What is the hypothalamo-pituitary axis?

The hypothalamus is part of the brain that monitors many aspects of the state of the body systems, integrating a large amount of information from many sensory pathways. With regards to the endocrine system it is recognised as being closely linked with the pituitary gland, a small gland hanging from underneath the hypothalamus. There are two parts to the pituitary gland, an anterior part (the adenohypophysis) and a posterior part (the neurohypophysis).

The anterior pituitary

The anterior pituitary contains a number of secretory cells that release hormones, the main ones being:

  • adrenocorticotrophic hormone (ACTH)
  • thyroid stimulating hormone (TSH)
  • growth hormone (GH)
  • follicle stimulating hormone (FSH)
  • luteinising hormone (LH)
  • prolactin (PRL)


These hormones are released in response to stimulation by the appropriate releasing hormones. These are peptide hormones secreted by nerve cells in the hypothalamus. They travel through the portal system of vessels in the pituitary stalk to the secretory cells of the anterior pituitary. There, they cause the production and release of pituitary hormones into the bloodstream.

For Growth Hormone and Prolactin there are also hypothalamic inhibitory hormones which stop their release, providing a control mechanism.

The table below lists the stimulatory and inhibitory hypothalamic releasing hormones for the different anterior pituitary hormones as well as the stimuli for the activation of the systems.

Anterior pituitary hormone Hypothalamic releasing hormone Stimulatory or inhibitory Stimuli for activation of the system
Adrenocorticotrophic hormone (ACTH) Corticotrophin releasing hormone (CRH) Stimulatory Stress (e.g. pain, fever, hypoglycaemia, low BP)
Vasopressin Stimulatory
Thyroid stimulating hormone (TSH) Thyrotrophin releasing hormone (TRH) Stimulatory Rhythmic activity in the hypothalamus
Follicle stimulating hormone (FSH) and Luteinising hormone (LH) Gonadotrophin releasing hormone (GnRH) Stimulatory Rhythmic activity in the hypothalamus
Growth hormone (GH) Growth hormone releasing hormone (GHRH) Stimulatory Exercise, stress, hypoglycaemia, arginine administration, high amino acid levels
Somatostatin Inhibitory
Prolactin (PRL) Dopamine Inhibitory Sleep, stress, suckling stimulus
Thyrotrophin releasing hormone (TRH) Stimulatory


For all the anterior pituitary hormones (except Prolactin), negative feedback plays a major role in controlling their release. The pituitary hormones have an inhibitory effect on the stimulatory hypothalamic releasing hormones. In addition, most of the pituitary hormones induce the production of other hormones from their target tissues. These hormones have an inhibitory effect on the pituitary and the hypothalamus, thereby preventing uncontrolled release of the pituitary hormones.

This system is known as the parvicellular system.

The parvicellular system

Illustration of the parvicellular system - click to enlarge

The diagrams below illustrate the three main axes involving the hypothalamus and pituitary: the hypothalamo-pituitary-adrenal axis (HPA axis) the hypothalamo-pituitary-thyroid axis (HPT) and the hypothalamo-pituitary-gonadal axis (HPG axis).

HPT axis (left)      HPG axis (right)

HPT axis (left) and HPG axis (right) - click to enlarge

What are endocrine rhythms?

The release of the hypothalamic releasing hormones is governed by neural stimuli, as these hormones are actually produced by neurones. Their release often follows a periodic rhythm, such that the blood levels of hormones dependent on these releasing hormones fluctuate throughout the day. Some of these rhythms appear to be intrinsic, independent of the environment. Others appear to be linked to the 24-hour day, so called circadian rhythms. An example of the daily pattern of cortisol is given below, a pattern which is generated by the rhythmic release of CRH which causes a rhythmic release of ACTH, which in turn causes a rhythmic release of cortisol.

Cortisol levels

Click to enlarge

Much research is focused on finding the 'biological clock' that sets up these rhythms. At the moment evidence points to a brain region called the suprachiasmatic nucleus (SCN) being the seat of this rhythmic activity.

The posterior pituitary

This part of the pituitary secretes two main hormones:

  • oxytocin
  • vasopressin (also known as anti-diuretic hormone, ADH).


Nerves originating in the supraoptic nuclei and the paraventricular nuclei of the hypothalamus produce oxytocin and vasopressin. These hormones are transported down the nerve cells to the posterior pituitary where they are then released into the bloodstream to affect their target organs. This is known as the magnocellular system.

Diagram of neurohypophysis

Diagram of neurohypophysis - click to enlarge

The specific stimuli for oxytocin and vasopressin release are illustrated below:

Specific stimuli for oxytocin and vasopressin

Click to enlarge