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Mark Hill's notes

  • Mark Hill's website
  • There are many tissues through the body that are now recognised as also having endocrine function, but there are specific organs with primary endocrine function:
    • Hypothalamus
    • Pituitary gland (intimately related to the hypothalamus via a specific circulation)
  • See his link to the textbook "Endocrinology", which is freely available online

Hormones

Hormone types

  • Amino acid derivatives
    • Relate to adrenal glands
  • Proteins, peptides (long/short amino acid sequences)
    • Relate to hypothalamus and pituitary gland
  • Steroids
    • Receptors found in cytoplasm or nucleus
    • Pass through the
    • Relate to the adrenal glands

Hormone actions

  • Autocrine - acts on cell itself (extracellular fluid)
  • Paracrine - acts on local tissues (extracellular fluid)
  • Endocrine - acts remotely, by secretion into blood stream (endocrine organs are richly vascularised)

Hormone reactions tend to be slower and longer term than neural reactions

Hormone receptors

Hypothalamic pituitary adrenal axis

  • Hypothalamus is at the top, feeding into the pituitary gland, which then acts on the adrenal gland
  • There is a negative feedback loop from the peripheral tissues, back to the hypothalamus and the pituitary gland
  • All related to stress - cortisol has all the metabolic effects related to stress
  • We also have a HP thyroid axis and HP gonad axis (shown on his site)

Hypothalamus

  • Has many nuclei in it, each of which regulates a different function of the body
  • The hypothalamus is wrapped around the 3rd ventricle, and their are nuclei which are clusters of nervous tissue organised for a common function
    • The axons of the neurons run down and release hormones into a specialised region
  • Pituitary gland sits downwards into the sella turcica (bony hole), surrounded by dura
  • The nuclei of the hypothalamus sit above the pituitary gland (hypophysis) and its

Hypophysis

  • Pars distalis (anterior pituitary)
  • Pars intemedias (in between)
  • Pars nervosa (posterior pituitary)

Connect posterior pituitary by a short stalk (infundibulum) to the hypothalamus above it

  • Stalk (infundibulum) has lots of axons running down into the posterior lobe, a releasing area for the neuronal end organs
  • Stalk is surrounded by pars tuberalis, which is highly vascularised

Has two separate embryonic origins, as does the adrenal gland

  • Blood supply to the pituitary is complex
  • Anterior pituitary doesn't receive any direct arterial supply (has a specialised portal circulation from the hypothalamus (which produces the releasing hormones to cause secretion of hormones from the AP) stem through which the neurohormones are released)
  • Linked image from introduction, blood supply
    • Superior hypophyseal artery
    • Inferior hypophyseal artery
    • Long portal vessels
    • Short portal vessels communicating between posterior and anterior pituitary
  • Complex vascular network means we'll find lots of blood vessels/sinuses in histology

Neurohypophsis - posterior pituitary

  • Main cell type: pituitocytes - the equivalent of glial cells (not exactly, but modified)
    • Cytoplasm spread out (stellate), and often in contact with lots of vasculature
    • Remainder of structures are Herring bodies - aggregates of neurosecretory vesicles in the neuronal axons (cell bodies are up in the hypothalamus)
      • Herring bodies commonly next to vascular beds - packed with dark secretory granules under EM. A storage area for potential release at a future time
  • Hormones: oxytocin (pregnancy, smooth muscle relaxation), antidiuretic hormons (acts on kidneys to concentrate urine)
  • Pituitary is the size of a pea (0.5 g). Women who have been pregnant have a larger pituitary than men (1.5 g)

Pars intimedia

  • Specialised region in the midline
  • Colloidal bodies - extracellular colloid aggregates (colourful)
  • Basophils
  • See prac class

Adenohypophysis - anterior pituitary

  • 3 parts: pars distalis (majority; 75% of total pituitary gland!), pars tuberalis, pars intermedia
  • Distalis
    • Made up of parenchyma that secrete the hormones
    • Also CT
    • Endocrine cells, organised into clumps/cords between network of capillaries (irregular in size, leaky)
    • Releases glycoproteins
      • Histological staining (H&E): acidophil cells (red/orange cytoplasm, pale staining nucleus), basophil cells (blue staining cytoplasm, dense/darkly staining nucleophils), chromophobe cells (ghosts/pale cytoplasm, pale nucleus)
      • 65% of cells in anterior pituitary are acidophils (round cell, smaller than basophil): represent somatotrophs (growth hormone) and mammotrophs (prolactin, important in 3rd trimester of pregnancy)
      • Basophils: thyrotrophs (produce TSH), gonadotrophs (produce FSH and LH), corticotrophs (produce ACTH)
        • Pars intimedia:Processes ACTH into a number of fragments
      • Chromophobes: recently degranulated cells (basophils/acidophils - has released its secretions, spent out), also represent stem cells
  • Note many sinusoids with red blood cells inside (larger than typical tissue capillaries, which are only one RBC wide, and are leaky)

Adrenal gland

  • Acted on by ACTH
  • Sits on top of the kidney, as a whitish mass. One associated with each kidney. White appearance is due to lots of adipose packed around the surface of the capsule
  • Occasionally you see smaller adrenal gland buried outside the actual adrenal gland proper.
  • Adrenal gland has a thin fibrous capsule made of dense CT, outside of which is adipose tissue
  • Blood supply comes to the adrenal via the superior, middle and inferior adrenal arteries, which branch before entering the capsule. As they enter the capsule, they form a capillary plexus
    • Capsular artery - cortical arteriole - capillary plexus (zona glomerulosa) - cortical sinusoids (zona fasciculata) - capillary plexus (zona reticularis)
  • Medulla has a different blood supply that runs directly through cortex and forms a separate capillary bed in the medulla
  • Cortex is vital for life and the medulla isn't
  • Outer cortex occupies 90% of the volume, medulla (core) occupies 10%
  • They have different embryonic origins (medulla is neural crest, cortex isn't, see lecture next week)
  • Lots of blood vessels means they're hard to fix and view in histology

Cortex

  1. Capsule
  2. Zona glomerulosa (thin layer, 15% of cortical volume)
  3. Zona fasciculata (thick layer, 75% of cortical volume)
  4. Zona reticularis (thin layer, 10% of cortical volume)

Zona glomerulosa

  • Not influenced by ACTH
  • Gatherings of cells (aggregates) form a glomerulus-like structure with capillaries running around it
  • Secretes mineralocorticoids (regulate minerals in kidney)

Zona fasciculata

  • Influenced by ACTH
  • Secretes glucocorticoids
  • Cells organised in longitudinal cords running from periphery to the medulla
  • Between these cords are wide sinusoids (fenestrated, wide capillaries, very leaky)
  • Cells have a light appearance due to presence of foamy cytoplasms (due to accumulation of lipid in cytoplasm, used for synthesis of steroidal hormones)
  • "Spongiocytes"

Zona reticularis

  • Influenced by ACTH
  • Secretes adrenal androgens
  • Cells are less foamy, large cells in little aggregates, circular/large nucleus
  • Sinusoidal spaces lie between the cells
  • Lie just above the cromaffin cells of medulla

Medulla

  • Looks very different
  • Cells arranged in either strands or clusters with red blood vessels passing through the sinusoidal spaces
  • Lots of capillaries, venules and lymphatic vessels
  • Chromaffin cells take up a dye stained with potassium bichromate
  • Under normal H&E appear blue (basophilic)
  • Cells are equivalent to modified postganglionic neurons (innervated by preganglionic sympathetic nerve fibres that enter the medullary region in CT septa)
  • 2 indistinguishable chromaffin cell types, neural crest in origin:
  1. Adrenaline producing cells - (80%)
  2. Noradrenaline producing cells - (20%)
  • Both basophilic, lots of blood vessels between them
  • Look through his images

PDP's notes

Hormones: are chemical messengers synthesised by cells and released into tissue spaces around blood and lymph capillaries to act on target tissues. All endocrine glands have 1) a rich blood supply 2) no ducts 3) cells arranged in blocks, islets, plates or cords.

Pituitary gland (hypophysis) is suspendedby a stalk from the hypothalamus sitting in a bony fossa, the sella turcica in the base of the skull. Signals from the hypothalamus releasing factors control hormone secretions from the pituitary gland

Adenohypophysis (anterior lobe, pars distalis)

  • Pars distalis (70% of the gland) has 3 main cell types:
    • Acidophils: synthesise GH (somatotrophin) and prolactin. Granules in the cytoplasm stain reddish as a result of an acidophilic dye.
    • Basophils: synthesise FSH, LH, TSH and ACTH. Granules in the cytoplasm stain poorly with H&E as result of a basophilic dye.
    • Chromophobes: can differentiate into acidophils or basophils.
  • Control of hormone secretion: The hypothalamus receives information such as pain, olfaction, visual, etc. These messengers signal the release of hormones that are relayed to the pars distalis via the hypothalamohypophyseal portal vessels for the regulation of its hormonal secretions (cascade).
  • Pars intermedia: has basophilic cells surrounding colloid-filled cysts (Rathke's cysts). The cells synthesise MSH, which disperses melanin granules causing skin pigmentation.

Neurohypophysis (pars nervosa, posterior lobe)

  • Contains many neuroglial cells, (pituicytes), that are invaded by nerve fibres from the hypothalamus. Pituicytes do not secrete hormones but are a supporting structure for terminal nerve fibres arising from the supraoptic (produce ADH) and paraventricular (produce oxytocin) nuclei in the hypothalamus. These nerve go down the hypophyseal stalk to enter the neurohypophysis. The hormones move along the axons. Axonal swellings (Herring bodies) act as storage sites for the neurosecretions. Two hormones are stored and released by the neurohypophysis i.e. vasopressin/ADH and oxytocin.

Adrenal gland (suprarenal)

Here we're concerned with the cortex

  • Capsule: made of collagen surrounds the gland
  • Cortical zones: 3 zones differentiated by the arrangement and morphology of their secretory cells.
  • Zona glomerulosa: beneath the capsule (10-15% of the cortex). It contains columnar cells arranged in round clusters separated by trabeculae containing sinusoids. The cells secrete mineralocorticoids e.g. aldosterone to maintain fluid and electrolyte balances.
  • Zona fasciculata: middle area (75-78% of the cortex) has cuboidal cells arranged in columns, separated by reticular CT septa containing sinusoids. This zone also has large, fat droplets filling the cells.
  • Zona reticularis: inner zone (7-10% of the cortex) consists of branching network of cords of cells amongst sinusoids
  • Zona fasciculata and zona reticularis secrete glucocorticoid hormones e.g. cortisol involved in carbohydrate, protein and fat metabolism. Sex hormones are secreted by the zona reticularis

Adrenal medulla (10% of the gland)

Has chromaffin cells arranged in clusters separated by sinusoids and supported by CT. Features of the medulla are central, medullary veins that drain the adrenal gland. About 80% of the cells synthesise adrenaline and others produce noradrenaline. Release of these hormones into the blood is controlled by the sympathetic nervous system. They include pain, cold, heat, fear, anoxia and other stressful situations.