The pituitary gland is a tiny pea-sized organ at the base of the brain. Sometimes referred to as the "master gland", it produces and secretes many hormones that work all over the body, controlling a number of physiological processes that are paramount to our health. This thesis will concentrate on prolactin, with growth hormone a close second, but the pituitary gland also secretes thyroid-stimulating hormone, antidiuretic hormone, oxytocin, follicle-stimulating hormone as well as many others.
Prolactin is a pituitary peptide hormone that is mainly associated with lactation. It was discovered by Dr Henry Friesen and is between 194 and 199 amino acid residues, depending on the species. It is a single chain polypeptide with a weight of 24,000 Daltons. The molecule is folded and stabilised by three disulphide bonds. Closely related to growth hormone, prolactin's main site of secretion is the anterior pituitary, by the lactotrophs located there. It is difficult to find a tissue that doesn't have prolactin receptors so it synthesised and secreted by a variety of other cells throughout the body: mainly immune cells, the brain and the decidua of the pregnant uterus. However the main focus of this thesis is prolactin's influence on the immune response. Many studies suggest it can act on a range of different immune cells and that it could be important in maintaining a variety of physiological processes within the body.
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In the 1920's it was discovered that extracts of the pituitary gland, when injected into rabbits stimulated milk production.R Further research revealed that prolactin has 2 major roles in milk production:
Inducing luboalveolar growth of the mammary gland. Alveoli are the groups of cells in the mammary gland that secrete the milk. During pregnancy, high levels of oestrogen circulate through the body and this causes an increase in prolactin which in turn causes maturation of the mammary glands, preparing them for the forthcoming lactation.
Stimulating lactogenesis (milk production) after giving birth. When a child sucks on its mothers nipple this stimulates the production of prolactin, which along with insulin and cortisol causes transcription of the genes that encode for milk proteins.
As well as being influenced by the sucking stimulus and oestrogen levels, prolactin secretion is positively regulated by thyroid-releasing hormone and gonadotropin-releasing hormone. Its release is inhibited by dopamine, which binds to lactotroph receptors and prevents both synthesis and secretion.
Prolactin has a broad range of other effects, including a role in several non-lactational aspects of reproduction. It is important in maintaining the murine corpus luteum (structure within the ovary that secretes progesterone), and mice that have an inactivated prolactin gene are infertile due to defects in ovulation, fertilisation, development and implantation.R
The prolactin receptor is widely expressed by immune cells, and some lymphocytes even synthesise and secrete prolactin.R This suggests that prolactin acts as an autocrine or paracrine modulator of immune activity but interestingly, mice with deleted prolactin genes do not show unusual changes in immune response. This suggests that prolactin appears to have a modulatory role in several aspects of immune function, but it is not necessarily required for a response.R
Growth hormone is similar in structure to prolactin and together they are part of a family of hormones probably descending from the same ancestral gene.R It is made up of around 190 amino acids and is secreted via somatotrophs in the anterior pituitary. It is involved in the growth of bone, cartilage and soft tissues as well as metabolism and like prolactin, it has shown some contribution to immune responses. It has 2 types of effects:
Direct effects on target cell receptors.
Indirect effects, through an insulin-like growth factor secreted from the liver in response to growth hormone release.
Growth hormone is used by athletes to enhance performance, and it can be seen as a drug of abuse by those using it in an extreme sense. It is also used for stimulating milk production in cattle, causing much controversy amongst farmers.R
The rate of GH secretion from the anterior pituitary is highest around puberty, and declines progressively from the age of thirty. Normal ageing causes a variety of effects such as a decrease in lean mass, an increase in fat mass and a decrease in bone density. These symptoms have been attributed to declining growth hormone levels. The clinical term for this is called the somatopause and symptoms include: frailty, muscle atrophy, weight gain, increase in bone fracture and loss of sleep pattern. On the other hand, some trials have shown that normal growth hormone levels may speed up the ageing process.R Mice with genetic dwarfism caused by a deficiency in growth hormone and also prolactin, in some instances have out-lived normal mice.
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Receptors for growth-hormone releasing hormone have been found on a number of immune cells, and the hormone itself has been found to enhance a number of immune responses. It can be produced by T-cells, B-cells and macrophages and after release it has been shown to enhance synthesis of some thymic hormones.R Bazinger-Tobler et al (2008) have shown that in rats with thymic atrophy and hence impairment of immune functions, treatment with growth hormone or prolactin restores the ability to produce an immune response.
In 1990, in an experiment done by a scientist named Rudman on a group of 61-81 year olds, it was shown that growth hormone treatment increased lean mass and bone density, decreased fat mass and also restored the thickness of the skin to that of a normal 50 year old.R After further trials it was shown that growth hormone consistently produced these results demonstrating it can counteract the catabolic effects of ageing. The question was, could it treat susceptibility to infection in the elderly?
Some studies would suggest that no, it could not. For example, when growth hormone therapy was carried out on the critically ill, it was expected to reduce the effects of the illness and decrease the patient's time in hospital. However, results showed not only a higher mortality rate accompanied with higher doses of growth hormone, but patients that survived spent longer in intensive care than the patients in the placebo group.R