The Pineal Gland PDF

The pineal gland Also called the pineal body or the “third eye") is a small endocrine gland in the vertebrate brain. It is a small, reddish gray, its shape resembles a tiny pine cone (hence its name), and it is located near the center of the brain. The pineal varies in size among species; in humans...

The pineal gland Also called the pineal body or the “third eye") is a small endocrine gland in the vertebrate brain. It is a small, reddish gray, its shape resembles a tiny pine cone (hence its name), and it is located near the center of the brain. The pineal varies in size among species; in humans it is roughly 1 cm in length, whereas in dogs it is only about 1 mm long. Historically, its location deep in the brain suggested to philosophers that it possessed particular importance. This combination led to its being a "mystery" gland with myth, superstition and occult theories surrounding its perceived function. Rene Descartes, called it the "seat of the soul". He believed that it was the point of connection between the intellect and the body.  The main function of the pineal gland : The pineal gland is a flat, cone-shaped organ about the size of a pea lying in the center of the midbrain. It reaches its largest mass during childhood, but calcifies and shrinks with age. It produces the serotonin derivative melatonin, a hormone that affects the modulation of wake/sleep patterns and seasonal functions. Melatonin production by the pineal gland is determined by the amount of light received, for the gland plays the role of a bodily clock, due to its sensitivity to light and regulation of the sleep- wake cycle. During nighttime sleep, melatonin levels in the body rise, reaching a peak between 11 PM and 2 AM, and then drop dramatically when a new day dawns. Melatonin production is related to age, increasing at three months after birth, peaking at the age of six, and beginning to drop after puberty.  Other functions: Melatonin is related to the mechanism by which some amphibians and reptiles change the color of their skin and, indeed, it was in this connection the substance first was discovered. Scientists reported that extract of the pineal glands of cows lightened frog skin (1917). Dermatology professors used it in the hope that a substance from the pineal might be useful in treating skin diseases, isolated and named the hormone melatonin in 1958. In the mid-70s they demonstrated that the production of melatonin exhibits a circadian rhythm in human pineal glands. The discovery that melatonin is an antioxidant was made in 1993.  How does the retina transmit information about light-dark exposure to the pineal gland? Light exposure to the retina of the eye is first relayed to the suprachiasmatic nucleus of the hypothalamus, an area of the brain well known to coordinate biological clock signals. Fibers from the hypothalamus descend to the spinal cord and ultimately project to the superior cervical ganglia, from which post-ganglionic neurons ascend back to the pineal gland. Production of melatonin by the pineal gland is inhibited by light and permitted by darkness. For this reason melatonin has been called "the hormone of darkness". Synthesis and secretion of melatonin is dramatically affected by light exposure to the eyes. The fundamental pattern observed is that serum concentrations of melatonin are low during the daylight hours, and increase to a peak during the dark. The precursor to melatonin is serotonin, a neurotransmitter that itself is derived from the amino acid tryptophan.  The duration of melatonin secretion each day is directly proportional to the length of the night The mechanism behind this pattern of secretion during the dark cycle is that activity of the rate-limiting enzyme in melatonin synthesis - serotonin N- acetyltransferase (NAT) - is low during daylight and peaks during the dark phase. In some species, circadian changes in NAT activity are tightly correlated with transcription of the NAT messenger RNA, while in other species; post-transcriptional regulation of NAT activity is responsible. Activity of the other enzyme involved in synthesis of melatonin from serotonin- Hydroxyindole-O-methyltransferase (HIOMT)- does not show regulation by pattern of light exposure. Two melatonin receptors have been identified from mammals (designated Mel1A and Mel1B) that are differentially expressed in different tissues and probably participate in implementing differing biologic effects. These are G protein- coupled cell surface receptors. The highest density of receptors has been found in the suprachiasmatic nucleus of the hypothalamus, the anterior pituitary (predominantly pars tuberalis) and the retina. Receptors are also found in several other areas of the brain.  Biological Effects of Melatonin 1- Circadian rhythm or sleep-awake cycles (Biological clock): Melatonin is probably not a major regulator of normal sleep patterns, but undoubtedly has some effect. There is some indication that melatonin levels are lower in elderly insomniacs relative to age matched non- insomniacs, and melatonin therapy in such cases appears modestly beneficial in correcting the problem. 2- Powerful antioxidant activity: Melatonin is an antioxidant that can easily cross cell membranes and the blood-brain barrier. Melatonin is a direct scavenger of OH, O2−, and NO. Unlike other antioxidants, melatonin does not undergo redox cycling, the ability of a molecule to undergo reduction and oxidation repeatedly. Redox cycling may allow other antioxidants (such as vitamin C) to act as pro- oxidants, counterintuitively promoting free radical formation. Melatonin, on the other hand, once oxidized, cannot be reduced to its former state because it forms several stable end-products upon reacting with free radicals. Therefore, it has been referred to as a terminal (or suicidal) antioxidant. 3- Melatonin has been demonstrated to prevent the damage to DNA by some carcinogens, stopping the mechanism by which they cause cancer. It also has been found to be effective in protecting against brain injury caused by reactive oxygen species (ROS). Melatonin also enhances immunity and decrease the deposition of β-amyloid protein (the main responsible protein of Alzheimer's disease) in the brain cells. 4- Effects of Melatonin on Reproductive Function: Seasonal changes in daylength have profound effects on reproduction in many species, and melatonin is a key player in controlling such events. In temperate climates, animals like hamsters, horses and sheep have distinct breeding season. During the non-breeding season, the gonads become inactive (e.g males fail to produce sperm in any number), but as the breeding season approaches, the gonads must be rejuvenated. Photoperiod - the length of day vs night - is the most important cue allowing animals to determine which season it is. The pineal gland is able to measure daylength and adjust secretion of melatonin accordingly. A hamster without a pineal gland or with a lesion that prevents the pineal from receiving photoinformation is not able to prepare for the breeding season. The effect of melatonin on reproductive systems can be summarized by saying that it is anti-gonadotropic. In other words, melatonin inhibits the secretion of the gonadotropic hormones luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the anterior pituitary. Much of this inhibitory effect seems due to inhibition of gonadotropin-releasing hormone from the hypothalamus, which is necessary for secretion of the anterior pituitary hormones. One practical application of melatonin's role in controlling seasonal reproduction is found in its use to artificially manipulate cycles in seasonal breeders. For example, sheep that normally breed only once per year can be induced to have two breeding seasons by controlling melatonin concentrations.  Antidiuretic hormone (Vasopressin) It also called Arginine vasopressin (AVP) argipressin or antidiuretic hormone (ADH). It found in most mammals. Vasopressin is a 9 amino acids that controls the reabsorption of molecules in the tubules of the kidney by affecting the tissue's permeability. It also play important roles in increasing blood pressure. It plays a key role in homeostasis, and the regulation of water, glucose, and salts in the blood. It is synthesized in the hypothalamus and stored in vesicles at the posterior pituitary. to be released into the bloodstream; however, some AVP is also released directly into the brain.  The main Biological function of ADH: One of the most important roles of AVP is to regulate the body's retention of water; it is released when the body is dehydrated and causes the kidneys to conserve water, thus concentrating the urine, and reducing urine volume. In high concentrations, it also raises blood pressure by inducing moderate vasoconstriction.  Control of Antidiuretic Hormone Secretion The most important variable regulating antidiuretic hormone secretion is plasma osmolarity, or the concentration of solutes in blood. Osmolarity is sensed in the hypothalamus by neurons known as an osmoreceptors, and those neurons, in turn, stimulate secretion from the neurons that produce antidiuretic hormone. When plasma osmolarity is below a certain threshold, the osmoreceptors are not activated and antidiuretic hormone secretion is suppressed. When osmolarity increases above the threshold, the ever-alert osmoreceptors recognize this cue to stimulate the neurons that secrete antidiuretic hormone. Antidiuretic hormone concentrations rise steeply and linearly with increasing plasma osmolarity. Osmotic control of antidiuretic hormone secretion makes perfect sense. Imagine walking across a desert: the sun is beating down and you begin to lose a considerable amount of body water through sweating. Loss of water results in concentration of blood solutes - plasma osmolarity increases. Should you increase urine production in such a situation? Clearly not. Rather, antidiuretic hormone is secreted, allowing almost all the water that would be lost in urine to be reabsorbed and conserved. There is an interesting parallel between ADH and thirst. Both phenomena appear to be stimulated by hypothalamic osmoreceptors. Howerver, The osmotic threshold for ADH secretion is considerably lower than for thirst, as if the hypothalamus is saying "Let's not bother him by invoking thirst unless the situation is bad enough that antidiuretic hormone cannot handle it alone."  Secretion of antidiuretic hormone is also stimulated by decreases in blood pressure and volume. Changes in blood pressure and volume are not nearly as sensitive a stimulator as increased osmolarity, but are nonetheless potent in severe conditions. For example, Loss of 15 or 20% of blood volume by hemorrhage results in massive secretion of antidiuretic hormone. Another potent stimulus of antidiuretic hormone is nausea and vomiting, both of which are controlled by regions in the brain with links to the hypothalamus.  Water transport inside body Diffusion Aquaporines Through Proteinic channels inserted into the of permeable plasma plasma membrane bilayer. They are membranes tetramers containing 4 permeable channels to water molecules, in both depending on the directions. There are many types differences in of aquaporins called aquaporins-0 osmolality on both (AQP-0), aquaporin-1 (AQP-1)… up to sides of lipid aquaporin-10 (AQP-10). AQP-1 are bilayers of the present especially in red cells, kidneys, plasma choroid plexus; AQP-2, in the kidney membranes. This (collecting tube) and are controlled by transfer is slow and vasopressin, AQP- 4 in the brain, AQP-7 of low importance. and AQP- 9 in adipocytes.  Mechanism of action of ADH on the kidney It acts through V2 receptors (G-coupled protein receptor) on the plasma membrane which activates adenylyl cyclase III and VI to convert ATP into cAMP. The rise in cAMP then increases the number of aquaporin-2 water channels biosynthesis. cAMP activates protein kinase A (PKA) to add phosphate groups to proteins (including the aquaporin-2 protein) to allow water to move out of the nephron, increasing the amount of water re-absorbed from the forming urine back into the bloodstream.  Vasopressin secretion disorders Nephrogenic diabetes Hypothalamic ("central") insipidus diabetes insipidus the kidney is unable to results from a deficiency in respond to ADH. Most secretion of antidiuretic commonly, this results from hormone from the posterior some type of renal disease, pituitary. Causes of this but mutations in the ADH disease include head trauma, receptor gene or in the gene and infections or tumors encoding aquaporin-2 have involving the hypothalamus. also been demonstrated in affected humans. The major sign of either type of diabetes insipidus is excessive urine production (polyuria). It can be treated with exogenous antidiuretic hormone.