3rd February 2011
Endocrinology 4
THE PITUITARY GLAND
helen.christian@dpag.ox.ac.uk
Gross anatomy
The pituitary gland is situated beneath the hypothalamus of the brain, in a depression, the ‘pituitary
fossa’, of the skull. The pituitary comprises anterior, intermediate and posterior lobes.
Development of the pituitary gland (or hypophysis)
Rathke's pouch grows up from oropharyngeal ectoderm (roof of the mouth) to form the anterior
pituitary. The infundibular process grows down from the forebrain vesicle to form the posterior
pituitary. The portion of Rathke’s pouch in contact with the posterior pituitary forms the intermediate
lobe. This lobe remains intact in some species but in humans its cells become interspersed with those
of the anterior pituitary.
Vasculature
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posterior pituitary: blood supply direct from internal carotid artery.
hypothalamus: branches direct from internal carotid artery. These form a capillary plexus in
the base of the hypothalamus that gives rise to hypothalamo-hypophysial portal veins which run
down the pituitary stalk to the anterior pituitary.
anterior pituitary: blood supply is from the hypothalamo-hypophysial portal veins.
Anterior pituitary (or adenohypophysis, anterior lobe)
The anterior pituitary consists of numerous individual endocrine cells. There are distinct cell types
which produce and secrete the various hormones termed thyrotrophs, corticotrophs, gonadotrophs,
lactotrophs and somatotrophs. Glial like folliculostellate cells surround and support the endocrine
cells. The different cell types can be identified by immunocytochemistry and by their structural
appearance under the electron microscope.
The anterior pituitary is regulated by
a) neurohormones from the hypothalamus – ‘central control’. Overall hypothalamic control is
stimulatory for all anterior pituitary hormones except PRL (inhibitory). The pulsatile release
of hypothalamic releasing factors stimulate pulses of anterior pituitary hormones.
b) systemic hormones – ‘feedback control’, mainly negative, by target hormones.
c) Paracrine interactions in the anterior pituitary.
Posterior pituitary (or neurohypophysis, neural lobe)
• The posterior pituitary is formed by the axons and terminals of magnocellular neurosecretory
neurons originating in the hypothalamus. Pituicytes (a type of glial supporting cell) surround and
support the terminals. The posterior pituitary hormones are synthesized in the hypothalamus,
packed into granules, transported down the axons and released by exocytosis into the systemic
veins draining the neurohypophysis.
• The posterior pituitary releases the peptide hormones vasopressin and oxytocin, produced from
prohormones.
• Release of hormones from the posterior pituitary is controlled entirely in the hypothalamus.
HORMONES OF THE ANTERIOR PITUITARY
Thyroid Stimulating Hormone = TSH, or thyrotrophin. Secreted by thyrotroph cells.
Chemical nature: glycoprotein hormone made of alpha and beta subunits; the beta subunit is specific
to TSH, the alpha subunit is shared with LH and FSH.
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Receptors: G protein coupled to cAMP, on thyroid gland follicular cells.
Actions: TSH acts in the thyroid: it stimulates thyroid hormone (T3 and T4 – see Thyroid lecture
week 4) production; increases iodine uptake by the thyroid (required for thyroid hormone
production) and stimulates thyroid growth.
Control: TSH release is stimulated by thyrotrophin releasing hormone (TRH) from the
hypothalamus. Secretion of TRH is stimulated by cold and by stress via the CNS. TSH is
released in pulses with a diurnal rhythm.
Systemic control of TSH release: inhibited by T3 & T4 negative feedback.
Dysfunction: TSH disorders are very rare.
Adreno Cortico Trophic Hormone = ACTH or corticotrophin. Secreted by corticotroph cells.
Chemical nature: polypeptide hormone cleaved from the prohormone, ProOpioMelanoCortin
(POMC).
Receptors: G protein coupled to cAMP, in adrenal cortex.
Actions: Stimulates production and therefore secretion of cortisol (glucocorticoid steroid hormone)
from the cortex of the adrenal gland (see Adrenal lecture week 5). ACTH produces some
increase in adrenal sex steroids also and stimulates growth of the adrenal cortex.
Melanocyte-Stimulating Hormones (MSH) is also cleaved from POMC and is released by
corticotrophs. MSH stimulates pigmentation of skin via actions on melanocytes.
Control: Secretion of ACTH is increased by stress. Secretion is pulsatile with a diurnal rhythm
(high at 7.00am, low at midnight). Release of ACTH is stimulated by corticotrophin
releasing hormone (CRH) from the hypothalamus.
Systemic control of ACTH release: inhibited by glucocorticoid negative feedback.
Dysfunction: Excess ACTH from corticotrophinoma pituitary tumours causes excess glucocorticoid
secretion - Cushing's disease; deficiency of ACTH causes glucocorticoid deficiency - Addison's
disease. Nelson's syndrome - increased pigmentation via excess MSH secretion due to lack of
negative feedback actions of cortisol on POMC expression after adrenal cortex surgery.
Gonadotrophins
LH = Luteinizing Hormone, FSH = Follicle-Stimulating Hormone. Secreted by gonadotroph cells.
Chemical nature: glycoprotein hormones made up of an alpha and a beta subunit; the alpha subunit
is common with that in TSH, the beta subunitss are specific to LH and FSH.
Receptors: both are G protein coupled to cAMP in ovary and testes.
Actions:
Female: LH and FSH control growth and development of follicles; ovulation;
synthesis of sex steroids by the ovary; growth and secretion of the sex steroid
progesterone by the corpus luteum. Male: LH controls testosterone production by the
Leydig cells; FSH stimulates the Sertoli cells and sperm production – see Trinity Term
Reproduction lectures.
Control:
Hypothalamic: LH and FSH release is stimulated by hourly pulses of gonadotrophin
releasing hormone (GnRH) during reproductive life.
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Systemic: inhibited by sex steroid oestrogen by negative feedback; however switch to 'positive
feedback' triggers LH surge at ovulation. Cyclical variations in LH and
FSH in menstrual cycle. In males LH release is inhibited by negative feedback
from testosterone; ovarian peptides (inhibin & follistatin) inhibit FSH.
Dysfunction: Deficiencies of LH and FSH or receptor dysfunction as a result of genetic mutations
causes infertility in adult life and lack of sexual maturation in children. Excess LH and FSH secretion
(nearly always due to inappropriate hypothalamic GnRH secretion) or receptor overactivity due to an
activating mutation causes precocious puberty.
Prolactin= PRL, mammotrophin. Secreted by lactotroph cells.
Chemical nature: protein.
Receptor: single-transmembrane tyrosine kinase, in breast.
Actions: Principal role in preparation for lactation. There is a marked increase in the number of PRL
cells in pregnancy, to the extent that the pituitary size nearly doubles. PRL stimulates the
development and growth of secretory alveoli in the breast and milk production. PRL also inhibits
the reproductive system at the level of the gonads and pituitary (causes ‘lactational amenorrhoea’ in
women after delivery of baby- see Trinity Term reproduction lectures).
Control: Secretion of PRL is increased by suckling.
PRL is the only pituitary hormone whose principal control is inhibition by the
hypothalamus. PRL release is inhibited by dopamine from the hypothalamus, PRL
synthesis is stimulated by circulating oestrogen.
Dysfunction: Hypersecretion of PRL can occur from PRL-secreting tumours in the pituitary gland
termed ‘prolactinomas’; causes galactorrhoea, infertility and impotence. Drugs that are dopamine
agonists e.g. bromocryptine are used to suppress PRL release from tumours and are also used to
suppress lactation in women.
Growth hormone = GH or somatotrophin. Secreted by somatotroph cells.
Chemical nature: protein.
Receptor: single-transmembrane tyrosine kinase.
Actions: Stimulates long bone and soft tissue growth, both via stimulating the release of IGFs
(insulin-like growth factors) from the liver and by direct actions. It is essential for growth
after 2 years postnatal but only promotes growth if sufficient nutrition is available. GH also
exerts complex actions on metabolism (amino acid, fatty acid, glucose). GH has insulin-like
effects to promote amino acid uptake by liver and muscle and therefore promotes protein
synthesis. However, if GH is chronically increased it has anti-insulin effects. It is one of
the hormones that switches metabolism away from glucose use and toward increased
oxidation of fat (e.g. in starvation).
Control: GH is secreted in pulses about every 4h, and on entering deep sleep.
Secretion is increased via the hypothalamus by hypoglycaemia, stress and exercise.
Hypothalamic factors that regulate GH release are growth hormone releasing hormone
(GHRH) which stimulates and somatostatin which inhibits GH release.
Systemic control is via negative feedback by GH at the hypothalamus.
Dysfunction: GH insufficiency causes short stature (dwarfism); GH excess causes gigantism in
children, acromegaly in adults.
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HORMONES OF THE POSTERIOR PITUITARY
Antidiuretic hormone = ADH, vasopressin
Chemical nature: peptide of 9 amino acids.
Receptors: acts on V2 receptors in kidney, G protein coupled to cAMP and V1 (PLC-coupled)
receptors in vasculature.
Actions: increases water reabsorption by acting in collecting ducts of kidney (V2) and vascular
pressor effects constricting peripheral arterioles and veins (V1).
Control: osmotic - sensitive to 1% increase from normal plasma OP - 285mOsm. This is sensed by
hypothalamic osmoreceptors. These are also sensitive to decreases in blood volume or pressure.
Dysfunction: diabetes insipidus (hypothalamic and renal types) due, respectively to lack of ADH
production and action.
Oxytocin
Chemical nature: peptide of 9 amino acids.
Receptors: acts on membrane G protein coupled receptors coupled to PLC in breast and uterine
muscle.
Actions: causes contraction of uterine myometrium in childbirth and causes contraction of breast
myoepithelium to eject milk.
Control: stretch of cervix/vagina during parturition - the Ferguson reflex.
suckling - stimulation of the nipple causes the milk ejection reflex.
Dysfunction: deficit may cause prolonged labour. Knockout mice: labour is normal but no milkejection.
ABNORMAL FUNCTION OF THE PITUITARY
Pituitary tumours:
 hormonal effects: hormone-secreting and non-secreting tumours - effects depend on
cell type.
 mechanical effects: effects on vision via pressing on optic chiasm.
Failure of action of pituitary hormones - naturally occurring mutations of the receptors
vasopressin - failure leads to nephrogenic diabetes insipidus.
growth hormone - failure leads to abnormal short stature.
ACTH - not known; receptor failure probably lethal because of role of cortisol in perinatal period.
TSH - failure leads to rare form of cretinism.
LH - failure leads to infertility, constitutive activity leads to precocious puberty.
Syllabus: 14.2 Pituitary
Core learning objectives:
Describe the pituitary gland, its position, parts, development, and vascular supply
For each of the main hormones produced:
know its chemical type; receptors, basic mechanism of action
describe its principal targets, and its actions on the target
describe how release of the hormones is controlled
outline the principal physiological effects of an excess or a deficiency of the hormone.
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