The Hypothalamus And Pituitary Gland
Clinical scenario
A 51-year-old man was referred to the Endocrine Clinic as an emergency
complaining of loss of vision in both sides of his visual field. He had been
increasingly tired over the preceding few months, felt ‘sluggish’ and had lost
all motivation for his usual activities. He was shaving less frequently than
normal and had lost some body hair. He had also lost interest in sex, although
put this down to his exhaustion and ‘getting older’. More recently, he felt
dizzy when he got out of bed or stood up from a chair. On examination he had
clinical features of pan- hypopituitarism and examination of his visual fields
revealed a bitemporal hemianopia. Biochemical investigations con- firmed the
presence of hyperprolactinaemia (serum prolactin 35000 mU/L) and suppressed
values of cortisol, thyroxine, TSH, LH, FSH, testosterone and IGF-1. An MRI
scan showed a large pituitary tumour extending superiorly from the pituitary
fossa and compressing the optic chiasm. He was treated with cabergoline, a
long-acting dopamine agonist drug which subsequently caused shrinkage of the
tumour. Examples of pituitary tumours are shown in Fig. 5a.
The hypothalamus
The hypothalamus lies at the base of the brain in the diencephalon. It
contains a number of nuclei of neurones important in the regulation of hormone
secretion from the pituitary. Some of these neurones produce hormones which are
transported in the bloodstream to the pituitary. The hypothalamic boundaries
are arbitrarily defined, in terms of visible structures around it, into the:
rostral or supraoptic hypothalamus; middle or tuberal hypothalamus; and caudal
or mamillary hypothalamus (Fig. 5b). Running longitudinally through the middle
is the narrow third ventricle.
The medial hypothalamus contains a number of nuclei (Fig. 5b), densely
packed with cells, which communicate with the rest of the brain through a
bundle of descending and ascending axons: the medial forebrain bundle.
The lateral zone of the hypothalamus does not have such well-defined nuclei.
The median eminence of the hypothalamus is where the vascular link is
made between the hypothalamic neurosecretory neurones and the pituitary gland.
The pituitary gland
The pituitary gland is distinguished as two main subglands, namely the
anterior and posterior pituitary (Fig. 5b; adenohy-pophysis and
neurohypophysis, respectively). Developmentally, the posterior gland is an
outgrowth of the brain. During fetal development, it arises as a downward
extrusion from the hypothalamus. It is thus neural in origin. The anterior
pituitary grows upwards from the primitive oral cavity, which is termed
Rathke’s pouch. It grows upwards until it fuses with the down-growing
infundibulum, and its cells proliferate around and along the pituitary stalk,
giving rise to the pars tuberalis. During development, a rich vascular
system develops in the median eminence. The up-growth loses contact with the
oral cavity, and the pituitary gland has direct neural contact with the
hypothalamus, through to the posterior pituitary, and a vascular link, called
the portal system, through which chemicals are carried from hypothalamic
cells to the anterior pituitary gland.
Tumours of the pituitary may cause unrestrained hormone release, for
example hyperprolactinaemia (see Clinical scenario and Fig. 5a).
The Nuclei
Supraoptic group of nuclei: the paraventricular (PVN) and
supraoptic (SON) nuclei have axons projecting to the posterior pituitary as the
hypothalamic–hypophyseal tract. The PVN and SON contain large, richly
vascularized cells, which together are termed the magnocellular secretory
system (Fig. 5c). The PVN has other, smaller cells which contribute to a
diffuse collection of hypothalamic neurones called the parvocellular secretory
system (Fig. 5d), which, through the neurohormones it sends to the anterior
pituitary, controls anterior pituitary function. Both the SON and PVN contain
cells which produce and secrete important neuropeptides, for example oxytocin.
The PVN is interconnected with autonomic and other regions of the spinal cord
and the brain stem, as well as with the pituitary gland.
The tuberal or middle group of nuclei are involved in pituitary
regulation. These are the ventromedial, dorsomedial and arcuate nuclei. Like
the PVN, the ventromedial is interconnected with other parts of the brain,
including the spinal cord, the brain stem and the central grey matter of the
midbrain. The arcuate nucleus, which is an autonomous generator of
reproductively important rhythms, sends many axons to the median eminence, as
well as to other parts of the hypothalamus and forebrain.
The mammillary or posterior group of nuclei runs caudally into the
mesencephalic central grey area. Within this area are more magnocellular
neurones which project to many parts of the brain.
The neurohormones
The magnocellular neurones of the SON and the PVN contain neurones which
produce and secrete oxytocin and vasopressin (antidiuretic
hormone, ADH). The hormones are produced in different neurones and are
transported to the posterior pituitary gland via their axons, which comprise
the hypothalamic–hypophyseal tract.
The neurones of the parvocellular neurosecretory system send their axons
to the median eminence, where their terminals release the ‘releasing hormones’:
corticotrophin-releasing hormone (CRH); gonadotrophin-releasing
hormone (GnRH); thyrotrophin-releasing hormone (TRH); and many other
pep- tides, including somatostatin and neurotensin. Other substances emptied
into the portal system include the dynorphins, enkephalins and β-endorphin,
GABA, dopamine and many more substances.
GnRH neurones send axons not only to the median eminence, but to other parts
of the brain, giving rise to the idea that GnRH may be a neurotransmitter as
well as a prime regulator of fertility.
Cells of the PVN parvocellular system are rich in CRH and TRH, and
project to the median eminence. The arcuate nucleus is rich in prolactin
neurones, also called tubero-infundibular dopamine neurones. Arcuate neurones
also contain the peptides galanin and growth hormone releasing hormone (GHRH),
the opioids, somatostatin and several other substances, many of which are transported to the median
eminence and the portal system.
