Metabolic Endocrinology - Hypothalamo-pituitary

Controlled by the nervous system via the hypothalamus

Rathke's pouch: outgrowth of the buccal cavity detaches itself and becomes the anterior pituitary

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

• Enclosed in bone cavity
• Sella Turcica

Organized into discrete nuclei

• 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

• 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

• 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 vein
• Hormones 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

Cell bodies of the neurons which produce the hypothalamic hormones

• Supraoptic nuclei
• Paraventricular Nuclei

All areas of the brain

Involves several neurotransmitters (norepinephrine, epinephrine, dopamine, serotonin, and acetylcholine)

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

Somatotrophs

Mammotrophs

Thyrotrophs

Gonatogrophs

Corticotrophs

• 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

Because of short half life

Melatonin is the major hormone secreted by the pineal gland

In the evening

In the middle of the night

From tryptophan

Acts as a link between external photoperiod and internal milieu

• 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

• 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

• Antioxidant but supraphysiological levels
• Enhancement of immunity

• Timing of medication, surgery and chemotherapy to maximize effectiveness
• Asthma early AM
• Arthritis late in day
• Breast cancer surgery after ovulation

• Mobilization of energy (anti-insulin like effects)
• Promotion of cell differentiation

Induction of IGF-1 that promotes cell division and has insulin like effects

• 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

• GH-independent
• Important in fetal development
• Role in adults less clear
• May act via IGF-1 receptors

• 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

• Balance between GHRH and somatostatin
• Feedback control by IGF-1 on pituitary and hypothalamus
• Feedback control by GH

Glucose and fatty acids increase somatostatin release

Highest levels during the nigth

• Decrease of GH after glucose intake
• Increase of GH after insulin induced hypoglycemia

Decreases?

• Estrogen sensitize somatotrophs to produce GH
• Females have higher levels and an earlier rise in GH at puberty
• Estrogen increases production of GH

• Promotes transcription of the GH gene 
• Hypothyroid children have stunted growth