk secretion and water metabolism
The anatomy of the pituitary?
Lies in a pocket of bone at the base of the brain (just below the hypothalamus)
Contains two lobes: posterior and anterior
The anterior pituitary characteristics?
It has a unique blood supply
Release factors into the anterior
2 neurosecetory cells that secrete releasing hormones.
The posterior characteristics?
Portal system
Direct hormonal secretion into posterior.
3 neurosecetory cell bodies.
What does the posterior do?
Role in body fluid homeostasis and reporudctive function.
Magnocellular neurons in paraventricular and supraoptic neurones secrete oxytocin and vasopressin into the posterior lobe.
Vasopressin for water reabsorption
Oxytocin: lactation and labour
ADH (vasopression) and oxtoycin is synthesised where?
In the cell bodies of the hypothalamic neurones
ADH: by the supoaptic nucleus
Oxytocin: by paraventricular nucleus
Synthesis process of ADH and oxytocin
Both are synthesised as pre-prohormones
Processed into 9 amino acid peptides.
Released from axonal termini in response to AP.
Axonal swelling due to storage of secretory granules are termed Herring bodies.
Difference between ADH and oxytocin in structure?
Both are nonapeptides (9AA)
Differ in 2 amino acids.
Cys- Tyr- Phe/Gln-Gln-Asn-Cys-Pro-Arg/Leu-Gly-NH2
Use of ADH
Water reabsorption in the kidney.
Contraction of smooth muscle
Maintance normal osmolarity of body fluids.
Use of oxytocin
Contraction of uterine smooth muscle
Childbirth
Primary target of ADH
Cells lining the distal renal tubule.
Principle cells of the collecting ducts of the kidneys.
How does ADH bring about its action?
Binds to vasopressin 2 receptors on basal side of renal cells.
Vasopressin-2 receptors is a GPCR linked to the Gs-cAMP-PKA pathway.
V2R signalling boosts insertion of aquaporin2 into apical membrane (causing water to be taken in).
Causing more water to be reabsorbed.
In the presence of ADH what happens into urine flow and osmolarity (conc)?
Urine flow decreases
Urine osmolarity increases
In the absence of ADH what happens to urine flow and osmolarity?
Urine flow increases
Urine osmolarity decreases
ADH is released in response to?
Increase in extracellular fluid osmolarity
Decrease blood volume and pressure
Increased osmolarity stimulates the magnocellular cells to release ADH
Cardiovascular volume receptors stimulate these cells when there is a drop in blood volume.
Oxytocin mechanism?
Stimualtes contraction
Stretching of the cervix stimulates oxytocin release.
Postive feedback causing a stimulation of stretching causing more oxytocin release.
At birth, stretching is weakened and no postive feedback
Anterior pituitary?
Connected to hypothalamus by hypophyseal-portal circulation.
Made up of hormone producing glandular cells.
Produces 6 peptide hormones
Name the 6 peptide hormones the anterior pituitary produces?
Prolactin
Growth hormone
Thyroid stimulating hormone
Adenocarticotorphic hormone
Follicle-stimulating hormone
Lutenising hormone
The connection between hypothalamus and anterior pituitary?
Parvicellular neurosectory cells secrete releasing factors into capillaries of the pituitary portal system.
Factors are transported to the anterior pituitary to regulate secretion of pituitary hormones.
Anterior pituitary control?
From hypothalamus to pituitary is controled by hypothalamic releasing hormone.
From pituitary to end organ is controlled by putuitary hormone.
The end hormone is controlled by the end organ hormone.
Name the 7 hypothalamic releasing hormones and what do each of them do?
CRH: stimualtes ACTH secretion.
TRH: stimulates TSH secretion.
GHRH: stimulates GH secretion.
Somatostatin: inhibits GH secretion.
GnRH: stimulates LH and FSH secretion.
PRH: Stimulates PRL secretion.
PIH: inhibits PRL secretion.
Name the 6 hormones produced by the anterior pituitary?
Thyrotrophin: thyroid gland regulation.
ACTH: adrenal cortex regulation.
FSH: Ovulation in females and spermatogensis in males.
LH: Regulates testersterone in males and ovulation in females.
Growth hormone: Regulation of metabolic processes for growth.
Prolactin: mammary development & lactation.
Feedback regulation of the H-P axis?
Ability of hypothalamic releasing hormones to provide negative feedback.
Thyroid stimulating hormone (TSH)
Glycoprotein hormone.
Heterodimer composed of an alpha and beta subunits.
Binds to TSH receptors on thyroid epithelial cells.
Control every aspect of the thyroid function.
Stimulated by TRH
Thyrotropin-releasing hormone (TRH)
Stimulates TSH release.
Released in diurnal rhythms
Regulated by various stresses such as starvation and stress.
Active form of thyroid hormone T3 negativity feedback
Feedback control of the control of the thyroid gland?
Role of the thyroid gland?
Regulates the body's energy metabolism
Targets are the brain, muscles, cardiovascular system and reproductive tissues.
Somatotropes?
Proudce growth hormone (GH)
Important for growth and development.
GH has no signal target but liver is major.
Act directly on peripheral tissues and indirectly via
IGF-1 production.
Regulation of GH secretion?
Dual control by hypthoalamus
HP axis stimulates the GH secreion via GHRH.
Inhibits GH secretion via somatostatin.
Somatostatin inhibits GH & TSH release
Feedback control of the Growth hormone?
Pathological conditions involving GH?
Deficiency in Gh produce dwarfism.
Excess causes gigantism (puberty) or acromegaly (in adults)
Difference between gigantism and acromegaly?
Both conditions are mainly due to pituitary tumours.
Excess GH secretion before puberty causes gigantism.
After puberty (ie when body growth stops) causes acromegaly.
ACTH?
Producted in corticotropes in anterior pituitary.
CRH release from hypothalamic neurones stimulates ACTH secretion.
Increase transcription of the POMC gene.
Key regulator of the stress response
(ADD PIC)
ACTH Synthesis
Cleavage of what gene?
POMC gene is cleavaged and produces ACTH.
Give Details of the ACTH
Made up of 39 amino acids
Regulates the adrenal cortex
Synthesis of adrenocorticosterioids
a-MSH resdes in the first 13 amino acids
a-MSH stimulates melanocyres and can darken skin.
ACTH release is stimulated by?
CRH and ADH
Stress
Hypoglycemia
ACTH secretion?
displays a cricadion pattern of release: ie relating to biology variations or rhythms with a cycle of 24hrs.
Highest levels in early AM: depends on sleep-wake cycle.
Secretion of ACTH is also pulsatile (pertaining to an activity characterised).
Regulation of ACTH secretion?
Response to severe stress: hypothalamus can reset the set point of the H-P axis.
Negative feedback on: pituitary and hypthalamus
Cushing's Disease?
Bengin tumour in the pituitary gland
Producing large amounts of ACTH.
Casuing the adrenal glands to produce high levels of cortisol (hormone)
What happens when coritsol secretion is increased?
Causes a tendency to gain weight, centripetal fat distribution and buffalo hump (ie. accumulation of fat on the back of the neck)
Gonadotropes?
Cells in anterior pituitary that produce LH & FSH.
Regulates function of gonads in both sexes.
FSH & LH secretion is regulated by GnRH (gonatrophin-releasing hormone).
Regulation of FSH and LH secretion?
LH: GnRH only.
FSH: GnRH and inhibin
Key features of Cushing's Disease?
Upper body obesity
Moon face
Increased fat around neck
Thinning arms and legs
Bruises easily & heals poorly
High blood pressure
Sever fatigue
Muscle weakness