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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.