Introduction to Endocrine systems and reproduction and the HPA axes Flashcards
Where is the pituitary gland located
Pituitary gland protected
at base of brain in sphenoid bone,
connected by pituitary stalk
Connected by pituitary stalk
(blood vessels transporting
chemical signals to anterior
pituitary gland).
- Anterior pituitary: cup of
tissue around posterior
pituitary. - Optic chiasm: where optic
nerves cross and run along base
of brain. - Pituitary tumours: press on
optic nerve.
Describe the development of the pituitary gland
Anterior pituitary (adenohypophysis): from roof of mouth and
grows up.
o Rathke’s pouch: evagination at roof of mouth in front of
buccopharyngeal membrane. Gives rise to anterior
pituitary (adenohypophysis).
- Posterior pituitary
(neurohypophysis): forms
from neural tissue from
basal floor of
diencephalon and grows
down. Grows to meet an
upgrowth from mouth of
embryo. - There is a cleft between
these 2 tissues in adult
Describe the posterior pituitary
Smaller of 2 lobes.
* Large bodied neurones in hypothalamus send projections down
through pituitary stalk and terminate in posterior pituitary.
* In posterior pituitary, a series of nerve endings release chemical
components in posterior pituitary area where they enter plexus
which has blood coming in via inferior hypophyseal artery and
leaves plexus to body.
- Paraventricular nucleus: sit and line base of 3rd V.
- Supraoptic nucleus: collection of neuronal cell bodies sits to side
of optic chiasma.
What are the hormones from the posterior pituitary
Neurohypophyseal hormones:
o Oxytocin (OT): stimulates smooth muscles.
o Vasopressin (arginine vasopressin) (AVP)/anti-diuretic
hormone (ADH) (same thing). 2 names because it has 2
receptors.
* Synthesised in cell bodies of magnocellular neurones (PVN (paraventricular nucleus) and SON (supra-optic nucleus)).
* Axonal transported from hypothalamus to posterior pituitary.
What are the hormones from the anterior pituitary
Release small peptide hormones which act and are transported
down hypophyseal portal system.]
- Blood vessels are leaky and contain pores which allow uptake
from hypothalamus. - Median eminence: area of fenestrated blood vessels which acts as
a funnel which ship contents of hypothalamus down pituitary stalk
to anterior pituitary cells. - Within anterior pituitary, there is a range of different cell types
determined by a range of transcription factors and each cell
produces just 1 or 2 hormones. - There are specific peptide hormones produced in hypothalamus
which target range of individual cell types in anterior pituitary.
Describe the histology of the adenohypophysis
Bulk of adenohypophysis
in pars distalis.
- That tissue is
composed of
winding cords of
epithelial cells
flanked by
vascular
sinusoids. - In sections
stained with dyes
such as
haematoxylin
and eosin, 3
distinct cell types
are seen among
epithelial cells.
What is the intermediate lobe
Boundary between anterior and posterior lobes.
- Pars intermedia is closely associated with pars nervosa and
separated from pars distalis by hypophyseal cleft (remnant of
Rathke’s pouch). - This lobe of pituitary shows considerable variation in size among
species (small in man but much larger in amphibians). - Melanocyte-stimulating hormone is predominant hormone
secreted.
What are the hypothalamic factors
- Synthesis and secretion of anterior pituitary hormones can be
under dual control of:
o Hypothalamic releasing hormones.
o Hypothalamic inhibitory factors. - Synthesised in parvicellular neurones. Secreted at median
eminence of 3rd V.
What is the dual control of GH secretion
Hypothalamic stimulating
factor GHRH activates GPCR
on anterior pituitary to
produce GH. GH is released.
1 site of action is on liver,
where it induces production
of IGF-1. -ve feedback loop
means production of IGF-1
can ↓ GH in anterior pituitary and inhibit release of GHRH to
regulate amount of GH released into circulation.
- GH is also controlled by somatostatin, which is produced near
GHRH neurones and has a -ve effect on GH production. Couples to
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to ↓ cyclic AMP generation in cell and ↓ intracellular signalling
to reduce GH. There is less -ve feedback on GHRH which produces
GH again. - Advantage of dual control is to give fine control of tuning on and
off systems where tight control of action is required. - External factors affect many endocrine factors. Stress inhibits
GHRH and sees a ↓ in GH output within axis. Outside controllers
can affect this axis. - Rule: anterior pituitary stimulated by hypothalamic releasing
hormones (and may be suppressed by hypothalamic inhibitory
factors). Prolactin appears to be under dominant -ve control by
dopamine (from arcuate nucleus). Stimulation = less inhibition.
What are the levels of negative feedback
Short loop (from anterior pituitary to hypothalamus):
o Effects of LH/FSH on GnRH.
o Effects of GH on GHRH.
* Long loop (from outside hypothalamo-pituitary complex):
o Effects on gonadal steroids on GnRH.
o Effects of corticosteroids on CRH.
How can functional disconnection of the pituitary occur
Cranial trauma: can severe hypothalamus from pituitary. Can
cause hyperprolactinaemia. No posterior pituitary hormones
either.
* Pressure on pituitary stalk: pituitary tumour or inflammation.
* Inflammation/infection: cytokines.
Mid-line defects: septo-optic dysplasia, cleft lips and pallets.
* Defects in migration of hypothalamic neurones: Kallman’s
syndrome.
o GnRH neurones are produced in nasal placodes and
migrate to hypothalamus.
o Neurones in Kallman’s syndrome do not produce right
gonadotrophins (responsible for steroid production, and
hormones are key to fusing long bones).
o Patients are tall, thin, often have deficits in smell and
taste. Prevent completion of puberty.
Describe hypo and hypersecretion of anterior pituitary hormones
Hyposecretion of anterior pituitary hormones
* Adenohypophyseal cells: sensitive to irradiation. Particularly
somatotrophs.
* Hyposecretion of individual anterior pituitary hormones: rare.
Hypersecretion of selected anterior pituitary hormones
* Functional pituitary tumours are rare. Most common is
prolactinomas (become biggest in men). Often identified by visual
field loss rather than endocrine status.
o Galactorrhoea: spontaneous flow of milk from breast
not associated with childbirth or nursing.
o Infertility: prolactin suppression of HPG axis. Postpartum (woman breastfeeding infant does not get
pregnant straight away, this is due to -ve feedback of
prolactin inhibiting HPG axis).
ACTH-hypersecretion:
o From pituitary corticotrophs (Cushing’s disease).
o Ectopic: from small cell lung tumours.
* GH secretion:
o Gigantism: in infancy.
o Acromegaly: in adulthood.
* TSH hypersecretion: (very rare)
o High [TSH] usually reflects hypothyroidism.
o Or assay error.
Why is ectopic ACTH not suppressed by cortisol
Ectopic ACTH (i.e. from tumour cell) is not under control of CRH.
* Ectopic ACTH secretion is not dependent on CRH.
* When a hormone is expressed in ectopic site, normal feedback
regulation by CRH does not occur, leading to excess production.
Describe oxytocin
9 AA peptide that is
synthesised in hypothalamic
neurones in posterior
pituitary.
* Secreted from few other
tissues, including ovaries and
testes.
* Differs from ADH in 2 of 9
amino acids.
Describe the cellular actions of oxytocin
1.1. Stimulation of milk ejection
(milk letdown)
* Milk is initially secreted into
small sacs within mammary
gland called alveoli, from
which it must be ejected for
consumption or storage.
* Mammary alveoli are
surrounded by smooth
muscle (myoepithelial) cells
which are a target cell for
oxytocin.
* Oxytocin stimulates
contraction of myoepithelial
cells, causing milk to be
ejected into ducts and
cisterns.
1.2. Stimulate uterine smooth
muscle contractions at birth
* During later stages of gestation, oxytocin receptors ↑ on uterine
smooth muscle cells, which is associated with ↑ “irritability” of
uterus.
* Oxytocin is released during labour when foetus stimulates cervix
and vagina, and it enhances contraction of uterine smooth muscle
to facilitate parturition.
* In cases where uterine contractions are not sufficient to complete
delivery, oxytocin analogues can be given.
