The Anterior Pituitary

The Anterior Pituitary While the posterior pituitary is controlled by neuronal signals and there is no hormone synthesis, the anterior lobe receives releasing hormones, such as growth hormone releasing hormone from the arcuate and paraventricular nuclei via the blood, and the anterior pituitary will then synthesise its hormones. The anterior pituitary projects to many organs such as the breasts (prolactin), testis and ovary (FSH and LH), thyroid gland (TSH), adrenal gland (ACTH). There is interaction and control of hormone secretion at every level: the hypothalamus, the pituitary and the endocrine organs. For example, the anterior pituitary will receive releasing or inhibitory signals from the hypothalamus. If the hormones are stimulatory, for example TRH or CRH, the anterior pituitary will synthesise and secrete TSH and ACTH respectively. The T3 and T4 released from the thyroid gland in response to TSH will negatively inhibit the anterior pituitary from secreting more TSH. The case with the adrenal gland is similar: the glucocorticoids secreted by the adrenal in response to Acth NEGATIVELY feedbacks the anterior pituitary to stop producing ACTH. An interesting case is the feedback control of LH. LH stimulates the ovary to secrete estrogens. Negative r positive feedback loops depends on the time in the woman’s cycle. During ovulation, e2 will have a positive effect on the anterior pituitary allowing it to secrete more LH. However pre-ovulation, this loop is a negative feedback control. Control is also dine via a short loop, the pituitary hormone shuts down the hypothalamus, and reduces its secretion of releasing hormones. An ultra short loop also exists, where the hypothalamus hormone, e.g. TRH, shuts down its own production. A hormone secreted by the anterior pituitary is growth hormone. Growth Hormone releasing hormone, secreted from the paraventricular and arcuate nuclei of the hypothalamus. Another hormone secreted from the hypothalamus in a pulsitile fashion is GHrelin. This hormone is stimulatory to the anterior pituitary somatotrophes. It is not only the hypothalamus that secretes GHrelin, the stomach and SI also contributes. There is also somatostatin, which has an inhibitory action on the anterior pituitary, and is used pharmacologically in patients who have tumours to suppress their growth. Hence there should be a balance between GHRH and somatostatin. Of the three hormones controlling the anterior pituitary to secrete growth hormone somatostatin is the smallest; being only 14AA, while GHRH is 44AA and GHrelin is 28Aa. sOmatostatin, is also the only hormone when compared with the rest relating to GH release that has five receptors with 50% homology that recognise it, showing us how important tight controlling of GH secretion is. Growth hormone’s effect on the liver is the production of insulin like growth factor I, which feedbacks to the pituitary to shut of the production of growth hormone. Stress and exercise are both stimulatory to GH secretion. Sleep rhythms are also important since the highest amount of growth hormone is released between 12 and 4 am. Hyperglycaemia stunts the production of growth factor, as is seen in children who have Type I diabetes: these have short

statures. Other stimulatory effects include increase in amino acids. On the other hand, an increase in free fatty acids is inhibitory. Chronic illness such as leukaemia and its treatment by chemotherapy is also inhibitory to GH secretion. In addition to GH, another three hormones are required for growth all controlled by the anterior pituitary: estrogens/testosterone, cortisol and thyroxin. The metabolic effects of growth hormone are due not only to the direct effects of GH, but also through its indirect effects by IGF-1.Growth Hormone has a short half-life and for this reason, patients that are to be administered additional GH, are given GH at night, where the body secretes GH itself, so that it would be at a higher concentration at that time. Due to its short half life, its binding protein in the blood, serves as its reservoir. These binding proteins may have both low and high binding affinity to GH. These binding proteins resemble the GH receptors on cell membranes. There is a gender difference in pubertal growth. Girls start puberty at the age of 12, while boys start at the age of 15. This is important, as after this age growth hormone cannot be administered, as the effect of growth hormone is maximum before puberty. The effects of growth hormone are to break down fats and increase protein synthesis. As increased levels of growth hormone are taken e.g., in body builders, there is decreased insulin sensitivity and diabetes may result. GH also retains sodium, which will retain water which can also be dangerous in athletes taking growth hormone, as this can result in hypertension. IGF-1 has insulin like activity; however a high concentration of this hormone is required to have that effect. When GH binds to its receptor, this dimerises, and JAK 2 which has tyrosine kinase activity bind to the receptor once this dimerizes. This will phosphorylate STAT, which goes to the nucleus to modify gene expression. IGF-1 secreted by the various types of cells in response to GH, enters the circulation, bound to many types of OGFBPs, which themselves can have a metabolic activity. IGFBPs increase T1/2 and bring IGFs to required sites. In the circulation many proteases, break the protein binding protein and IGf apart. Bones have IGF as well as GH receptors. Both will stimulate epiphyseal growth. Some IGF-1 is also produced by the bones themselves (pARacrine). Testosterone and oestrogen also may stimulate its production. IGF II is not linked to GH control. Its metabolic effect is not through its own receptor but through receptor of insulin and IGFI. Prolactin is another hormone secreted from the anterior pituitary. Its regulation of secretion is an inhibitory one. Anything that disturbs this inhibition results in the secretion of the hormone. The prolactin release inhibitory protein is dopamine, while the prolactin releasing hormone is a very strong player in secretion. Regulators of prolactin secretion include sleep, stress, exercise, vaginal stimulation, pregnancy, due to increased

oestrogen (also oestrogen in pill may cause lactation), breast feeding by stimulation of the nipples, hypothyroidism, VIP. Long term medications suppress prolactin The PRH is secreted as a preprohormone. It is secreted by dorsomedial hypothalamic nucleus and the supraoptic nucleus. Its receptor has a 7TM domain and uses cAMP. Dopamine the inhibitory hormone which is also a neurotransmitter, acts on D2 receptors on lactotrophes and activates G inhibitory protein. Most tumours in the pituitary effect prolactin secreting calls (lactotrophes). A person with a prolactin secreting tumour should never be put n the contraceptive pill or advised to get pregnant, where the increased concentration of oestrogen may result in growth of the tumour, which may affect the supraoptic nucleus if it enlarges. Some women have increased prolactin, but this is not active, in this case there is no need to treat patient.