Considered the conductor of the endocrine orchestra, the pituitary gland acts as a higher level of control in endocrine physiology, regulating the function of several other endocrine organs.
The pituitary gland consists of two lobes – the anterior and posterior pituitary. Differing in embryological origin and histology, these effectively function as two separate endocrine glands.
The table below provides an overview of the hormones secreted from the anterior and posterior pituitary.
|Anterior Pituitary||Posterior Pituitary|
|Growth Hormone (GH)||Antidiuretic Hormone (ADH)|
|Thyroid Stimulating Hormone (TSH)||Oxytocin|
|Follicle Stimulating Hormone (FSH)|
|Luteinising Hormone (LH)|
|Adrenocorticotrophic Hormone (ACTH)|
The remainder of this article focuses on the anterior pituitary.
Overview of Axes
The hypothalamus releases hormones, which stimulate or inhibit the secretion of anterior pituitary hormones. The anterior pituitary hormones have a subsequent trophic (“feeding”) effect on a further endocrine organ in the body, stimulating it to release a final hormone in the pathway, known as the peripheral hormone. This peripheral hormone travels in the blood stream to exert metabolic actions at a variety of tissues in the body.
The rise in levels of this peripheral hormone will usually have a positive and/or negative feedback effect on the pituitary and hypothalamus i.e. will stimulate or inhibit the further release of the respective hypothalamic and/or pituitary hormones. This circuit between the hypothalamus, anterior pituitary and an endocrine gland is known as an axis. A general framework for an axis is depicted below:
Note that in some cases, the anterior pituitary hormone itself may be the peripheral hormone in the pathway or may act on tissues in addition to stimulating a target endocrine gland to release the peripheral hormone.
There are 5 anterior pituitary axes summarised below:
Involving Adrenocorticotrophic Hormone (ACTH)
Growth Hormone Axis
Involving Growth Hormone (GH)
Involving Thyroid Stimulating Hormone (TSH)
Involving Follicle Stimulating Hormone (FSH) and Luteinising Hormone (LH)
Involving Prolactin (PRL)
We will now explore each axis in more detail.
Growth Hormone Axis
The hypothalamus secretes Growth Hormone Releasing Hormone (GHRH). GHRH stimulates somatotroph cells of the anterior pituitary to release Growth Hormone (GH), also known as somatotropin. To exert several metabolic effects in many tissues of the body, GH has direct actions on tissues by binding to cells, and has indirect effects whereby it stimulates the liver to produce Insulin-like Growth Factor-1 (IGF-1) to mediate actions.
The direct actions of GH include:
- Increased lipolysis
- Reduced glucose oxidation
- Reduced protein oxidation.
The effects of GH via IGF-1 can be thought of as “anabolic” (compound building) like insulin and include:
- Increases protein synthesis.
- Increases carbohydrate oxidation
The overall effects, arising from an interplay between the two substances, are important for the following:
- Skeletal growth
- Muscle strength
- Bone density
- Cardiac function
Several factors including stress, exercise, nutrition and sleep modulate the production of growth hormone. Whilst GHRH promotes GH release, Somatostatin, produced by the hypothalamus, the intestines and delta cells of the endocrine pancreas, inhibits GH.
The figure below summarises the Growth Hormone Axis:
There is also inhibition of GH production by IGF-1, which prevents somatotroph releasing GH and promotes somatostatin release from the hypothalamus.
Clinical Relevance – GH Deficiency
In children, a deficiency of GH would result in a short stature due to slow bone and muscle maturation and delayed puberty. In adults, changes are more subtle and include:
- Reduced muscle mass and strength
- Reduced bone mass
- Reduced energy
- Possible cardiac dysfunction
One famous example of Growth Hormone deficiency is that of Lionel Messi. The future Ballon d’Or winner moved to FC Barcelona at the age of 13, as the club promised to fund his treatment of the condition.
Clinical Relevance – GH Excess
In adults, an excess of GH is called Acromegaly and is often caused by a pituitary tumour secreting GH.
Clinical features include:
- Large extremities and growth of hands and feet
- Coarse facial features, and rounded face
- Pronounced jaw
- Enlarged heart
In children, hypersecretion of GH results in gigantism, where the child grows very tall. Treatment involves surgery to remove the tumour, via the sphenoid bone (“transsphenoidal”) if the tumour is large enough, or medically managed with Somatostatin analogues.
The hypothalamus produces Thyrotrophin Releasing Hormone (TRH). TRH stimulates thryotropic cells in the anterior pituitary to produce Thyroid Stimulating Hormone (TSH). TSH is released in low amplitude pulses, following a circadian rhythm (In this case, there are higher levels at night and lower levels in the morning).
TSH binds to receptors on follicular cells of the thyroid gland, stimulating the production of thyroid hormones: Tri-iodothyronine (T3) and Tetra-iodothyronine (T4), also known as Thyroxine. Control of this system is via negative feedback: high levels of T3 and T4 inhibit TRH and TSH production by the hypothalamus and anterior pituitary gland, respectively. This is depicted in the diagram below:
The actions of T3 and T4 are widespread. Some important functions include:
- Metabolic – increasing basal metabolic rate and promoting catabolism e.g. lipolysis, glycogenolysis, glycolysis and proteolysis
- Nervous system – important for speed of reflexes and mental activity
- Cardiovascular system – increases synthesis of cardiac muscle protein, increases cardiac output
- Bone – increases bone mineralisation
Further information on the thyroid gland can be found here.
The Hypothalamo pituitary gonadal axis is fundamental to the control of the reproductive system. Gonadotropin Releasing Hormone (GnRH) is released in a pulsatile fashion from the hypothalamus.
This stimulates gonadotroph cells of the anterior pituitary to produce two hormones equally:
- Luteinising Hormone (LH)
- Follicle Stimulating Hormone (FSH)
These then act on the gonads (testes/ovaries), and have different functions in males and females.
LH stimulates the testes to produce testosterone, the main male sex steroid hormone.
Testosterone has systemic effects to produce male secondary sex characteristics:
- Growth of pubic hair, axillary hair and facial hair
- Growth of external genitalia
- Deepening of voice
- Muscle growth
In addition, testosterone helps to maintain libido (sexual drive) and promotes anabolic reactions. Within the testes, testosterone acts to aid the formation of sperm (spermatogenesis). Testosterone has a negative feedback effect on the hypothalamus to inhibit GnRH production.
FSH drives sperm production at the testes (spermatogenesis), as well as stimulating the testes to produce the hormone inhibin. Inhibin has a selective negative feedback effect on FSH only and not LH (i.e. inhibits FSH production, but does not inhibit LH production).
LH stimulates the ovaries to produce androgens. FSH stimulates:
- Follicle growth
- Conversion of androgens to oestrogen
- Release of the hormone Inhibin from the ovaries.
Oestrogen at moderate concentrations has a negative feedback effect on LH and FSH secretion. Oestrogen alone (in the absence of progesterone) at high concentrations promotes LH and FSH secretion. Inhibin, like in the male, has a selective negative feedback effect on FSH only and not LH.
Progesterone is a sex steroid released by the corpus luteum, which is the remain of the follicle after ovulation. Progesterone increases the inhibitory effect of moderate oestrogen concentration. Progesterone prevents the positive feedback of a high oestrogen concentration. For more information about how this impacts contraception, click here.
Prolactin (PRL) is produced by the lactotroph cells of the anterior pituitary gland. Its pulsatile secretion follows a circadian rhythm with a nocturnal peak during sleep and a second (but lesser) peak in the evening. The main action of prolactin is to initiate and maintain lactation (milk production/secretion) of breast tissue. Prolactin is under inhibition by dopamine (DA), a neurotransmitter released from the hypothalamus.
(Note that the prolactin axis is the only axis where a hypothalamic hormone inhibits the release of the pituitary hormone instead of stimulating it).
Conversely, Thyrotropin Releasing Hormone (TRH), also from the hypothalamus, stimulates the release of prolactin but this is only a minor positive feedback effect. In addition, oestrogens also have a positive feedback effect on Prolactin, stimulating its release. Prolactin has a negative feedback effect on GnRH at the hypothalamus, inhibiting its release. Prolactin blocks the action of LH on the gonads (ovaries and testes).
Clinical Relevance – Hyperprolactinaemia
Hyperprolactinaemia is a state of raised prolactin levels, resulting in galactorrhoea (leakage of milk from breast tissue). The causes can be remembered as the 5 Ps:
- Physiological (Stress, Sleep, Sexual Intercourse)
- Pharmacological e.g. dopamine antagonists
- Prolactinoma (a pituitary tumour specifically of prolactin producing cells)
- Polycystic Ovarian Syndrome (PCOS)