Dr. Allerton recognized that in order for the brain to function properly and for the neurotransmitters in the brain to receive messages, the hypothalamus must be working correctly, since it is the functioning center for four of the brains most powerful hormones (neurotransmitters) that affect the mind; Serotonin, Dopamine, Norepinephrine and acetylcholine. It was his feeling that improper Hypothalamic function could be the cause of most of the mental problems/chemical imbalances that affect children and adults.
The general functions of the hypothalamus are of extreme importance to the body, such as:
- Pituitary gland regulation
- Blood pressure regulation
- Hunger and salt cravings
- Feeding reflexes
- Body temperature regulation
- Heart rate
- Bladder function
- Water preservation
- Hormonal/neurotransmitter regulation
- Ovarian function
- Testicular function
- Mood & behavioral functions
- Sleep cycles
- Energy levels
The main function of the hypothalamus is homeostasis, or maintaining the body’s status quo. Factors such as blood pressure, body temperature, fluid and electrolyte balance, and body weight are held to a precise value called the set-point. Although this set-point can migrate over time, from day to day it is remarkably fixed.
What is the Hypothalamus?
The Hypothalamus is the control center of all autonomic regulatory activities of the body. It has been said that the hypothalamus is the brain of the brain. It is the hub for automatic and endocrine homeostatic systems such as cardiovascular, temperature, and abdominal visceral regulation. It manages all endocrine hormonal levels, sensory processing, and organizing body metabolism, as well as ingestive behaviors. It appears that almost everything the Hypothalamus does is related in some way to the management of brain and body connection, linking the psyche (mind) to the body.
The hypothalamus is an integral part of the substance of the brain. A small cone-shaped structure, it projects downward, ending in the pituitary (infundibular) stalk, a tubular connection to the pituitary gland. The round bony cavity containing the pituitary gland is called the sella turcica. The posterior portion of the hypothalamus, called the median eminence, contains many neurosecretory cells. Important adjacent structures include the mammillary bodies, the third ventricle, and the optic chiasm, the last being of particular concern to physicians because pressure from expanding tumours or inflammations in the hypothalamus or pituitary gland may result in severe visual defects or total blindness. Above the hypothalamus is the thalamus. (For discussion of the function of these surrounding structures, see the nervous system.)
Regulation of hormone secretion
The hypothalamus regulates homeostasis. It has regulatory areas for thirst, hunger, body temperature, water balance, and blood pressure, and links the nervous system to the endocrine system.
The hypothalamus, like the rest of the brain, consists of interconnecting nerve cells ( neurons) with a rich blood supply. To understand hypothalamic function it is necessary to define the various forms of neurosecretion. First, there is neurotransmission, which occurs throughout the brain and is the process by which one nerve cell communicates with another at an intimate intermingling of projections from the two cells (a synapse). This transmission of an electrical impulse from one cell to another requires the secretion of a chemical substance from a long projection from one nerve cell body (the axon) into the synaptic space. The chemical substance that is secreted is called a neurotransmitter. The process of synthesis and secretion of neurotransmitters is similar to that shown in Figure 1 with the exception that neurosecretory granules migrate through lengths of the axon before being discharged into the synaptic space.
Neurologists have long been aware of four classical neurotransmitters: epinephrine, norepinephrine, serotonin, and acetylcholine, but recently there have emerged a large number of additional neurotransmitters, of which an important group is the neuropeptides. While bioamines and neuropeptides function as neurotransmitters, some of them also perform the role of neuromodulators; they do not act directly as neurotransmitters but rather as inhibitors or stimulators of neurotransmission. Well-known examples are the opioids (for example, enkephalins), so named because they are the naturally occurring peptides with a strong affinity to the receptors that bind opiate drugs such as morphine and heroin. In effect, they are the body’s opiates.
Thus the brain, and indeed the entire central nervous system, consists of an extraordinary network of neurons interconnected by neurotransmitters. The secretion of specific neurotransmitters, modified by neuromodulators, lends an organized, directed function to the overall system. These neural connections extend upward from the hypothalamus into other key areas, including the cerebral cortex. The result is that intellectual and functional activities as well as external influences, including stresses, can be funneled into the hypothalamus and thence to the endocrine system, from which they may exert effects on the body.
In addition to secreting neurotransmitters and neuromodulators, the hypothalamus synthesizes and secretes a number of neurohormones. The neurons secreting neurohormones are true endocrine (neurohemal) cells in the classical sense since secretory granules containing neurohormones travel from the cell body through the axon to be extruded, where they enter directly a capillary network, thence to be transported through the hypophyseal-portal circulation to the anterior pituitary gland.
Finally, the neurohypophysis, or posterior lobe of the pituitary gland, provides the classical example of neurohormonal activity. The secretory products, mainly vasopressin and oxytocin, are extruded into a capillary network, which feeds directly into the general circulation.
The existence of hormones of the hypothalamus was predicted well before they were detected and chemically characterized, and they have been studied intensively by many investigators. Two groups of American investigators, led by Andrew Schally and Roger Guillemin, respectively, shared the Nobel Prize for Physiology or Medicine for 1977 for their research on pituitary hormones.
These neurohormones are known as releasing hormones because the major function generally is to stimulate the secretion of hormones originating in the anterior pituitary gland. They consist of simple peptides (chains of amino acids) ranging in size from only three amino acids (thyrotropin-releasing hormone) to 44 amino acids (growth hormone-releasing hormone).
- Thyrotropin-releasing hormone (TRH), a neurohormone, is the simplest of the hypothalamic neuropeptides. It consists essentially of three amino acids in the sequence glutamic acid–histidine–proline. The simplicity of this structure is deceiving for TRH is involved in an extraordinary array of functions. Not only is it a neurohormone that stimulates the secretion of thyroid-stimulating hormone from the pituitary, and, quite independently, the secretion of another pituitary hormone called prolactin, but it also subserves other central nervous system activities because it is a widespread neurotransmitter or neuromodulator within the brain and spinal cord. There is evidence that TRH is involved in the control of body temperature and that it has psychological and behavioral effects, at least in animals. It may also have therapeutic value. There are studies suggesting that it mitigates the damage induced by spinal cord injury and that it leads to some improvement in the nervous disease known as amyotrophic lateral sclerosis (Lou Gehrig’s disease).These multiple effects are less surprising when it is considered that TRH appeared very early in the evolutionary scale of vertebrates and that, while the concentration of TRH is greatest in the hypothalamus, the total amount of TRH in the remainder of the brain far exceeds that of the hypothalamus. The TRH-secreting cells are subject to stimulatory and inhibitory influences from higher centres in the brain and they also are inhibited by circulating thyroid hormone. In this way TRH forms the topmost segment of the hypothalamic-pituitary-thyroid axis.
- Gonadotropin-releasing hormone (GnRH), a neurohormone also known as luteinizing hormone-releasing hormone (LHRH), is a peptide chain of 10 amino acids. It stimulates the synthesis and release of the two pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). While some investigators hold that there are two types of GnRH, most evidence supports the conclusion that only one type of neuropeptide stimulates the release of the two gonadotropins and that the variations in levels of both gonadotropins in the circulation are due to other modulating factors.Characteristic of all releasing hormones and most striking in the case of GnRH is the phenomenon of pulsatile secretion. In normal individuals, GnRH is released in spurts at intervals of about 80 minutes. The pulsatile administration of GnRH in large doses results in an ever-increasing concentration of gonadotropins in the blood. In striking contrast, the constant infusion of GnRH suppresses gonadotropin secretion. This phenomenon is advantageous for persons for whom suppression is important. Such persons include children with precocious puberty, and elderly men with cancer of the prostate. On the other hand, pulsatile administration of GnRH is efficacious in men or women in whom deficiency of gonadal function is due to impaired secretion of GnRH. A potential application of this phenomenon is the synthetic modifications of GnRH as a male as well as a female contraceptive.
Neurons that secrete GnRH have connections to an area of the brain known as the limbic system, which is heavily involved in the control of emotions and sexual activity. Studies in rats deprived of pituitary glands and ovaries but maintained on physiological amounts of female hormone (estrogen) have demonstrated that the injection of GnRH results in complex and striking changes in posture characteristic of the receptive female stance for sexual intercourse.
Some individuals have hypogonadism (in which the functional activity of the gonads is decreased and sexual development is inhibited) due to a congenital deficiency of GnRH, which responds to treatment with GnRH. Most of these people also suffer from hypothalamic disease and are deficient in other releasing hormones as well, but there are also individuals in whom GnRH deficiency is isolated and associated with a loss of the sense of smell (anosmia). Abnormalities in the pulses of GnRH secretion result in subnormal fertility, abnormal or absent menstruation, and possibly cystic disease of the ovary or even ovarian cancer.
- Corticotropin-releasing hormone (CRH), a neurohormone, is a large peptide consisting of a single chain of 41 amino acids. It stimulates not only secretion of corticotropin in the pituitary gland but also the synthesis of corticotropin in the corticotropin-producing cells (corticotrophs) of the anterior lobe of the pituitary gland. Many factors, both neurogenic and hormonal, regulate the secretion of CRH, since CRH is the final common element directing the body’s response to all forms of stress, whether physical or emotional, external or internal. (This key role of CRH in the hypothalamic-pituitary-adrenal axis is discussed below in connection with the adrenal gland.) Among the hormones that play an important role in modulating the influence of CRH is cortisol, the major hormone secreted by the adrenal cortex, which, as part of the negative feedback servomechanism (exerting control over another system through negative feedback), blocks the secretion of CRH. Vasopressin, the major regulator of the body’s excretion of water, has an additional ancillary role in stimulating the secretion of CRH.Excessive secretion of CRH leads to an increase in the size and number of corticotrophs in the pituitary gland, often resulting in a pituitary tumour. This, in turn, leads to excessive stimulation of the adrenal cortex, resulting in high circulating levels of adrenocortical hormones, the clinical manifestations of which are known as Cushing’s syndrome. Conversely, a deficiency of CRH-producing cells can, by a lack of stimulation of the pituitary and adrenal cortical cells, result in adrenocortical deficiency. (These conditions are discussed below.)
- Growth hormone-releasing hormone (GHRH) is a large peptide. A number of forms have been described that differ from one another only in minor detail and in the number of amino acids (varying from 37 to 44). Unlike the other neurohormones, GHRH is not widely distributed in other parts of the brain. It is stimulated by stresses, including physical exercise, and secretion is blocked by a powerful inhibitor called somatostatin (see below Somatostatin). Negative feedback control of GHRH secretion is mediated largely through compounds called somatomedins, growth-promoting hormones that are generated when tissues are exposed to growth hormone itself.An excess of circulating growth hormone in adults leads to a condition called acromegaly. Rarely, a benign tumour, called a hamartoma, located in the hypothalamus may produce excessive amounts of GHRH, leading to acromegaly. Equally rare are tumours arising in the islets of Langerhans of the pancreas that may secrete excessive quantities of GHRH. Indeed, GHRH was first successfully isolated and analyzed from such an ectopic (abnormally positioned) hormone-producing tumour. Isolated deficiency of GHRH (in which there is normal functioning of the hypothalamus except for this deficiency) may be the cause of one form of dwarfism, a general term applied to all individuals with abnormally small stature.
- Somatostatin refers to a number of polypeptides consisting of chains of 14 to 28 amino acids. The name was coined when its discoverers found that an extract of the hypothalamus strongly inhibited the release of growth hormone from the pituitary gland. Somatostatin is also a powerful inhibitor of pituitary TSH secretion. Somatostatin, like TRH, is widely distributed in the central nervous system and in other tissues. It serves an important paracrine function in the islets of Langerhans, by blocking the secretion of both insulin and glucagon from adjacent cells. Somatostatin has emerged not only as a powerful blocker of the secretion of GH, insulin, glucagon, and other hormones but also as a potent inhibitor of many functions of the gastrointestinal tract, including the secretion of stomach acid, the secretion of pancreatic enzymes, and the process of intestinal absorption. Despite these multiple, widespread actions, the term somatostatin has persisted because of its major role as a regulator of GH secretion, and impaired somatostatin secretion may cause some forms of hypersecretion of growth hormone.No examples of somatostatin deficiency have been found, but a tumour called a somatostatinoma has been well characterized in a number of patients. Persons with a somatostatinoma have cramping abdominal pain, persistent diarrhea, a mild elevation of blood glucose levels, and sudden flushing of the skin.
- Prolactin-inhibiting and releasing hormones – The hypothalamic regulation of prolactin secretion from the pituitary is different from the hypothalamic regulation of other pituitary hormones in two respects. First, the hypothalamus primarily inhibits rather than stimulates the release of prolactin from the pituitary (the hypothalamus stimulates the release of all other pituitary hormones). Thus, if pituitary cells are removed from the influence of the hypothalamus, few or none of the pituitary hormones are secreted, except for prolactin, which continues to be secreted by the prolactin-secreting cells (lactotrophs). Second, this major inhibiting factor is not a neuropeptide, but rather the neurotransmitter dopamine, a fact exploited in afflicted persons by physicians who are able to reduce abnormally high concentrations of prolactin by using drugs that mimic the prolactin-inhibiting effects of dopamine. Another prolactin-inhibiting factor (PRF) comes into play primarily during pregnancy and lactation. Prolactin-stimulating factors also exist, among them TRH.Prolactin deficiency is known to occur, but only rarely. Excessive prolactin production (hyperprolactinemia) is a common endocrine abnormality, and the prolactinoma is the most frequently encountered pituitary tumour.
- Gastrointestinal neuropeptides – Although modern endocrinology began with the discovery that a substance, secretin, secreted into the blood from the cells lining the gastrointestinal tract stimulates the secretion of pancreatic juices, little attention was subsequently paid to gastrointestinal hormones. When investigators began to examine the distribution of neuropeptides within the body, however, there emerged a bewildering variety of these hormones, not only within the brain but also in the lining of the gastrointestinal tract and in other organs. The list includes glucagon, the enkephalins, secretin, cholecystokinin, gastrin, calcitonin, angiotensin, substance P, pancreatic polypeptide, neuropeptide Y (a human variant of a peptide called bombesin), delta-sleep-inducing peptide, and vasoactive intestinal peptide. The actions and interactions of these hormones both in the intestinal tract and in the brain are complex and are the subject of continuing investigations. Briefly, these peptides play important roles in the transmission and inhibition of pain stimuli, in eating and drinking behaviour, in memory and learning, in the regulation of body temperature, in the induction of sleep, and in sexual behaviour.