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Mechanism of hormone actionTwo principal types of hormone receptor interactions are recognized I- In one type, lipid soluble substances, including steroidhormones, 1, 25- dihydroxy cholecalciferol, and thyroid hormones, pass freely through the plasma membrane and bind to a cytoplasmic receptor. The hormone receptor complex translocates to the chromatin of the cell nucleus to initiate the DNA- directed synthesis of mRNA.
II- The second type of hormone- receptor interaction involves water soluble substances, which can not permeate through the cell plasma membrane. Their first contact with the cell is to bind to protein receptors on the outer membrane surface. In order for the message to reach intracellular sites, the hormone receptor complex can be internalized (endosytosis) or the information could be transferred at the membrane site (transduction) and carried by other mediators or messengers within the cell compartments. Cellular activity is enhanced by removing the membrane restraint by increasing its permeability to the flow of ions or organic substances. Hormone binding to the cell membrane or by indirectly affecting sub cellular membrane is in effect removing a restraint to cell activity or subparticle interaction.
Water soluble hormones, neurotransmitters, or other agents (lectins and growth factors) bind to a cell surface receptor as a result of a non-covalent association with a relatively high affinity to initiate a set of membrane events. As a result there is a release of mediators (secondary messengers) that react with cytoplamic components. Most polypeptide hormones stimulate the production of cAMP as the secondary messenger. There are important exceptions to this i.e. Insulin and prolactin activity can be expressed without direct stimulation of adenylate cyclase.
Cyclic Nucleotides as second messengers Activation of adenylate cyclase as major route of hormone stimulation can be demonstrated by the addition of cAMP or dibutyryl cAMP to a target cell. The addition of the nucleotide mimics most of the actions of some hormones on cellular events. This is consistent with the effect of methylxanthines, such as caffeine, as inhibitors of phosphodiesterase, the enzyme that converts cAMP tot eh inactive 5'-AMP. The number of receptors on the cell membrane is relatively low (5000 10000 per cell). In most systems relatively few receptors, 10-20% of the total present, need to be occupied to produce a maximum response of the cell.
Pineal organ of teleosts The pineal organ is a part of the central nervous system and is formed, like the retina, as an evagination from the embryonic primary forebrain (dorsal roof of the diencephalon). During vertebrate evolution the pineal organ has transformed from a photosensory organ into an endocrine gland. In most poikilothermic vertebrates, the pineal complex has two components. In fish, they are the pineal and parapineal organs. The parapineal organ remains more or less rudimentary, close to the habenular nuclei of the diencephalon while the pineal organ grows to form a relatively large vesicle located dorsal to the forebrain, immediately below or within the skull roof.
The pineal organ is often differentiated into a proximal slender pineal stalk and a distal expanded end vesicle. In some species, the adult pineal organ is very large and covers the entire telencephalon. The wall of the pineal organ i.e. the pineal epithelium, is in principle a unistratified epithelium, which may be strongly folded in many species and may almost obliterate the central lumen of the pineal organ.
The pineal epithelium of teleost fish consists of photoreceptor cells, neurons and ependymal interstitial cells which are often called supportive cells, interstitial cells or glial cells. In addition, oligodendrocytes form myelin sheaths surrounding some neural axons while macrophages are found mainly in the central lumen. The photoreceptor cells are the source of the melatonin produced by the pineal organ. The lumen of the pineal organ remains as an extension of the 3rd ventricle of the brain in adult teleosts. The cerebropinal fluid (CSF) of the ventricular system is thus potentially a means of transport for various chemical compounds between the pineal organ and the brain.
The pineal organ is well vascularized. The blood vessels do not penetrate into parenchyma but remain outside the basal lamina in the perivascular space. The pineal organ generally lacks a blood-brain barrier, as reflected by the presence of fenestrated capillaries. The photoreceptor cells and the ependymal cells are tightly coupled by special intercellular junctions, forming a barrier for intercellular diffusion between the CSF of the pineal lumen and the perivascular space. Thus the pineal parenchyma is exposed to an extracellular environment reflecting haemal composition basally, and CSFcomposition apically i.e. towards the pineal lumen.
Photoreceptor cells Pineal photoreceptor cells may be distinguished into apical (receptor) and the basal (effector) poles. The apical pole contains the outer segment, which contains the light sensitive photopigment, and the inner segment which contains numerous mitochondria and (sometimes visible) longitudinal cytoskletal elements. The outer segment develops from 92+0 stereocilium, forming a stack of membrane lamellae that contain the photopigment. The basal pole is the photoreceptor axon, which forms contacts with postsynaptic neurons or with the basal lamina that surrounds the pineal parenchyma.
The apical pole may vary in shape and size. The outer segment lamellae may form a regular cone shaped stack, similar to that of retinal cone photoreceptors, but more often they form a dome-or cup-shaped stack. Often, the outer segments are irregular in shape and may consist of a mixture of lamellar and tubular membrane formations. The inner segment is typically a short, rounded structure, packed with mitochondria. It is elongated in some photoreceptor cells when it is usually attached to a short cone-shaped outer segment. The basal pole is also variable.
The large majority of the photoreceptor cells that are clearly pre-synaptic to intrapineal neurous possess short axons. However, a small number of photoreceptor cells possess long axons that have been shown to project directly to the brain. There are numerous photoreceptor cells that are not clearly presynaptic to neurons but possess basal processes that terminate without synaptic specializations on the basal lamina. Photoreceptor axon terminals impinging mainly on the dendrites but also on cell bodies and axons of intrapineal neurons, typically contain so-called synaptic ribbons. This type of photoreceptor-to-neuron contact has been observed in most teleosts.
Interstitial cells The large portion of the cells of the pineal parenchyma consists of so-called supportive or interstitial cells. They are located between the photoreceptor cells to which they are attached by tight junctions which thus form a diffusion barrier between CSF of the pineal lumen and the extra-cellular fluid surrounding the photoreceptor cell bodies and axons, and the intrapineal neurons. In most species they appear to have widely extending basal poles that line the basal lamina forming a sheet that separates neural elements and the basal pedicles of most photoreceptor cells, from the perivascular space. In view of their location (i.e. lining the ventricle) and their cytoskeletal constituents, this cell type fulfils criteria for both ependymal and glial elements.
NEURONS The pineal organ of some teleost species contains an impressive neuronal population. It appears that the vast majority of intrapineal neurons send axonal projections to the brain i.e. they are analogous to the ganglion cells of the retina. Intrapineal neurons are postsynaptic to photoreceptor cells. The neurons also form conventional synapses between each- other as well as with photoreceptor cells. Axo-axonal synapses have been observed in the pineal tract. The vast majority of the axons in the pineal tract (axonal projections from intrapineal neuronal population and some photoreceptor cells) are unmyelinated, but oligodendrocytes form myelin sheaths around a small traction of the axons that project to the brain and a small number of myelinated axons have been found in fishes.
Macrophages Macrophages have been noted to be present in the pineal lumen in several species, often in close contact with photoreceptor outer segments. They are believed to be involved in the degradation of degenerating photoreceptor cells and / or photoreceptor outer segments. Also macrophages have been observed in the pineal epithelium and perivascular space where they are believed to take up and digest substances penetrating from the bloodstream.
Melatonin Synthesis (Photoperiod vs endogenous rhythm) The synthesis of melatonin by the pineal organ is regulated by the intensity of the ambient illumination and reaches the highest level in complete darkness i.e. under natural conditions, during the night. Melatonin synthesis by the pineal organ is regulated by the ambient light-dark cycle, being high during the dark period (scotophase) and low during the light period (photophase). Pineal serotonin content also shows a diurnal rhythm, with the highest level during scotophase in the pike, during dark-light transition in the eel and with higher levels in continuous darkness in continuous light.
The melatonin synthesis profile of the pineal organ is reflected in the plasma levels of melatonin : melatonin levels are highest at night and low during day. Removal of pineal organ may or may not eliminate the nocturnal rise in plasma melatonin. While melatonin synthesis by the mammalians gland is indirectly controlled by the environmental photoperiod via the cir cadian oscillator