The Hypothalamus and the Posterior Pituitary

The classic endocrine glands are defined historically; however any group of cells
that can secrete cytokines, which travels via the blood and affects any other cell,
can also be classified as endocrine cells. These non-classical endocrine glands
include: the brain, heart (ANP), kidney (erythropoietin), liver (insulin growth
factor), adipose tissue (heptin- for satiety and control of body weight) and the GI
tract (CCK) among various other cells.

The principle endocrine gland in the brain is the hypothalamus, which is made up
of nuclei and located just above the pituitary. It regulates through different
nuclei: thirst, hunger, sexual behaviour (appetitive mechanisms), fear and rage
(defence mechanisms), temperature regulation and neuroendocrine control on
the anterior and posterior pituitary including also the biorhythms. A person with
a hypothalamic tumour will among other deficits, experience continual hunger.

The hypothalamus secretes various bioactive peptides, some of which will pass
via the primary plexus into the portal hypophyseal vessel and into the anterior
pituitary, while others end up in the posterior pituitary via neurons which secrete
the peptides. The only two hormones secreted from the posterior pituitary are
arginine vasopressin and oxytocin.

Arginine vasopressin is a peptide, 9 amino acids long with a disulfide bridge

influencing the peptide fold. The pathology involving this hormone displays the
vital role this amino acid plays. People who have diabetes insipidus, whose
receptors do not recognise ADH, pass urine all the time.

Oxytocin is also 9amino acids long, and differs only slightly structurally from
arginine vasopressin. There is only a 2 amino acid difference, and oxytocin also
has a disulfide bond characterizing its shape. However, unlike arginine
vasopressin, this hormone is not vital 2 existences, however is important in
woman especially during labour.

Both enzymes being hydrophilic are secreted as prohormones, much larger in

size than the final peptide hormone. Glycophysin II and I on AVP and oxytocin
respectively, together with the glycopeptides at the end of the prohormone, in
the past were seen to be background sequences, however new ideas are
emerging that these “extra” peptides might actually have a role. These “extra”
peptides together with the signal peptide upstream the hormone sequence are
spliced to form the active hormone.

AVP functions in dehydration and in cases of blood loss. When the body is
deprived of water, through excessive sweating for example, the plasma
osmolality increases. The osmoreceptors situated around the major arteries, for
example the carotids sense this increased osmolality and release AcH. When
there is a decrease in central blood volume, e.g. by a road traffic accident
rupturing the spleen or liver. This causes a decreased blood pressure, resulting
in cranial nerves 9 and 10 to release their constant tonic inhibitory impulses. This
will result in a decreased alpha adrenergic inhibition and the release of AVP from
neurons.

Other factors regulate AVP, including pain or stress. In this case AVP will prepare
the brain and muscles with the perfusion required for flight and fight reactions. In
fever, sweating increases, so does the release of AVP, to help the kidney CD and
thick cortical tubule to become more permeable to water. In fact that is the
reason why urine is more concentrated when a patient is feverish. B adrenergic
agents also increase the concentration of avp by helping to reduce the tonic
inhibition of alpha adrenergic receptors. Estrogens also stimulates AVP, in fact
when oestrogen levels are high, women feel bloated. Stimulatory to AVP are also
opiates, nicotine and prostaglandins.

AVP is inhibited by alpha adrenergic agents. Atrial Naturetic Peptide also inhibits
AVP. ANP allows the kidney to excrete a higher concentration of salt and water in
urine. Ethanol is also another AVP depressor such is hypothermia.

If there is a decreased water intake, or a decreased appetite for salt, the blood
pressure will decrease and the plasma volume will also decrease. This will inhibit
venous return, which will inhibit the secretion of ANP, since a high venous return
is required for this enzyme to be secreted. ANP usually will act on the kidney
directly by increasing the secretion of sodium and water in urine and decreasing
the concentration of rennin, which will decrease plasma volume. The kidney is
also affected indirectly by ANP which decrease aldosterone release. Thus if a low
venous return inhibits ANP, the processes just described will be reversed.

The secondary actions of AVP are hypothermia- why this hormone is shut down
during hypothermia, and why it is switched on in fevers. AVP also facilitates
memory and consolidation and peripheral vasoconstriction.

AVP acts on three receptors: V1a, V1b and V2, all of which are G proteins. V1b
activation will result in an increased calcium concentration in cells which results
in an increased vasoconstriction. Stimulation of the V1B, will also increase
cellular calcium concentrations, ACTH is secreted which is a stimulus to the
pituitary. The V2 receptor, when stimulated will result in an increase in cAMP as
a second messenger. This will make the CD and thick ascending limb more water
permeable. The pathology in nephrogenic diabetes insipidus is this receptor.

Both men and woman have oxytocin production. The stimuli for secretion are
vaginal and breast stimulation and the baby’s cry at birth. The cerebral cortex
will recognise the cry and the paraventricular and supraoptic nuclei are
stimulated to release oxytocin and there is the milk ejaculation reflex. In mothers
who do not produce oxytocin, breast feeding may be difficult.

Oxytocin is also helpful during labour. During pregnancy there is an increase in

the oxytocin receptors. As the uterus grows it will contract at first irregularly but
later on contraction is more frequent. When the baby’s head presses on the
cervix, the cervix and vagina will dilate and nerves are sent to the posterior
pituitary, to secrete more oxytocin, which causes the uterine muscles to contract
more. This is an example of a positive feedback mechanism.

Secondary effects includes, curbing appetite for salt, uterine contractions during
intercourse, contraction if vas deferens during ejaculation. Fever, high
temperatures, pain and loud noise prevent oxytocin release.