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Essay on Endocrinology

Essay Contents:

  1. Essay on the Definition of Endocrinology
  2. Essay on the History of Endocrinology
  3. Essay on the Science of Endocrinology
  4. Essay on the Nature of Hormones
  5. Essay on the Endocrinology and Medicine
  6. Essay on the Hormones and Homeostasis
  7. Essay on the Functional Interactions of Hormones
  8. Essay on the Neuroendocrine Integration
  9. Essay on the Regulation of Endocrine Functioning
  10. Essay on the Metabolism of Hormones
  11. Essay on the Interaction between Hormones

Essay # 1. Definition of Endocrinology:

Endocrine or ductless glands secrete hormones into the extra cellular space surrounding them. These hormones enter the circulatory system and are distributed to the target sites. ‘Endocrinology’ is the study of the ductless glands or tissues and their hormonal products.

Hormones are considered to be synthesized within specific endocrine organs and then secreted into the blood stream to act on specific target sites some distance away to evoke a physiological response.

However, there are large numbers of exceptions to this definition. For example, secretin like peptide is produced by nerve cells within brain and it acts on adjacent or nearby neurons without being transported by the blood stream. Such substances, which act as local messengers, are known as local hormones.

Essay # 2. History of Endocrinology:

Endocrinology is relatively a recent science. It began with the first recorded experiment on hormones by Berthold in 1849. For the next forty years, there were no significant developments.

From 1910 onwards there were quick advances and the outlines of vertebrate and invertebrate endocrine system were well worked out by 1950. In later stages, chemistry played a very important role in the advancement of endocrinology, and many important contributions have been made in this field.

The history of endocrinology is based on simple observations to complex experiments. In Nineteenth century, although details of the microscopic structure of many tissues and glands were described, the functional significance of the endocrine glands was not known. Clinical correlations between tissue and organ abnormalities such as atrophy or enlargement, and changes in particular physiological states were noted.

The effects of removal of tissues or organs on the physiological functions have been studied. This was followed by transplantation of tissues and use of extracts of tissues to determine whether they serve as adequate replacement therapy for the absent tissue. Hormones were discovered by purification of the physiologically active tissue extracts and identification of the active principle.

Berthold (1849) noted that castration of cockerels led to non-development of their combs and wattles, and failure to exhibit male dominant behaviour. Replacement of the testes led to the development of the comb and wattles, and exhibition of male behaviour consisting of showing interest in hens and aggressiveness towards other males. If a single testis was replaced, its size was larger than usual.

This led to the discovery of compensatory hypertrophy, an increase in the size of an organ to compensate functionally for the activity of the other lost organ. Berthold speculated that testes secreted some substance that entered the blood and acted on the body of the cockerel to develop male characteristics.

However, this was not proved for a long time until it was shown that extracts of testes in a castrated male could functionally replace the testes. Testosterone was purified and crystallized in 1935. Bayliss and Starling (1902) demonstrated that a substance produced by the intestinal mucosa stimulated the secretion of pancreatic juice. The active substance was named as secretin. The term hormone was first introduced by Starling in 1905 (Greek: I excite).

Von Mering and Minkowski showed the relationship between pancreas and diabetes mellitus in 1889. They noted that removal of pancreas from dogs led to diabetes. Banting and Best (1922) suggested that the islets of Langerhans of pancreas are essential in the control of carbohydrate metabolism and they regulate blood glucose levels by producing an internal secretion.

Administration of the extracts of pancreatic islets to diabetis dogs decreased the blood glucose level significantly. The name insulin to the pancreatic hormone was given by Schaefer in 1912.

Loewi (1921) demonstrated the release of chemical messengers by nerves. His experiment on frog heart proved that vagus nerve released substances that affect the relaxation and contraction of cardiac muscle. The inhibitory substance was identified as acetylcholine and the accelerator substance as norepinephrine. Loewi was awarded the Nobel Prize for this work.

The characterization and amino acid sequence of the hormone, insulin was established by Sanger in 1953 for which he received Nobel Prize. The hormones first synthesized were oxytocin and vasopressin. Du Vigneaud synthesized them in his laboratory for which work he was also awarded Nobel Prize.

Discovery of Cyclic AMP:

Sutherland and coworkers showed that hormones stimulate fragmented cell membrane preparations to activate the enzyme, liver phosphorylase, which catalyzes the breakdown of liver gycogen.

They demonstrated that when hormones were incubated with cell membrane fragments, a factor which in turn activates the phosphorylase enzyme present in the supernatant fraction of the tissue homogenate was released. This substance was identified by Sutherland as cyclic Adenosine Mono Phosphate (cAMP).

Sutherland and his coworkers in 1962 discovered the presence of cyclic AMP in biological materials and the enzyme adenyl cyclase, which is responsible for production of cyclic AMP in cells. For this important work, Sutherland received Nobel Prize in Medicine or Physiology in 1971. Cyclic AMP, known as second messenger of hormone action is involved in the actions of many hormones and other stimuli on physiological processes in cells.

Discovery of Neuropeptides:

An important milestone in the history of hormones is the discovery of the control of pituitary gland by a specialized area in brain called as the hypothalamus. Harris (1955) showed that the release of the pituitary hormones is controlled by certain humoral factors released by hypothalamus. Later Vale et al (1977), Setalo and Flerko (1978) and Moss (1979) noted that extracts of the hypothalamus contained some substances that effected the release of pituitary hormones.

Schally and his coworkers in 1978 collected as many as 2,50, 000 hypothalami of pigs and extracted the substance that stimulates the release of thyroid stimulating hormone from the pituitary gland. Guillemin (1978 at the same time isolated similar factor from the brains of sheep.

The structure of the two substances was identical. This work was followed by the isolation and structural identification of hypothalamic hormones controlling the secretion of growth hormone and pituitary gonadotropins.

The work of Schally and Guillemin on the chemical structure of gonadotrophic hormone releasing hormone (GnRH) in pigs and sheep showed their identical nature. Synthetic GnRH and analogs are now used in controlling the fertility of animals and human beings.

Antihormones analogs can be used as contraceptive agents. Guillemin and his colleagues (1982) discovered the structure of somatostatin, which inhibits the secretion of pituitary growth hormone. This discovery in later years has proved to be of much importance in medicine.

Guillemin and Schally for their contribution in the structure determination and identification of hypothalamic regulatory peptides have received Nobel Prize in Physiology and Medicine in 1978. Many other chemists and endocrinologists contributed important discoveries that facilitated the determination of the structure and functions of hypothalamic peptide hormones.

Nerve growth factor, a peptide hormone required for the growth, development and maintenance of certain nerve cells of brain and peripheral nervous system was discovered by Rita Levi-Montalcini and Stanley Cohen discovered epidermal growth factor, another peptide hormone which stimulates differentiation and growth of epithelial cells.

For these discoveries, they received Nobel Prize in Medicine and Physiology in 1986. Important new information in endocrinology is being generated at a very fast pace in recent years. The molecular mechanisms of the action of peptide and steroid hormones are being elucidated.

Essay # 3. Science of Endocrinology:

Endocrine glands secrete their products, the hormones into the adjacent extracellular space from where they enter the circulatory system. Endocrine or ductless glands differ from the exocrine glands like salivary glands whose products are released into the ducts that lead to the digestive tract and then to the exterior of the body. ‘Endocrinology’ is the study of the ductless glands or tissues and their hormonal products.

Endocrine system possesses no structural unity. Endocrine cells are scattered all over the body. They may form well organized and defined glands elaborating one or several hormones, or be present as tissues, or as individual cells. Endocrine cells and glands originate embryologically from all types of tissues including the nervous tissue.

Hormones were originally considered to be synthesized within specific endocrine organs and then secreted into the blood stream to act on specific target tissues, some distance away to evoke a specific physiological response.

Transport of hormones by systemic blood circulation implies high dilution. In some instances this is avoided by the development of fairly direct vascular connections between the endocrine cells and the target cells of the hormones.

A well-known case is the portal circulation between hypothalamus and hypophysis, which carries the hypothalamic hormones to the pituitary. Cells or tissues may secrete specific substances that act over short distances on adjacent cells or tissues.

This type of humoral transport does not involve the blood and takes place by diffusion of substances in intercellular or interstitial spaces or by other local transport mechanisms. Prostaglandins, kinins and others belong to this functional type. Their influence can merge with the direct effect of neurons on their target cells.

Essay # 4. Nature of Hormones:

Hormones are synthesized and secreted by living endocrine glandular cells within the body or in cultures of endocrine cells in vitro. A hormone is usually transported by the blood stream from endocrine cells to serve as a ‘chemical messenger’ that acts in a specific way on the target cells or tissues.

A hormone does not provide energy or building material but it exerts profound regulatory effect on growth, differentiation and metabolic activities of the target cells by effecting on membrane permeability, activation/ deactivation of enzymes, formation of cyclic AMP, etc.

Chemically, hormones form a group of heterogeneous substances. Some are steroids (e.g., adrenocortical hormones, and sex hormones). Many hormones are proteins or polypeptides.

They may be stored as granules for hours or days and are released by exocytosis. The anterior pituitary hormones, hypothalamic hormones, parathyroid, calcitonin, insulin, glucagon, gastro­intestinal hormones (secretin, gastrin, etc.) and posterior pituitary hormones are all peptides.

Some of the hormones are derivatives of aminoacids. Thyroxin and tri-iodo thyronin are iodinated derivatives of the amino acid tyrosine. Similarly, adrenaline and nor-adrenaline are also derived from tyrosine.

In the blood stream many hormones are bound to specific plasma carrier proteins. This binding forms a reservoir from which hormones are released and diffuse to act on the target cells. However, catecholamines are not bound to plasma proteins and have a short half-life in blood for a few minutes. Thyroxin on the other hand, bound to carrier proteins has a long biological half-life.

Hormones are inactivated partly in the target organs and in liver where chemical degradation and conjugation occur. Examples are insulin, adrenaline, many steroids, and thyroid hormones.

Hormones exert their physiological effects when present in very small quantities in blood and other body fluids. Steroids and thyroxin act at concentrations of 10-6 to 10-9 moles per liter of blood while peptide hormones are effective at 10-10 to 10-12 moles per liter. Due to such extremely low concentrations it is difficult to detect them in blood and tissues, and specific very sensitive methods have been developed to detect and quantitatively estimate them.

Some hormones do not have specific target cells or organs and therefore affect all or almost all the cells of the body. Thus, growth hormone influences growth and development of all parts of the body.

Most of the hormones, however have specific target sites or tissues on which alone they exert their effects, because only these tissues have specific receptors that bind with the hormones to initiate their actions. For example, adreocorticotropin secreted by anterior pituitary stimulates the adrenal cortex to produce adrenocorticosteroid hormones.

Essay # 5. Endocrinology and Medicine:

It is well known that deficiency or excess of hormones in human body and other animals leads to clinical disorders. Deficiency diseases like diabetes, can be cured by the external supplementation of the requisite hormone. However, many of the hormones are not available in large quantities to fulfill the medical requirement of human beings.

Therefore, it becomes necessary to synthesize the required hormones in large quantity. For synthesizing hormones, knowledge of comparative hormone structure is essential so that structural analog, with biological activity may be produced.

Sometimes, the structure of a hormone like somatotrophic hormone, which controls the normal growth of human beings, is very large to be synthesized. Under such circumstances, if the structure of the hormone, and the part in which its biological activity lies are known, it becomes easier to synthesize the hormone in large quantities.

Introduction of the human STH gene into bacteria by recombinant DNA technology provides a method for the large-scale production of the hormone. Similarly, characterization and synthesis of hypothalamic releasing factors or hormones can act as a medically important tool for stimulating pituitary hormones.

Essay # 6. Hormones and Homeostasis:

The concept of homeostasis was first formulated by the French physiologist Claude Bernard in 1974. Organisms live in two environments, the external environment surrounding the organism and the internal environment within the cells of the body. The internal environment is the fluid medium within the cells and surrounding the cells.

Organisms become independent of the changes that occur in the external medium by controlling the internal medium. Thus, the internal medium is maintained at a constant level. Cannon (1960) coined the term homeostasis to include all the physiological processes, which maintain most of the steady states in the organism.

These are complex and involve brain and nerves, heart, lungs, kidneys and spleen, all working in a coordinated and cooperative fashion. In mammals a constant level of glucose, calcium, sodium, and other constituents is maintained in the body fluids.

Small fluctuations in the concentration of these constituents occur during different time periods of the day, in different seasons, different stages of development, age, and reproductive periods of the animal.

i. Feedback Systems:

The body maintains control over the concentrations of substances like glucose, calcium and sodium ions in body fluids with the help of certain sensory cells, which have a definite set point for monitoring the concentrations of these substances.

If the concentration of a metabolite like glucose is lowered in body fluids due to loss in urine, the receptor cells become activated and respond by releasing a hormone or some other substance, which in turn acts on other cells to release their stored metabolite or prevent the loss of the metabolite from the body so that the concentration of the metabolite is raised to the requisite level.

Shutting off the release of the hormone by the receptor cells prevents increase in the concentration of the metabolite like glucose above a critical level. Such a type of mechanism in which increase in the concentration of the metabolite inhibits the release of the hormone is known as negative feedback mechanism.

In contrast to the negative feedback mechanism, rising concentrations of a hormone act on another gland to release a second hormone, which further stimulates the secretion of the first hormone. This is known as the positive feedback mechanism.

Positive feedback systems have some mechanism to shut the release of the first hormone otherwise the system will continuously go on increasing in amplitude. A gonadal hormone estradiol increases the release of pituitary gonadotropins, which in turn stimulate ovarian estrogen production. Thus estrogen and gonadotropin levels go on increasing continuously.

Negative and Positive Feedback Systems

In the monthly menstrual cycle, the degeneration of the ovarian follicles, the source of estradiol results in a subsequent decrease in the plasma estrogen and gonadotropin levels. In a number of feedback systems, an increase in the plasma level of one hormone stimulates the release of a metabolite like glucose from a target tissue.

Increase in the level of the metabolite in plasma stimulates the release of a second hormone, which inhibits the release of the metabolite from the target tissue. Decrease in the level of the metabolite acts as a stimulus to the release of the first hormone.

General Scheme of Two Hormone Feedback Systems

ii. Homeostasis of Glucose:

The concentration of glucose in blood is maintained at a constant level although many factors such as, food intake, rate of digestion, excretion, exercise, reproductive state and psychological condition influence its level.

Hormonal Control of Glucose Homeostatis

All these factors affect the physiological regulatory mechanism of blood glucose level. Decrease in the level of blood glucose after muscular exercise is recognized by alpha cells in the islets of Langerhans, which release a hormone glucagon. This hormone, in turn acts on the liver cells and helps to breakdown glycogen into glucose and thus the blood glucose level is brought to the normal level.

If the blood glucose level rises after a meal, the high level of blood glucose is perceived by another type of cells in the pancreas namely, the beta cells release a hormone insulin that induces the uptake of glucose by liver cells to convert it into glycogen. This reduces the blood glucose level and brings it back to the normal level.

iii. Homeostasis of Calcium:

Calcium is required for clotting of blood, muscle contraction, cellular secretory processes and a number of other cellular functions. Blood calcium level in most of the mammals is maintained at a constant level and varies only within a very narrow range. Any fluctuation from the set concentration activates the homeostatic mechanisms to bring it back to the normal level.

Decrease in blood calcium level is perceived by parathyroid cells which release parathormone. This hormone acts on the bone to release the stored calcium. Absorption of calcium from the gut and reabsorption by urinary tubules in the kidney is favoured so that the blood calcium level is brought back the original level.

Elevation of calcium level above the normal level after consumption of food leads to the release of another hormone, calcitonin from the thyroid gland. Calcitonin promotes deposition of calcium in the bone and reduces the absorption of calcium in the gut and kidney.

Essay # 7. Functional Interactions of Hormones:

In the normal functioning of the body few processes under hormonal control are regulated by only one hormone. Similarly only few hormones perform only one role. In other words, a hormone may have many functions and body processes are not regulated by only one hormone but many hormones may regulate one process.

i. One Function – Many Hormones:

For normal brain functioning it is very important that a regular and constant supply of oxygen and glucose are essential. Hormones maintain cerebral glucose supply and four important processes, namely food ingestion, hepatic glycogenolysis, gluconeogenesis and glucose sparing by other tissues are involved.

Each of these processes is controlled by hormones. Food intake and appetite are regulated by Cortisol while intestinal absorption of glucose is regulated by thyroxin. Secretion of Cortisol is influenced by Adrenocoticotropin (ACTH) and Corticotropin Releasing Factor (CRF) respectively.

Glycogenolysis involves breakdown of hepatic glycogen to glucoses- phosphate and finally to glucose. This process is influenced by three hormones. Glucagon from pancreas stimulates the glycogen breakdown, and the falling level of insulin promotes the process. Epinephrine plays a small role in stimulating glycogenolysis. Gluconeogenesis helps to maintain blood glucose level during fasting.

The production of glucose from amino acids, glycerol and lactate can sustain the blood glucose level for weeks or months. Gluconeogenesis is stimulated by Cortisol, glucagon and growth hormone.

The maintenance of a single circulating metabolite, blood glucose, involves the participation of atleast 10 hormones and 6 endocrine glands. The relations between the hormones can be additive, cooperative or opposing. Unless the entire system is considered, it is not possible to understand the process.

ii. One Hormone – Multiple Actions:

This type of mechanism in which a hormone produces many effects is found only in a few cases. For example insulin promotes entry of glucose into muscle and adipose tissues; affects both glycogenolysis and gluconeogenesis; regulates lipolysis and favors the synthesis of muscle proteins. Similarly epinephrine is involved in promotion of glycogenolysis and peripheral lipolysis. It also inhibits insulin secretion by pancreas.

Parathormone is also an example of the multiple effects of a hormone. This hormone stimulates release of calcium and phosphate from bone, promotes reabsorption of calcium by the renal tubule, and stimulates the synthesis of the biologically active form of vitamin D. All these actions increase the blood calcium level.

Essay # 8. Neuroendocrine Integration:

The nervous and endocrine systems work in close union and mediate the process of physiological adaptation to the environmental stress. Reactions mediated by the nervous system are faster and are more important immediate responses as compared to the hormonal effects, which serve to complete a homeostatic adaptation. Neural influences play a major role in uniting the responses of the endocrine glands.

The interaction between the nervous system and endocrine glands can be differentiated into three types:

(i) Regulation of the functioning of pituitary gland by hypothalamus,

(ii) The combination of neural, and

(iii) Endocrine responses to stimuli and the control of endocrine secretion by nervous system.

i. Hypothalamus and Pituitary Gland:

Harris and coworkers stated that the functioning of the pituitary gland is regulated by certain stimulating and inhibitory factors secreted by certain neurons in the hypothalamus.

These neurons on one end are connected to other neurons of the central nervous system through synapses while at their distal ends are secretory structures producing small polypeptides that are released directly into the hypophyseal portal system so as to reach the cells of anterior pituitary through a secondary capillary plexus.

As there is no blood-brain barrier at the hypothalamus, the circulating sodium or contisol can directly reach the regulatory sites. The hypothalamus lodges centers for crucial functions such as thirst, hunger, blood pressure, osmoregulation, and pulse rate.

The portal circulation allows very minute quantities of substances released by the hypothalamus to reach the pituitary gland. It has been experimentally demonstrated that the pituitary secretions control the onset and depth of sleep, vision and smell.

ii. Autonomic Nervous System:

The integration between the nervous system and endocrine glands is exemplified by the regulation of blood pressure by the two systems. The intravascular volume and vascular tone determine blood pressure.

Intravascular volume is controlled by sodium and water balance, which in turn is influenced by vasopressin, Cortisol, angiotensin, and aldosterone. Vascular tone is regulated by sympathomimetic amines but vascular sensitivity to catecholamines is influenced by both Cortisol and thyroxin (T4).

iii. Control of Endocrine Function by Nerves:

Regulation of the functioning of the endocrine cells by nerves provides a means of cooperative response to different challenges. Adipose tissue cells are innervated by both α- and β -adrenergic nerve fibers and lipid synthesis as well as breakdown is partly controlled by adrenergic impulses.

In the hypothalamo-pituitary complex, α-adrenergic impulses release growth hormone (GH) and inhibit prolactin (PRL), whereas β-adrenergic impulses inhibit GH release. The parathyroid gland is also innervated by autonomic nerve supply. β-adrenergic stimulation increases the levels of cAMP and promotes parathyroid hormone release. In pancreas stimulation of α-adrenergic fibers inhibits insulin release.

Peripheral neuroendocrine regulation is of short-range responsiveness and allows for adaptation to changes in posture and stressful conditions. Central neuroendocrine patterns, in contrast have longer time duration ranging from the diurnal rhythm of ACTH to the monthly cycles of gonadotrophic hormones.

Essay # 9. Regulation of Endocrine Functioning:

The three major groups of hormones namely, steroid, peptide and amino acid hormones have different span of biological half-lives. Steroid hormones have half-lives ranging from 60 to 100 minutes while protein hormones in unbound form have half-lives varying between 5 to 60 minutes. The amino acid hormones are intermediate between the two groups.

Thyroxin attached to three binding proteins has a half time of about a week whereas epinephrine is active unto less than a minute. Very little information is available on the basal secretion of endocrine glands when the glands are not stimulated and in the absence of a homeostatic mechanism. In vitro studies have shown that the parathyroid glands secrete certain amount of parathormone even when the concentration of serum calcium is very high, and even in the absence of a stimulation.

Neuroregulation is a principal determinant of basal secretion by the hypothalamo-pituitary complex. ACTH secretion shows a diurnal rhythm depending on variable stimulation by the hypothalamus. This rhythm is not dependent on CRF but reflects a hypothalamic electrical pattern.

GH and PRL are released in a sharp burst within one hour of the onset of deep sleep. These rhythmic releases are believed to be secondary to central nervous stimulation mediated through hypothalamic releasing factors.

Essay # 10. Metabolism of Hormones:

Continuous exposure of tissues to active hormones can be regulated by metabolic degradation of the circulating hormones. During the metabolism of hormones, the molecule may be altered, consumed at the site of action and excreted through bile or urine.

Among the steroid hormones, Cortisol is successively reduced to di and tetrahydrocortisol in liver under the influence of thyroxin; it is further converted into the weak androgen, androsterone and etiocholanalone. Peptide hormones have very short half-lives. They are digested and converted into individual amino acids in lysosomes.

Essay # 11. Interaction between Hormones:

A hormone can influence the synthesis, action, transport and metabolism of another hormone. Adrenaline is synthesized in adrenal medulla from the amino acid tyrosine. Norepinephrine is methylated under the influence of the enzyme phenyl ethanolamine -N -methyl transferase. This enzyme is induced by Cortisol secreted by the adrenal cortex.

Certain hormones stimulate the receptors of other hormones. Estrogen induces a progesterone binding protein in the uterine myometrium and endometrium. Estrogen prepares a receptor for the progesterone. Triiodothyronine induces certain β-adrenergic receptors leading to decrease in the effectiveness of catecholamines. The physiological action of a hormone is dependent upon the other hormones present and the metabolic state of the individual.

Hormones can influence the transport proteins of other hormones. T4 and Cortisol are circulated in blood in a bound form attached to thyroxin binding globulin (TBG) and corticosterone binding globulin (CBG). The level of each of these proteins is elevated by estrogen. Decrease in the level of free hormone increases the production leading to a new steady state.

Non-endocrine tissues also play an important role in the metabolism of hormones forming a source of regulation of the levels of hormones and also as a cause of disease. Production of estrogen in the postmenopausal women is an example of this phenomenon. The adrenal androgen androstenedione can be converted into estrone in liver and adipose tissue. This leads to endometrial or breast cancer due to excessive production of estrone in obese women.

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