Download Hypothalamic Control of Pituitary Function

Hypothalamic Control of Pituitary Function – Dr Miles Levy
It is often said that the pituitary gland is the conductor of the endocrine orchestra.
However the hypothalamus is ultimately in control as it co-ordinates information from
the brain and the external environment and directly influences the pituitary gland via
hypothalamic releasing factors. The supraoptic and paraventricular nuclei directly
innervate the posterior pituitary gland, which is responsible for ADH and oxytocin
production. The arcuate nucleus is the chief hypothalamic structure which secretes
releasing factors to the anterior pituitary. It does this by a unique blood supply called
the hypophysial portal system which transports the hypothalamic releasing factors
from the median eminence to the pituitary gland.
There are five main anterior pituitary axes which include the somatotroph axis, the
adrenal axis, the gonadal axis and the lactotroph axis. Each axis is under negative
feedback control which involves communication in a closed loop between the
hypothalamus, pituitary gland and end organ. Growth hormone is chiefly under
positive control from GHRH and negative control from somatostatin. Other factors
also influence growth hormone secretion including levels of glucose, amino acids and
free fatty acids. Ghrelin is a relatively recently described hypothalamic peptide which
is a growth hormone secretagogue. The adrenal axis is under positive control by CRH
which stimulates corticotrophs to produce ACTH. This system is under negative
feedback from cortisol only and not testosterone or mineralocorticoids. ACTH and
CRH are secreted in a pulsatile fashion, with increased pulses in the morning and
reduced pulses at night. The gonadal axis is under positive control by GnRH which is
secreted in a pulsatile manner. In men, the frequency and amplitude of pulses of
GnRH is low, and levels of LH, FSH and testosterone are relatively stable, with a
simple negative feedback pathway controlling the axis. In women, the frequency of
GnRH pulses is more complex and LH and FSH production from the gonadotrophs
varies with the menstrual cycle, with peak levels occurring at ovulation. Oestrogen
and progesterone are both inhibitory and stimulatory to GnRH depending on the time
in the cycle. The lactotroph axis is the only one under tonic inhibition. Dopamine is
the hypothalamic peptide which inhibits prolactin release and anything which blocks
dopamine transfer to the pituitary gland, either structural or pharmacological, will
cause hyperprolactinaemia. Prolactin is also under weak positive control by TRH,
hence profound primary hypothyroidism can cause hyperprolactinaemia via an
elevated TRH.
The posterior pituitary gland is a neural structure which has a role in lactation,
childbirth and fluid balance. ADH is the hormone which reabsorbs water from the
collecting duct of the kidney and levels are kept under close control by serum
osmolality and thirst. Any process which damages the posterior pituitary gland can
cause diabetes insipidus which can be particularly problematic if the thirst mechanism
is not intact.
Throughout the talk clinical examples are given to highlight how the interpretation of
endocrine results can be achieved through the understanding the basic principles of
the hypothalamic control of the pituitary axis.