Metabolic Endocrinology - Hypothalamo-pituitary
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How is the pituitary controlled?
Controlled by the nervous system via the hypothalamus
Where does the anterior pituitary come from?
Rathke's pouch: outgrowth of the buccal cavity detaches itself and becomes the anterior pituitary
Where does the posterior pituitary come from?
The infundibulum develops from an outgrowth of the neuroectoderm from the floor of the third ventricle. It gives rise to the pituitary stalk, the median eminence, and the posterior pituitary
What is the pituitary enclosed in?
- Enclosed in bone cavity
- Sella Turcica
How is the hypothalamus organized?
Organized into discrete nuclei
How is the hypothalamus connected to the anterior pituitary?
- Nuclei are in close proximity to capillary bed which leads to the portal and a second capillary bed
- Capillary bed in median eminence connected to portal veins then a second capillary bed in anterior pituitary - some retrograde flow of blood to allow hormonal feedback from pituitary to hypothalamus
How is the posterior pituitary stimulated?
- Posterior pituitary is an extension of the hypothalamus. Composed of the nerve ending (axons) of neurons whose cell bodies are located in the hypothalamus
- Hormones (oxytocin and vasopressin) are produced in the cell bodies, packaged into granules which migrate to the ends of the axons located in the posterior pituitary
- Stimulation of neurons in the hypothalamus triggers the release of the hormones from the axon tops located in the posterior pituitary
- The hormones are taken up by capillaries and enter the blood stream
How is the anterior pituitary controlled by the hypothalamus?
- Axon terminals the hypothalamic neurons release hypophysiotropic hormones in the area of the median eminence
- Hormones are taken up by capillary blood vessels
- travel to the anterior pituitary via the portal veinHormones enter the anterior pituitary and trigger the release of a second wave of hormones
- The pituitary hormones enter the blood stream via the venous capillaries
What are hypothalamic nuclei?
Cell bodies of the neurons which produce the hypothalamic hormones
Which nuclei produce oxytocin and vasopressin?
- Supraoptic nuclei
- Paraventricular Nuclei
Where does the hypothalamus receive signals from?
All areas of the brain
How does the hypothalamus receive signals from the brain?
Involves several neurotransmitters (norepinephrine, epinephrine, dopamine, serotonin, and acetylcholine)
How is autonomy of the anterior pituitary indicated?
Some degree of autonomy is indicated by maintenance of very low levels of basal GH, FSH, and LH secretion from the anterior pituitary after surgical disconnection of the hypothalamus from the brain
What releases GH?
What releases PRL?
What releases TSH?
What releases LH and FSH?
What releases ACTH?
What are the characteristics of hormones from the anterior pituitary?
- Short half-life in circulation and fast action
- Hormones bind to receptors of target cells in the anterior pituitary and trigger the release of stored hormone granules
Why is it important to have a renewed stimulus on pituitary?
Because of short half life
What is the major hormone secreted from the pineal gland?
Melatonin is the major hormone secreted by the pineal gland
When does the pineal gland start producing melatonin?
In the evening
When do melatonin levels spike?
In the middle of the night
How is melatonin synthesized?
What does the pineal gland do?
Acts as a link between external photoperiod and internal milieu
How is the pineal gland involved in Circadian rhythms?
- Neural connection with special receptors in the retina
- Other receptors may be present in the body
- May entrain body's biological rhythms to the dark-light cycle
What are some other functions of the pineal gland?
- Induction of sleep
- Depression of reproductive activity, inhibition of ovulation and semen production
- Seasonal fluctuations may affect the timing of breeding, migration, ad hibernation in mammals
What are some other functions of melatonin?
- Antioxidant but supraphysiological levels
- Enhancement of immunity
What is chronotherapy and what are some examples
- Timing of medication, surgery and chemotherapy to maximize effectiveness
- Asthma early AM
- Arthritis late in day
- Breast cancer surgery after ovulation
What are the direction actions of GH?
- Mobilization of energy (anti-insulin like effects)
- Promotion of cell differentiation
What are the indirect actions of GH?
Induction of IGF-1 that promotes cell division and has insulin like effects
What is IGF-1?
- GH dependent
- Produced by the liver and other tissues
- IGF-1 from the liver is released into the blood stream and acts in an endocrine fashion
- In other tissues local production and action in a paracrine or autocrine fashion
What is IGF-2?
- Important in fetal development
- Role in adults less clear
- May act via IGF-1 receptors
How does GH promote growth via IGF-1?
- Important during childhood growth, but less during gestation and for the neonate
- Influenced by the nutritional status of an individual
- Height of GH pulses increase with age with marked rise at puberty - then declines with age
- GH and IGF-1 promote growth of long bones at the epiphyseal plates (proliferation of cartilage cells) Epiphyses fuse at the end of puberty and longitudinal growth ceases
How is GH release regulated?
- Balance between GHRH and somatostatin
- Feedback control by IGF-1 on pituitary and hypothalamus
- Feedback control by GH
What increases somatostatin release?
Glucose and fatty acids increase somatostatin release
When is GH level highest?
Highest levels during the nigth
How does glucose effect GH levels?
- Decrease of GH after glucose intake
- Increase of GH after insulin induced hypoglycemia
How does GH interact with glucocorticoid?
How does GH interact with estrogen?
- Estrogen sensitize somatotrophs to produce GH
- Females have higher levels and an earlier rise in GH at puberty
- Estrogen increases production of GH
How does GH interact with Thyroxin
- Promotes transcription of the GH gene
- Hypothyroid children have stunted growth
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