The hypothalamus and anterior pituitary

The hypothalamus and anterior pituitary

1. The hypothalamus and anterior pituitary

   • Recognises external and internal stimuli and stimulates an appropriate bodily response
     • Stimuli; cold, stress, metabolic demand, dehydration, exercise, time, mestrual cycle, sleep, breastfeeding, puberty, pregnancy/menstrual cycle
       • Responses; adrenal/thyroid/gonadal function, lactation, growth, osmoregulation, parturition and metabolism
   • Structure and connections
     • Hypothalamus
       • Part of the brain (below the thalamus) - major coordination centre for stimuli
     • Anterior pituitary
       • Not part of the brain (embryoinically derived from the oral actoderm)
       • Lies in the pituitary fossa of the sphenoid bone - if it grows it presses n the optic chiasm (visual disturbances seen in pituitary tumours)
       • Not neurally connected to the brain
         • Instead nuclei within the hypothalamus detect a stimulus produce an appropriate releasing hormone (e.g. CRH, TRH, GnRH etc.)
           • These hormone producing neurnes secrete the releasing hormone into a network of cappillaries (neurocrine) called the portal system
             • From here the releasing hormones travel in the blood to the hormone producing cells of the anterio pituitary
               • Releasing hormones stimulate secretion of tropic hormones into a second capillary network which carries the hormones to their target tissues
         • The posterior pituitary develops from the brain and is connected neurally

2. Anterior pituitary hormones

   • Three major families of hormone are produced here
     • POMC family - ACTH (and MSH)
       • Produced by corticotrophs (basophil)
     • Glycoprotein family - TSH, FSH, LH (hCG)
       • TSH: thyrotrophs (basophil)
       • FSH and LH: gonadotrophs (basophil)
     • Somatotropic family - GH and prolactin
       • GH: somatotroph (acidophil)
       • PRL: lactotroph (acidophil)
   • All are regulated by hormones secrted by the hypothalamus into the protal system
     • = hypothalamic releasing hormones and release-inhibiting factors
       • Corticotropin releasing hormone (CRH)
         • Stimulates ACTH release
       • Thyrotropin releasing hormone (TRH)
         • Stimulates TSH release
       • Gonadotropin releasing hormone (GnRH)
         • Stimulates FSH and LH secretion
       • Growth hormone releasing hormone (GHRH)
         • Stimulates GH release
       • Somatostatin
         • Inhibits GH secretion
       • Dopamine (prolactin inhibitory factor, PIF)
         • Inhibits PRL secretion

3. Endocrine axes

   • E.g. Hypothalamo-pituitary-thyroid axis
     • Metabolic demand detected in hypothalamus -> secretes TRH
       • TRH acts on thyrotrophs in the ant. pituitary -> TSH secretion
         • TSH acts on follicular cells in the thyroid -> secrete T4 and active T3
           • T3 acts on target cells to increase metabolism
             • -
           • T4 can be converted to active T3 in the peripheral tissues
             • +
           • T3 and T4 negatively feedback on the hypothalamus and ant. pituitary
             • -
             • -
   • Axes; hypothalamo-pituitary-thyrod/ganadal/adrenal axes and; the GH-IGF axis

4. Prolactin

   • Acts on mammary tissues to stimulate breast development and increase milk production
     • There is no end product from this system to feedback and inhibit PRL secretion
       • Instead PRL is constituitively prodcued by lactotrophs and constantly ready to be secreted
         • To regulate this pathway dopamine (prolactin inhibitory factor, PIF) is constantly being secreted when there is no requirement for milk production
   • Regulation
     • Hypothalamus: Dopamine constantly secreted
       • Lactotrope: Constitutive PRL secretion
         • Breast tissue: milk production
         • +
         • -
           • Dopamine agonists (e.g. Bromocriptine - parkinson's drug)
             • Used in prolactinomas (PRL secreting tumours - the most common pituitary tumour)
       • -
       • -
         • Nipple stimulation (during suckling)
       • -
         • Stress
       • -
         • Dopamine antagonists (e.g. Chlopromazine - antipsychotic)
           • +

5. GH

   • Secretion of GH is under dual control from the hypothalamus
     • Stimulatory: GHRH
     • Inhibitory: Somatostatin (GHIH)
     • Both secretiong control hormones act together to regulate GH levels
     • There is also some negative feedback from IGF-1 (secreted by the liver and bone in response to GH) and by an elevation in blood glucose
       • GH causes an increase in blood glucose
   • GH-IGF axis
     • Hypothalamus: GHRH
       • Ant. Pituitary (somatotroph): GH secretion
         • Bone: IGF-1 secretion
           • IGF-1 promotes linear bone growth
         • Liver: IGF-1 secretion, reduced glucose uptake and gluconeogenesis
           • Tissue growth (e.g. muscle)
           • -
             • IGF-1 and increased blood glucose
       • +
       • +
         • Exercise, sleep, stress, hypoglycaemia
     • Hypothalamus: somatostatin
       • -
   • Actions
     • Mobilises fat stores
     • Opposes insulin and increases blood glucose
     • Stimulates tissue growth (muscle and bone) through IGF-1
       • IGF-1
         • Stimulates growth by....
           • Increasing amino acid uptake
           • Promoting protein synthesis in muscle and cartilage
       • GH is responsible for the linear growth during childhood and puberty
   • Excess
     • In childhood = gigantism
       • Excess long bone growth before puberty
     • In adulthood = acromegaly
       • Large; hands, feet, jaw, brow, internal organs; cardiovascular problems, joint pains and glucose intolerance
     • Testing levels
       • In general
         • Endocrine disorders can be...
           • Primary (gland disorder)
           • Secondary (pituitary disroder)
           • Or tertiary (hypothalamus disorder)
         • Testing of an endocrine axis is important to detemine where the defect is
           • Also to monitor the disorder
       • GH
         • When to take the sample?
           • GH secretion is episodic and daily levels change
             • Etherefore something called dynamic testing is done
               • Dynamic testing
                 • The idea: to challenge the axis and see if the appropriate change occurs
                   • Excess GH
                     • Give IV glucose (take GH level before)
                       • After 1hr check GH level again
                         • GH should have decreased (unless it is being overproduced)
                   • Deficiency (dwarfism)
                     • Have patient excercise (after fasting) - take GH measurement first
                       • After 1hr check GH level again
                         • GH should have increased (unless deficient)
         • Commercial kits available

6. Effects of hypophysectomy (loss or removal of anterior pituitary)

   • Atrophy and functional loss of gonads, thyroid and adrenals
     • Can be treated with hormone replacement therapy (TSH, ACTH, sex steroids and maybe GH, FSH and LH)
   • Signs and symptoms
     • Loss of libido and depression
     • Failure of beard growth
     • Hypotension
     • Hypoglycaemia
     • Testicular atrophy
     • Muscle weakness