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Endocrine Physiology, Hypothalamus, Mechanism, Transmission, Chemical…
Endocrine Physiology
Describe the Functions of Major Hormones
Classes
Hydrophilic
Attracted to water
Peptide hormones
, which are most abundant
Catecholamines
; flight or flight hormones
Indoleamines
, e.g. serotonin and melatonin
Lipophilic
Attracted to lipids
Thyroid hormones
Steroid hormones
How hormones exert their effect on target cell receptors
Endocrine Glands
Hormones
Target Cell Receptors
Tropic Hormones
Regulates the secretion of another hormone from another endocrine gland
Endocrine glands
Hormones
7 Complexities of the Endocrine System
One hormone may have more than one target cell,thus more than one type of action.
E.g. Vasopressin acts on kidney and arterioles
One target cell may be influenced by more than one hormone
E.g. Liver, which is acted on by insulin and glucagon
Some are solely endocrine; others have non-endocrine functions
E.g. Testes
Rate of secretion of hormones may vary over time in a cyclic pattern
E.g. Melatonin, which is peaked at different parts of the day
Some may be hormones and neurotransmitters
E.g. Noradrenaline
One hormone may be secreted by more than one endocrine gland
E.g. Somatostatin, via both the D cells, hypothalamus among others
One endocrine gland may secrete more than one hormone
E.g. Anterior pituitary produces 6 hormones
Effective Plasma Concentration (Blood)
Rate of Hormone Secretion
Most important factor
Control
Negative Feedback Control
“Turning off" the output of a system counteracts a change in inputs
Neuroendocrine reflexes (e.g. “fight or fight")
Circadian/Diurnal rhythm (24h oscillation), or Time based (menstrual). Triggered by
Humoral (change in extracellular fluid)
Hormonal (arrival or removal of hormone)
Neural stimuli (neurotransmitters)
Rate of Metabolic Conversion/Activation
Some hormones are released in inactive form.
Might by adding of chemical groups, metabolic activation.
E.g. Thyroid hormone has 4 iodine. 1 is removed so that it becomes the most potent
Transportation (Extent of binding to plasma proteins)
Refers mostly to lipophilic hormones
Only unbound fractions are biologically active
Hormone Distribution
Hormones may circulate freely or travel bound to special carrier proteins in plasma e.g. thyroxine binding globulin
Free Hormones
Remain functional for less than 1 hour
Thyroid and Steroid Hormones Remain in circulation much longer because most are “bound”
Involved in long term changes e.g. growth/development
Rate of removal by excretion or metabolic inactivation
Hormones need to be inactivated and excreted after asserting their effect.
Hormone Receptors
Protein molecules on target cells that bind to hormone and triggers downstream signalling actions
Different receptors for different hormones
One target organ can have multiple hormone receptors
Presence/absence, receptor expression determine hormonal sensitivity
Response Amplification
Primarily, a bound hormone can lead to an amplified amount of molecules generated
hormone activates 10 activated adenylyl cyclase.
10 activated adenylyl cyclase generates 1,000 cyclic AMP.
1,000 cyclic AMP generates 1,000 activated protein kinase
1,000 activated protein kinase activate 100,000 phosphorylated proteins.
100,000 phosphorylated proteins generate10,000,000 enzymes.
Altering the hormonal response
Upregulation/Downregulation (increasing/decreasing number of receptors)
Locally-acting negative feedback loop leads to desensitization
e.g. Hypersecretion of insulin hormone as a result of eating too much sugar
Target cells are always stimulated
Over time, there will be receptor internalisation
Number of receptors decrease, and reduce sensitivity over time
Blood glucose can't be reduced, leading to diabetes
Hormone interaction
When two hormones act on a target cell at the same time
Antagonistic
: Opposite effect
Progesterone is antagonistic to oestrogen, to facilitate child bearing
Synergistic
: Additive/amplification effect
Permissive
: One is needed for another to produce effect
E.g. Thyroid increases adrenalin receptors
Integrative
: Different but complementary results
E.g. Angiotensin and vasopressin work together to manage blood pressure
Disorders
Hyposecretion
Primary or Secondary (tropic hormone)
Genetic, dietary, toxins, immunologic, disease, iatrogenic, idiopathic
Hypersecretion
Tumors , immunologic (antibody), substance abuse
Abnormal target cell responsiveness
Genetic: e.g. testicular feminization syndrome
Understand & compare the Mechanisms of intercellular communication
Direct Communications
E.g. Cardiac Cells, so that the heart contract synchronously
Gap Junction
Ions, small solutes, lipid-soluble
materials
Usually limited to adjacent cells of the same type
that are interconnected by connexons
Autocrine Communications
E.g. immune system
Through extracellular fluid
Autocrines
Limited to the cell that secretes the hormone
Paracrine Communications
E.g. Somatostatin to influence the secretion of gastrin
Through extracellular fluid
Paracrines
Primarily limited to a local area, where paracrine factor concentrations are relatively high Target cells must have appropriate receptors
Endocrine Communications
E.g. Growth hormone
Through the bloodstream
Hormones
Target cells are primarily in other tissues and organs and must have appropriate receptors
Synaptic Communications
Across synapses
Neurotransmitters
Limited to very specific area; target cells must have
appropriate receptors
Understand the Role of Endocrine System
Endocrine Glands
Ductless glands that secrete blood borne messengers to act on target cells located a long distance away.
More for
duration
, rather than speed.
Main function is to
maintain homeostasis
and
regulate long term processes
Growth
Metabolism
Development
Reproduction
Central
Hypothalamus
Anterior Pituitary (Adenohypophysis)
Most anterior pituitary hormones are tropic
Posterior Pituitary (Neurohypophysis)
Pineal Gland
Hypothalamus
Work with posterior pituitary to secrete vasopressin & oxytocin
Secrete hypothalamic releasing or inhibiting hormones to act on anterior pituitary gland
Control of sympathetic output – neuroendocrine reflex
Neuroendocrine system
Vasopressin (ADH) & Oxytocin are produced by
neurosecretory neurons
in hypothalamus
One hormone can only be produced by one neuron
Axons cross the pituitary stalk
to terminate on capillaries in posterior pituitary
Secretory granules
transport the hormones along axon, then they are stored at
neuronal terminals
Stimulation in the hypothalamus activate action potential, which will then stimulate release of hormones to target cells via venous blood
Posterior Pitutary Gland,
produces ADH and Oxytocin
ADH
Nephrons in kidney
Increases permeability of distal and collecting tubules to water, allowing more water absorbtion
Helps retain water in the body
Arterioles
Vasoconstriction helps to maintain blood pressure
Oxytocin
Uterus
Helps uterine contraction. Neede during childbirth
Mammary glands
Stimulates milk ejection during breastfeeding
Hypothalamic Control
Growth Hormone Releasing Hormone (GHRH)
Stimulates release of GH
Somatostatin (GH Inhibiting hormone) (GHIH)
Inhibits release of GH, TSH
Hypophyseal Portal System
Hormones enter the
hypothalamic capillaries
Hypothalamic capillaries rejoin to form the
hypothalamic–hypophyseal portal system
, a vascular link to the anterior pituitary
1 more item...
Thyrotropin Releasing Hormone (TRH)
Stimulates release of TSH, PRL
Corticotropin Releasing Hormone (CRH)
Stimulates release of ACTH
Gonadotropin Releasing Hormone (GnRH)
Stimulates release of FSH, LH
Prolactin Releasing Peptide (PrRP)
Stimulates release of PRL
Dopamine (PRL Inhibiting hormone) (PIH)
Inhibits release of PRL
Pineal Gland
Tiny, pinecone-shaped structure located in the center of the brain secretes:
Melatonin
Apart from light/dark adjustment, it is also an antioxidant, promotes learning
Master biological clock: SCN
Suprachiasmatic nucleus (SCN)
in hypothalamus above optic chiasm
Self-induced rhythmic firing > fluctuating levels of clock proteins (accumulated to a level, and inhibits its own production)
Synchronisation of biological clock with environmental cues (e.g. light dark cycle)
Light is received via
Melanopsin
Figure 18-13 of Sherwood
Peripheral
Rest of body outside the brain
Hormones
Chemical messengers to relay
information & instructions to cells, aka
signalling
Blood System
Erythropoietin, thromboxane A2, prostaglandins, serotonin, androgen, estrogen
Cardiovascular System
Adrenaline, Noradrenaline
Respiratory System
Angiotensin II, growth hormone, thyroid hormones
Digestive System
CCK, GIP, Secretin, Gastrin, Somatostatin
Metabolic System
Thyroid hormone, testosterone, GH, melanocortins, leptin, insulin, ghrelin,
POMC (Proopiomelanocortin),
ACTH (adrenocorticotropin)
Hypothalamus
Hypophysiotropic Hormone
Anterior Pituitary
Tropic Hormone
Adrenal Cortex
Direct Hormone: Cortisol
Mechanism
Transmission
Chemical Mediators
Distribution of Effects
Secrete
Stimulate or Inhibit
E.g.
FLAT PEG
F
ollicle stimulating hormone (FSH)
L
uteinizing hormone (LH)
A
drenocorticotropic hormone (ACTH)
T
hyroid-stimulating hormone (TSH)
P
rolactin
E
ndorphins
G
rowth hormone (GH)
Functions
secretes
Secretes
acts on
acts on
Negative Feedback
Example
Negative Feedback