Hypothalamus-Pituitary Axis* Flashcards
What is the main function of the hypothalamus/pituitary axis ?
The hypothalamus/pituitary axis is the neurocrine/endocrine junction and the system that allows neuronal control of endocrine function.
Describe anatomical location of the hypothalamus.
The hypothalamus is a small region of the diencephalon that is found at the base of the brain, below the third ventricle, where discrete groups of cell bodies exist within anatomically distinct regions or “nuclei
Describe anatomical location of the pituitary.
-Suspended from the hypothalamus by a thin piece of tissue called the “infundibulum” or “connecting stalk” is the pituitary (specifically posterior pituitary connected to stalk) (hypoT and pituitary also linked via median eminence)
-Enclosed by the bony
sella turcica of the sphenoid
- Enclosed superiorly by the diaphragma sellae
- Related to the cavernous sinus
- Lies immediately posterior to the optic chiasma and sphenoid sinus
State the function of the anterior, and posterior lobe of the pituitary.
Anterior lobe comprises endocrine cells which synthesise, store and secrete various protein and polypeptide hormones (GH, TSH, ACTH, LH, FSH and PRL) that enter the systemic bloodstream
Posterior lobe
How does the posterior lobe of the pituitary arise ?
Posterior lobe is the result of swellings of the axonal terminals of neurosecretory cells arising within the hypothalamus
What distinguishes endocrine glands from other glands ?
Endocrine glands have no ducts
Distinguish between endocrine, paracrine, and autocrine secretions.
- Some hormones diffuse directly into capillaries to act on distant target organs (endocrine secretion)
- Others are secreted and act more locally (paracrine secretion)
- Still others act on themselves (autocrine secretions)
How are hormones distributed their site of action ?
Endocrine glands are very vascular: hormones enter bloodstream through fenestrated capillaries.
Are endocrine glands organs, tissues ?
- Some are discrete organs (thyroid, pituitary, adrenals)
- Others are associated with other tissues (e.g. pancreas)
- Others are scattered within complex organs (ovary, kidney, gut)
Where is the thyroid gland located ?
On ventral aspect of trachea
Where are the parathyroid glands found ?
Embedded in the thyroid gland
What is the function of thymus gland ?
Involved in regulating maturation of some lymphocytes through hormones released.
Where is the pancreas found ?
In the loop of the duodenum
Identify the main factors controlling hormone release from endocrine glands.
1) Humoral (endocrine gland responses to extracellular metabolite or factor in blood)
2) Neural
3) Hormonal
Give an example of humoral factor controlling hormone release.
Capillary blood contains low concentrations of Calcium ions, which stimulates secretion of parathyroid hormone (PTH) by parathyroid glands.
Give an example of neural factor controlling hormone release.
Pre-ganglionic SNS fiber stimulates adrenal medulla cells to secrete catecholamines.
Give an example of hormonal factor controlling hormone release.
Hypothalamus secretes hormones that stimulate the anterior pituitary gland to secrete hormones that stimulate other endocrine glands to secrete hormones
Identify the main hormones produced by the adrenal gland.
CORTEX: Steroids, including gluco and mineralocorticoids
MEDULLA: Catecholamines
Identify the main hormones produced by the thyroid gland.
Thyroid hormones, Calcitonin
Identify the main hormones produced by the parathyroid glands.
Parathyroid hormone, PTH
Identify the main hormones produced by the pancreas glands.
Insulin, glucagon, pancreatic polypeptide, somatostatin
Identify the main hormones produced by the GI.
CCK, GIP, gastrin, secretin, VIP, subs. P
Identify the main hormones produced by the thymus.
Thymopoietin
Identify the main hormones produced by the gonads.
Sex steroids, inhibins, acMvins
Identify the main hormones produced by the heart.
Natriuretic peptides, ANP, BNP
Identify the main hormones produced by the liver.
Insulin-like growth factors, leptin, angiotensinogen
Identify the main hormones produced by the kidney.
Erythropoietin, renin
Identify the main hormones produced by adipose tissue.
Leptin
State another name for the pituitary. for the anterior pituitary. for the posterior pituitary.
PITUITARY = Hypophysis
POSTERIOR PITUITARY = Posterior lobe = Neurohypophysis
ANTERIOR PITUITARY = Anterior lobe = Adenohypophysis
Define pars anterior.
-pars anterior (distalis): This is the portion in which the majority of the hormone production occurs. It is the distal part of the pituitary and forms the majority adenohypophysis.
Define pars tuberalis.
-pars tuberalis (PT): this is a tubular sheath that extends from the pars distalis and winds around the pituitary stalk. Epithelial cells arranged in cords and hypophyseal portal vessels reside in this space.
Define pars intermedia (including location and cells present). What is its embryological origin ?
-pars intermedia:
• lies between and anterior and the posterior lobes of the
pituitary
• may contain colloid-filled, epithelial lined follicles
• is poorly developed in humans
Derived from Rathke’s pouch (upgrowth from roof of mouth)
Distinguish between the embryological origin of the anterior, and posterior pituitary.
Anterior: upgrowth of epithelial tissue from roof of the mouth (Rathkhe’s pouch AKA hypophyseal diverticulum)
Posterior and stalk: downgrowth from developing brain (neuronal tissue) (specifically from neurohypophyseal diverticulum)
Anterior lobe then atrophies, and intermediate lobe fuses to posterior pituitary,
What is the function of the pars intermedia ?
• function is obscure.
• Contains numerous basophilic cells, so there may be some
connection with the secretion of melanocyte stimulating hormone MSH (causing skin color changes that are seasonal, in some animals)
Identify the main types of cells present in the anterior pituitary. What is the basis of this classification ?
• Initially the secretory cells of the anterior pituitary were classified according to how they stain with specific dyes:
- Chromophils take up the stain and are of two types:
(A) Acidophils
(B) Basophils
- Chromophobes do not take up the stain (C) (may be acidophils or basophils which have lost their hormones)
What proportion of cells in the anterior pituitary are acidophils ? What is their role ?
65%
Synthesise GH and prolactin
What proportion of cells in the anterior pituitary are basophils ? What is their role ?
35%
Contain other hormones (including TSH, ACTH, LH, FSH, MSH)
Describe the hypothalamo-pituitary axis.
- Superchiasmatic, preoptic, paraventricular, dorsomedial, posterior, ventromedial, supraoptic, arcuate, infundibular nuclei are all nuclei present in hypothalamus. They contain specialised neurons which are neurosecretory cells. Some of these nuclei are larger than others.
- Large cell-bodied neurosecretory cells - mainly exist in paraventricular and supraoptic nuclei (and infundibular nucleus to lower extent). They have long axons that pass down through hypothalamus into the pituitary stalk. They form a nerve tract coming down stalk, called hypothalamo-hypophyeal nerve tract. From the stalk, they enter the posterior pituitary where axonal terminals juxtapose a capillary network (fenestrated capillaries). Neurohormones are therefore synthesised in nuclei in the hypoT, and are then released into the posterior pituitary capillary network which is fed by the inferior hypophyseal artery.
- Within the infundibulum and base of the hypothalamus (the median eminence) a capillary network known as the primary capillary plexus and supplied by the superior hypophyseal artery is innervated with numerous axonal endings arising from small cell-bodied neurosecretory cells located in distinct regions within the hypothalamus. Neurohormones released into this capillary network are collected by a venous drainage known as the hypothalamo-hypophyseal portal system that directs the blood flow to a second capillary network within the anterior lobe or adenohypophysis (anterior pituitary) where the neurohormones regulate the activity and hormonal secretions from the adenohypophyseal cells.
- Secretions of these neurohormones or the hormones from the anterior pituitary are carried by the blood to distant target cells within various organs of the body to induce changes in the biochemical and physiological characteristics of these cells and therefore regulate a wide range of body functions.
Explain how higher brain centers can increase neurohormone synthesis.
• Higher centres within the brain regulate the rhythmical activity of the hypothalamic cell bodies controlling the release of their neurohormones either at the primary capillary plexus in the infundibulum or within the posterior pituitary. Increases in the phasic depolarisations of these hypothalamic neurosecretory cells result in increases in the mean concentrations of cytosolic calcium which stimulates neurohormone synthesis in the rough endoplasmic reticulum, vesicle trafficking from the cell body to axonal terminals and the release of neurohormone from the axonal terminals by exocytosis.
Identify the main hormones of the anterior pituitary.
ACTH TSH LH FSH GH Prolactin
Identify the main hormones of the posterior pituitary.
ADH
Oxytocin (OT)
Identify the neurohormones which control the secretions from the anterior pituitary.
• Thyrotropin-releasing hormone (TRH)
• Corticotropin-releasing hormone (CRH)
• Growth hormone-releasing hormone (GHRH)
(AKA Somatotropin-releasing hormone (SRH)
• Somatostatin/Growth hormone release-inhibiting hormone (SS/ GHRIH)
• Gonadotropin-releasing hormone (GnRH)
(AKA Follicle-stimulating hormone releasing hormone - FSH-RH)
(AKA Luteinising hormone releasing hormone - LH-RH)
• Prolactin releasing factor (PRF)
• Prolactin release inhibiting factor (PIF) = Dopamine
Identify the neurohormones which control the secretions from the posterior pituitary.
Vasopressin (VP) / Anti-diuretic peptide
Oxytocin (OT)
Where are neurohormones released from posterior pituitary synthesised ?
In large cell-bodied nuclei
Define trophic hormone. Identify the main trophic hormone of the anterior pituitary.
Hormone that has a growth effect, hyperplasia or hypertrophy, on the tissue it is stimulating (primary actions on other endocrine glands)
- Thyrotropin/ Thyroid-stimulating hormone (TSH)
- Corticotropin/Adrenocorticotropic hormone (ACTH)
- Gonadotropins (LH and FSH)
What kind of cells produce TSH ?
Thyrotrophs
What kind of cells produce ACTH ?
Corticotrophs
What kind of cells produce gonadotrophins ?
Gonadotrophs
What are the main cells of the anterior pituitary ?
- Somatotrophs -50%
- Lactotrophs or mammotrophs -20%
- Corticotrophs -20%
- Gonadotrophs -5%
- Thyrotrophs -5%
Identify the main hormones of the anterior pituitary which act on peripheral target cells.
Somatotropin / Growth hormone (GH)
Prolactin (PL)
α, β and γ Melanotropin / Melanocyte-stimulating hormone (MSH)
What kind of cells produce Somatotropin/GH ?
Somatotrophs
What kind of cells produce PL ?
Lactotrophs or mammotrophs
What kind of cells produce MSH ?
Melanotrophs
Identify hormones of the hypothalamo-pituitary axis which have precursors.
ACTH (pro-opiomelanocortin -POMC)
MSH (pro-opiomelanocortin -POMC)
Describe mechanisms controlling GH release.
- Neurosecretory cells in the arcuate nucleus secrete GNRH which reaches the somatotrophs via hypophyseal portal blood supply.
- Cells in periventricular region (small cell bodied nuclei) release somatostatin, a hormone that is a potent inhibitor of GH secretion, into the portal blood supply.
- GNRH causes somatotrophs to synthesize and release GH.
- Somatostatin inhibits the release of GH by somatotrophs.
(both GNRH and Somatostatin bind to G protein coupled receptors, but different ones)
Describe feedback from GH release.
GH stimulates secretion of IGF-1 (insulin-like growth factor-1) from peripheral target tissue (binds to GH receptors in liver, which is coupled to synthesis and release of IGF-1)
IGF-1 then directly inhibits GH release by suppressing the somatotrophs (somtotrophs have receptors for both GH and IGF-1)
IGF-1 indirectly inhibits GH release by suppressing GNRH release from the arcuate nucleus in the hypoT (suppress phasic depolarisation of this group of cells)
IGF-1 indirectly inhibits GH release by increasing secretions of somatostatin from nuclei in the periventricular region (increases phasic depolarisation of this group of cells)
GH inhibits its own secretion via short loop feedback on somatotrophs (autocrine signaling)
To what extent is the release of GH constant over time ?
Not constant, PULSATILE (just as almost every hormone coming from pituitary),
In addition to this circadian rhythm affects release of pituitary hormones, including GH (during the night, peaks of GH release are much higher)
Identify a hormone besides GH whose release also follows circadian rhythms.
ACTH
Identify the main physiological actions of GH.
1) Direct Anti-Insulin Effect
-Increased lipolysis in adipose tissue
-Increased blood glucose
(both due to decreased glucose uptake in muscle and adipose tissue, antagonised by insulin release)
2) Indirect actions (IGF-1 release from liver)
- Increased cartilage formation and bone growth
- Increased general protein synthesis and cell growth/division
3) Physiological consequences
- Increased linear growth and lean body mass
- Important for post-natal development and rapid growth through puberty
- Maintenance of protein synthesis and tissue functions in adults
What is the normal function of insulin ? As a result, what does disruption in insulin function result in ?
Stimulates lipid synthesis (no effect on lipolysis) which helps maintain balance between lipid synthesis and lipolysis.
Stimulates recruitment of glucose carriers into membrane of muscle, allowing muscle to be permeable to glucose (so can take it up and metabolise it)
HENCE, when no insulin, lipolysis becomes increased, and blood glucose increaseds
Identify pathologies associated with GH.
1) GH deficiency- Dwarfism
2) GH excess- Acromegaly (before puberty results in gigantism, after puberty results in other features)
Why does GH deficiency result in Dwarfism ? Identify any treatments for this.
• Dwarfism in children due to predictable effects (of lack of GH) on linear bone growth and decreased availability of lipids and glucose for energy
(CAN BE TREATED EFFECTIVELY WITH HUMAN GROWTH HORMONE)
What are the main causes of GH excess ?
Often due to pituitary adenoma
How does GH excess result in gigantism (before puberty) ?
Gigantism occurs due to excess stimulation of epiphyseal plates
What are the clinical features that GH excess results in post-puberty ?
• No stimulation of linear growth due to fusion of epiphyses
• Periosteal bone growth causing enlarged hand, jaw and foot size
• Soft tissue growth leading to enlargement of the tongue and coarsening of facial
features
• Insulin resistance and glucose intolerance (diabetes) (because pancreatic B cells can compensate for anti-insulin effects initially by releasing more insulin, but eventually they get exhausted and cannot produce enough insulin to maintain glucose at adequate level)
Identify any treatments for acromegaly.
Synthetic long-acting somatostatin (e.g. Octreotide) with varying success (depends on whether the adenoma is sensitive to somatostatin)
What are the physical signs of gigantism/acromegaly, besides linear growth (gigantism), enlargement of the jaw/hand/feet, and soft tissue enlargement (i.e. enlargement of tongue and coarsening of facial features) ?
- Skin tags (wart-like growths)
- Muscle weakness/fatigue
- Skin changes, including thickening, oiliness, acne
- Hirsutism (abnormal/unusual hair growth)
Which anterior pituitary hormone is each of the following linked with ?
- GnRH
- GNRH
- SS
- TRH
- DA
- CRH
Identify the effects of each anterior pituitary hormones named.
Refer to slide 23.
Identify factors and hormones which contribute to regulation of prolactin levels.
-Prolactin inhibited by dopamine
Background level of TRH required to maintain prolactin levels in lactating female
Describe cellular processing of the hypothalamic neurohypophyseal hormones for ADH and OT.
All synthesised form larger precursor protein
1) ADH
- Signal peptide cleaved off early in synthesis, leaving prohormone
- Prohormone processed in Golgi Apparatus, and cleaved leaving ADH, Neurophysin II, and a Glycopeptide which are all packed into secretory vesicle
- Glycopeptide quickly degraded
- Neurophysin II acts as binding protein for ADH “as it is carried in axons to the posterior pituitary” (prevents it getting broken down by enzymes)
- ADH will dissociated from Neurophysin II in systemic circulation and will reach its target tissue
2) Oxtocin
- Precursor protein
- Signal peptide cleaved off early in synthesis, leaving prohormone (amino terminal has active peptide)
- Prohormone processed in Golgi Apparatus, and cleaved leaving OT, and Neurophysin I, which are packed into secretory vesicle
- Neurophysin I acts as binding protein for OT “as it is carried in axons to the posterior pituitary” (prevents it getting broken down by enzymes)
- OT will dissociated from Neurophysin I in systemic circulation and will reach its target tissue
Identify the main triggers for ADH release.
Increased blood osmolality, sensed by osmoreceptors (brain)
Decreased BV (sensed by volume receptors in the carotid body, aorta, and L atrium)
RAAS system (e.g. due to drop in BP, or increased sympathetic drive) (leading to angiotensin II release which stimulates ADH release)
What are the main physiological effects of ADH release ?
Recruitment of AQP water channels / water retention (in kidney collecting tubule)
Identify any pathologies associated with deficiency in ADH. How may such a deficiency arise ?
Deficiency- Diabetes Insipidus
Two main causes:
- Cranial (30% tumours causing damage to cells that release ADH, 30% trauma or disease induced possibly causing atrophy to cells releasing ADH, 30% familial disorders of Neurosecretory cells)
- Nephrogenic - sex-linked genetic defect in collecting tubule (inability of ADH receptor to function or mutation in water channel so cannot find its way to the membrane)
What are the main clinical features of Diabetes Insipidus ?
Polyuria, polydipsia
Where in the hypoT is ADH synthesised ?
Synthesised in neurosecretory cells within the supra-optic nucleus (SON) and paraventricular nucleus (PVN)
Where is Oxytocin produced ?
Synthesised in neurosecretory cells within the supra-optic nucleus (SON) and paraventricular nucleus (PVN)
Where in the posterior pituitary is Oxytocin stored ?
Stored in vesicles in the expanded ends of the axons AKA the Herring bodies (not all NS cells have them, but Oxytocin secreting cells do contain them)
What dictates neurosecretion ?
Controlled directly by nervous impulses from the hypoT
Identify a clinical scenario where a large quantity of Oxytocin is released.
In uterus, as baby gets larger, increase in stretch of myometrium is sensed by afferents through spinal cord, into higher centers. As baby get larger, more signals, until it stimulates oxytocin release from SON and PVN.
Herring bodies have extra oxytocin stored, which also gets released.
Oxytocin binds to receptors in the smooth muscle of the myometrium in the uterus, and causes it to contract to help expel the baby at parturition.
Describe hypothalamic control of milk production and ejection.
- Stimulus from suckling travels from breast, through spinal cord to the hypoT
- Neurons from the spinal cord inhibit dopamine (DA) release from arcuate nucleus. Decreased level of DA removes inhibition that DA normally produces on lactotrophs in the anterior pituitary, leading to prolactin release. Prolactin stimulates milk production in the breast
- Neurons from spinal cord also stimulate the production and release of oxytocin from the paraventricular and supraoptic nuclei. Oxytocin is released in the posterior pituitary and into the systemic blood, where it then makes its way to the breast and myoepithelial cells
- Neurons from spinal cord inhibit neurons in the arcuate nucleus and the preoptic area of the hypoT, causing a fall in the GnRH production. The reduced stimulation of gonadrotrophs inhibits the ovarian cycle
Describe anatomical location of the pineal gland.
- Lies in the midline in the posterior part of the roof of the IIIrd ventricle
- Pinealocytes have neural connections with the hypothalamus
Describe role of pineal gland.
- In darkness (not sleep) the pineal secretes melatonin (from tryptophan)
- Regulates circadian rhythms (melatonin has an hypnotic effect)
- Regulates reproductive processes including the onset of puberty in humans
- Effects on aging and regulation of the immune system
Describe effect of aging on the pineal gland.
Accumulates calcium phosphate with time (‘brain sand’ visible in the mid
line on X rays and other scans)
