The Hypothalamus And The Posterior Pituitary

The Hypothalamus and the Posterior Pituitary The classic endocrine glands are defined historically; however any group of cells that can secrete cytokines, which travels via the blood and affects any other cell, can also be classified as endocrine cells. These non-classical endocrine glands include: the brain, heart (ANP), kidney (erythropoietin), liver (insulin growth factor), adipose tissue (heptin- for satiety and control of body weight) and the GI tract (CCK) among various other cells. The principle endocrine gland in the brain is the hypothalamus, which is made up of nuclei and located just above the pituitary. It regulates through different nuclei: thirst, hunger, sexual behaviour (appetitive mechanisms), fear and rage (defence mechanisms), temperature regulation and neuroendocrine control on the anterior and posterior pituitary including also the biorhythms. A person with a hypothalamic tumour will among other deficits, experience continual hunger. The hypothalamus secretes various bioactive peptides, some of which will pass via the primary plexus into the portal hypophyseal vessel and into the anterior pituitary, while others end up in the posterior pituitary via neurons which secrete the peptides. The only two hormones secreted from the posterior pituitary are arginine vasopressin and oxytocin. Arginine vasopressin is a peptide, 9 amino acids long with a disulfide bridge influencing the peptide fold. The pathology involving this hormone displays the vital role this amino acid plays. People who have diabetes insipidus, whose receptors do not recognise ADH, pass urine all the time. Oxytocin is also 9amino acids long, and differs only slightly structurally from arginine vasopressin. There is only a 2 amino acid difference, and oxytocin also has a disulfide bond characterizing its shape. However, unlike arginine vasopressin, this hormone is not vital 2 existences, however is important in woman especially during labour. Both enzymes being hydrophilic are secreted as prohormones, much larger in size than the final peptide hormone. Glycophysin II and I on AVP and oxytocin respectively, together with the glycopeptides at the end of the prohormone, in the past were seen to be background sequences, however new ideas are emerging that these “extra” peptides might actually have a role. These “extra” peptides together with the signal peptide upstream the hormone sequence are spliced to form the active hormone. AVP functions in dehydration and in cases of blood loss. When the body is deprived of water, through excessive sweating for example, the plasma osmolality increases. The osmoreceptors situated around the major arteries, for example the carotids sense this increased osmolality and release AcH. When there is a decrease in central blood volume, e.g. by a road traffic accident rupturing the spleen or liver. This causes a decreased blood pressure, resulting in cranial nerves 9 and 10 to release their constant tonic inhibitory impulses. This

will result in a decreased alpha adrenergic inhibition and the release of AVP from neurons. Other factors regulate AVP, including pain or stress. In this case AVP will prepare the brain and muscles with the perfusion required for flight and fight reactions. In fever, sweating increases, so does the release of AVP, to help the kidney CD and thick cortical tubule to become more permeable to water. In fact that is the reason why urine is more concentrated when a patient is feverish. B adrenergic agents also increase the concentration of avp by helping to reduce the tonic inhibition of alpha adrenergic receptors. Estrogens also stimulates AVP, in fact when oestrogen levels are high, women feel bloated. Stimulatory to AVP are also opiates, nicotine and prostaglandins. AVP is inhibited by alpha adrenergic agents. Atrial Naturetic Peptide also inhibits AVP. ANP allows the kidney to excrete a higher concentration of salt and water in urine. Ethanol is also another AVP depressor such is hypothermia. If there is a decreased water intake, or a decreased appetite for salt, the blood pressure will decrease and the plasma volume will also decrease. This will inhibit venous return, which will inhibit the secretion of ANP, since a high venous return is required for this enzyme to be secreted. ANP usually will act on the kidney directly by increasing the secretion of sodium and water in urine and decreasing the concentration of rennin, which will decrease plasma volume. The kidney is also affected indirectly by ANP which decrease aldosterone release. Thus if a low venous return inhibits ANP, the processes just described will be reversed. The secondary actions of AVP are hypothermia- why this hormone is shut down during hypothermia, and why it is switched on in fevers. AVP also facilitates memory and consolidation and peripheral vasoconstriction. AVP acts on three receptors: V1a, V1b and V2, all of which are G proteins. V1b activation will result in an increased calcium concentration in cells which results in an increased vasoconstriction. Stimulation of the V1B, will also increase cellular calcium concentrations, ACTH is secreted which is a stimulus to the pituitary. The V2 receptor, when stimulated will result in an increase in cAMP as a second messenger. This will make the CD and thick ascending limb more water permeable. The pathology in nephrogenic diabetes insipidus is this receptor. Both men and woman have oxytocin production. The stimuli for secretion are vaginal and breast stimulation and the baby’s cry at birth. The cerebral cortex will recognise the cry and the paraventricular and supraoptic nuclei are stimulated to release oxytocin and there is the milk ejaculation reflex. In mothers who do not produce oxytocin, breast feeding may be difficult. Oxytocin is also helpful during labour. During pregnancy there is an increase in the oxytocin receptors. As the uterus grows it will contract at first irregularly but later on contraction is more frequent. When the baby’s head presses on the cervix, the cervix and vagina will dilate and nerves are sent to the posterior

pituitary, to secrete more oxytocin, which causes the uterine muscles to contract more. This is an example of a positive feedback mechanism. Secondary effects includes, curbing appetite for salt, uterine contractions during intercourse, contraction if vas deferens during ejaculation. Fever, high temperatures, pain and loud noise prevent oxytocin release.