10. Lectures 21, 22, 23 Flashcards
What is the anatomy of the pituitary gland?
Pituitary gland (hypophysis) sits in pocket (sella turcica) of the sphenoid bone below the hypothalamus
Connected to hypothalamus by the infundibulum (pituitary stock)
Pituitary is composed of 2 lines- anterior pituitary gland (adenohypophysis) and posterior pituitary (neurohypophysis)
Slide 1 lecture 21
Study the diagrams of the hypothalamus and pituitary gland on slides 2-4 lecture 21
(Not too hard)
Okay
What is the process with the hypothalamus and posterior pituitary?
Is it the simple or complicated one?
The axons if hypothalamic neurons that originate in the supra optic and paraventricular nuclei pass down the infundibulum and synapse on, and release hormones (vasopressin and oxytocin) into, capillaries within the posterior pituitary
This is the simple one!!
What is the process with the hypothalamus and the anterior pituitary?
Is it the simple or complicated one?
Capillaries in median eminence (hypothalamus and infundibulum junction) recombine to form hypothalamo-hypophyseal portal vessels
Portal vessels pass down the infundibulum and enter the anterior pituitary gland where they drain into anterior pituitary capillaries
Offers local route for blood to be delivered directly from hypothalamus to cells of anterior pituitary
Provides mechanism for hormones of hypothalamus to directly alter the activity of the cells of the anterior pituitary gland and regulate hormone release
This is the complicated one!!
What are the 3 steps of the posterior pituitary hormones?
Posterior pituitary is extension of brain that secreted neurohormones made in hypothalamus
- Paraventricular and supraotpic nuclei both have neurons that synthesize vasopressin and oxytocin
- Hormones are transported down axon and stored in terminals in posterior pituitary
- During neuronal AP firing, stores hormone is released from the terminals into systematic blood for distribution throughout body
Slide 6 Lecture 21
How are hormones secreted by the anterior pituitary gland?
Hypophysiotropic hormones are secreted by neurons that originate in discrete nuclei of the hypothalamus and terminate in the median eminence around the capillaries that are origins of hypothalamo-hypophyseal portal vessels
These vessels carry hypothalamic hormones from median eminence to anterior pituitary gland
They diffuse jug of anterior pituitary capillaries into interstitial fluid around anterior pituitary gland cells
They bind to specific membrane bound receptors and act to stimulate or inhibit secretion of different anterior pituitary gland hormones
Slides 7-9 lecture 21
What is the 3 hormones sequence starting with hypophysiotropic hormone?
- A hypophysiotropic hormone controls the secretion of:
- An anterior pituitary gland hormone, which controls secretion of:
- A hormone from other endocrine glands that then acts on its target cells
Slide 10-11 Lecture 21
What are the 6 main peptide hormones and their targets?
Follicle stimulating hormone (FSH) and luteinizing hormone (LH) act on gonads you release testosterone in males and progesterone in females, also develops ovum and sperm
Growth hormone (GH) stimulates liver to secrete IGF-1 and stimulates other organs for protein synthesis and carb metabolism etc
Thyroid stimulating hormone (TSH) stimulates thyroid to secrete thyroxine
Prolactin stimulates breasts for milk production and breast development
Adrenocorticotropic hormone (ACTH) stimulates adrenal cortex to secrete cortisol
All 6 are peptide hormones
Slide 12-13 lecture 21
What takes control of hypothalamus and anterior pituitary gland?
Hormone feedback
Negative feedback exerted upon the hypothalamo-hypophyseal system by one or more of the hormones in its sequence is effective in dampening hormonal responses- that is, in limiting the extremes of hormone secretory rates
Ex: TRH from hypothalamus stimulates anterior pituitary, TSH from anterior pituitary releases to bloodstream and stimulates secretion if thyroid hormones which stimulates thyroid gland, thyroid gland releases thyroid hormones into blood stream which inhibit anterior pituitary and hypothalamus
Slide 14-15 lecture 21
How are hypophysiotropic hormones controlled by neurons?
Neural control
Neurons of hypothalamus receive stimulating and inhibitory synaptic inout from virtual all areas of central nervous system
Specific neural pathways influence secretion of individual hypophysiotropic hormones
Large # of neurotransmitters like catecholamines and serotonin are relaxed at synapses in hypothalamic neurons that produce hypophysiotropic hormones
Slide 16 lecture 21
How do astrocytes control hypophysiotropic hormone release?
Astrocyte control in a retrograde neuronal-glial-neuronal circuit
Dendritic release of vasopressin stimulates astrocytes, which signal to presynaptic GABA neurons via ATP release.
Upstream GABA neurons respond with action potential risks and GABA release back in to vasopressin neurons
Slide 16 lecture 21
What is the circadian influence over secretion of hypophysiotropic hormones?
Neural inputs from other regions of the hypothalamus, which in turn are linked to inputs from visual pathways that recognize presence or absence of light
Ex: secretion fo CRH is tied to day/night cycle, results in ACTH and cortisol concentrations in blood begin to increase just prior to the waking period
Slide 17 lecture 21
Read through articles slides 1-5 lecture 22
Okay
What are the physiological processes that vary over the 24 hour day?
6am- cortisol release 7am- fastest increase in blood pressure 9am- high alertness 3pm- best coordination, fastest reaction times 6pm- highest body temp 7pm- highest blood pressure 9pm- melatonin secretion 1am- deep sleep 4am- lowest body temp
Slide 7 lecture 22
What are circadian rhythms?
Defined as rhythms that persist with a cycle length of approx 24 hours in constant environmental conditions
Reflect an underlying biological mechanism that can measure time in 24 hour increments
Orchestrated physiology to achieve predictive (rather than reactive) homeostasis
Slides 8-9 lecture 22
What are biological clocks?
Persistence of the rhythms in constant conditions reveals they are true circadian rhythms rather than being generated in response to environmental variation
An intrinsic biological clock mechanism orchestrates physiological processes that vary over the 24 hour day
Slides 10-11 lecture 22
What is the suprachiasmatic nuclei (SCN)?
A biological clock
SCN lesions destroy circadian rhythms
Rhythms can be restored to ablated animals by transplanting a new SCN into the hypothalamus
Circadian rhythms of transplanted SCN were adopted, not the rhythm animals were born with
Each neuron contains a clock
Slides 12-14 lecture 22
How do individual neurons of the suprachiasmatic nuclei keep time?
Action potentials are not necessary for SCN neurons to keep their rhythm
Absence of AP has no effect on rhythmicity of metabolism and biomechanical functions of individual neurons - clock keeps running
Don’t need coordinated rhythmic input from other neurons to generate circadian rhythms of firing rate
Slide 15 lecture 22
How is each SCN neuron made to produce a certain clock mechanism?
Each SCN neuron is a minuscule clock that keeps time with a molecular cycle based on gene expression
Cycle determined by the time it takes to produce a degrade a set of proteins
A clock gene is transcribed to produce mRNA that is then translated into proteins
After delay new manufactured proteins send feedback and interact with transcriptional mechanism, decreasing gene expression, less protein produced (cycle takes around 24h)
Slide 16 lecture 22
What is a critical mechanism for producing circadian rhythms in membrane potential and neuronal firing rate?
Circadian regulation of transcripts encoding ion channels is a critical mechanism for producing circadian rhythms in membrane potential and neuronal firing rate
What is the day and night values (low or high) for these ions: Basal K+ Voltage-dependant Ca2+ Fast-delayed rectifier (FDR) current Ca2+ activated K+
Basal K- day low / night high
Voltage gated Ca- day high / night low
FDR current- day high / night low
Ca activated K- day low / night high
Slide 17-18 lecture 22
Study the importance of fast delayed rectifier potassium currents on input and output of circadian system
Slide 19 lecture 22
Okay
What regulates circadian behavioural rhythms and pacemaker outputs?
BK calcium-activated potassium channels regulate circadian rhythms
Daily expression of BK-potassium channel in SCN is controlled by an intrinsic circadian clock
SCN neurons express greater levels of BK channels at night
Slide 1 lecture 23
What is cell-autonomous time-keeping in the suprachiasmatic nucleus (SCN)?
Dynamic process in which electrical activity and the molecular oscillation of the transcriptional-translational feedback loops (TTFLs) are tightly interlinked
When isolated in culture TTFL of SCN neurons is poorly organized and low amplitude
Cellular interactions increase the stability, coherence, and amplitude of TTFLs and synchronize individual clock cells
Slide 2 lecture 23
How do transcriptional-translational feedback loops (TTFLs) ultimately influence circadian rhythm?
TTFLs orchestrate changes in Na and K conductances and [Ca2+]i that drive the SCN neuron between daytime electrical activity and nocturnal quiescence
Circadian profile of [Ca]i is directed by several mechanisms:
Voltage fred channels activated by electrical firing
Ca release from intracellular stores
Neuropeptide signalling via G protein coupled receptors
Slide 3 lecture 23
What are the 4 mechanisms by which the molecular clock regulates spontaneous neural activity in SCN neurons?
- Ion channel proteins made then transport to membrane through rough ER to golgi then transport to membrane to be removed and degraded. Evidence of rhythmic transcription of several ion channels (L/T Ca, Ca activated K (BK) channels, etc)
- AMPA receptors and K channels shown to be rapidly inserted and removed from membrane in response to physiological stimulation, daily trafficking of ion channels and proteins could be responsible for firing rate rhythms
- Distribution of ion channels in plasma membrane can change from day to night
- Robust circadian rhythms in signalling pathways are robust regulators of ion channels and proteins
Slide 4 lecture 23
What is entrainment of the SCN circadian clock?
Since each SCN is a clock, must be mechanism to coordinate thousands of clocks to transmit message as whole
Light information from the retina serves to reset the clocks in the SCN neurons each day
Entrainment- synchronization of the SCN circadian clock to the daily light:dark cycle
Slide 5-7 lecture 23
Does light have the same effect on the circadian rhythm at any time of the day?
No, the response of the circadian system to light depends strongly on the time of day at which the light exposure occurs
For an animal to entrain a 24hr light:dark cycle light must shift the animals clock each day by an amount equal to the difference between their intrinsic, free-running period and the 24hr period of the lighting cycle
Slide 8-9 lecture 23
What are period genes?
Period genes play a central role in the transcription-translation negative feedback mechanism, which creates the neuron autonomous molecular clock
Slide 9 lecture 23
What do each period 1 (Per1) and period 2 (Per2) clock genes do?
Per1 and Per2 clock genes are important transducers of the effects of light on the molecular clock
Exposure to light at night causes large, transient increase in Per1 and Per2 transcript levels
Per gene expression in SCN is unresponsive to light in daytime (when light exposure doesn’t cause phase shifts)
What would light induced increases in Per1 and Per2 early in the night cause?
What about late in the night?
Light-induced increases in Per1 and Per2 protein early in the night would extend the period of transcriptional inhibition. May be mechanism by which light exposure early in night causes phase delay
Light-induced Per expression late in the night would lead to earlier then normal initiation of Per-mediated inhibition, resulting in an advance of SCN molecular rhythmicity in subsequent cycles
Slides 10-11 lecture 23