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After reading this essay you will learn about:- 1. Classification of Hormones 2. Mechanism of Action of Hormones 3. Transport and Metabolism of Hormones 4. Dose Level of Hormones 5. Duration of Action 6. Route of Administration 7. Terms Related to Hormones.
Contents:
- Essay on the Classification of Hormones
- Essay on the Mechanism of Action of Hormones
- Essay on Transport and Metabolism of Hormones
- Essay on Dose Level of Hormones
- Essay on Duration of Action
- Essay on Route of Administration
- Essay on Terms Related to Hormones
Essay # 1. Classification of Hormones:
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They are secreted from endocrine glands or group of specialised cells directly or indirectly via lymph, into the blood stream. The word hormone was introduced by Bayliss and starling in 1902 and was derived from a Greek word, ‘Harmas’ which means to excite or stimulate. Most of the hormones on secretion are transported to a distant site to exert their effect(s) upon specific tissues.
Hormones are classified according to their source, chemical nature and mode of action.
A. According to Source:
(a) Hypothalmic Hormones:
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They are secreted from groups of specialised cells located in the hypothalamus (hypothalamic nuclei) to stimulate production/ release of Anterior Pituitary (A.P.) hormones or to be stored in the posterior pituitary. Those acting upon the A.P. are either Releasing Hormone/Factor (RH/RF) or Release Inhibiting Hormone/Factor (RIH/RIF) according to their releasing or release inhibiting functions.
Current knowledge reveals that there are six releasing hormones/factors and only three release inhibiting hormones/factors produced by the hypothalamus to act on the A.P. (Fig 22.1). Those with known chemical structures and synthesised in the laboratories are better called ‘Hormones’ while others are called ‘Factors’. They are listed in Table 22.1 and are collectively known as ‘Hypothalamic Regulatory Hormones.
The hypothalamic nuclei which secrete them are under control of certain specialised cells located in the mid-brain. These specialized cells (neurons) of the midbrain secrete and release dopamine, noradrenaline and serotonin at their nerve terminals for excitation of the hypothalamic nuclei and hence are called “mono-aminergic neurotransmitter neurons.”
The mono-aminergic neurotransmitter neurons of the mid brain in-turn are under control of visceral brain which respond to environmental and emotional factors/stress.
The hypothalamic regulatory hormones are probably released in nanogrammes or still smaller quantities and under their influence the trophic hormones are released in micro-grammes, and finally the target glands release their hormones in milli-grammes. Thus there exists a cascading amplifier system to multiply and re-multiply the original hypothalamic signals.
(b) Hormones of Pituitary Gland:
Pituitary gland is present in all vertebrates but is well developed in higher animals. The anterior pituitary gland contains three types of cells viz. acidophilic, basophilic and chromophobes. The chromophobes are considered to be the cells under resting phase while the other two types supposedly secrete hormones.
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The acidophilic cells have been identified to secrete growth hormone while the basophilic cells secrete FSH, LH, ACTH, TSH and probably Prolactin also. Immuno-fluorescent microscopy has helped in identification of independent cell types for each of the hormones.
These cell types are the trophs of the hormone they secrete, and are known as Somatotrophs, Corticotrophs, Thyrotrophs and so on. The hormones of pituitary gland are listed in Table 22.2 (Fig 22.1)
The hormones of A.P. are secreted under regulatory control of hypothalamus while those of Posterior Pituitary are actually secreted by supraoptic and para-ventricular nuclei of hypothalamus and travel along the nerve fibres to be stored in the pars nervosa from where they are released on demand.
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(c) Gonadal Hormones:
All higher animals have gonads which secrete hormones and also produce germ plasm. The gonads work under the influence of trophic hormones of AP, in absence of which they undergo atrophy and degeneration. The male gonads are called testes and the female gonads are called ovaries. The hormones secreted by the gonads are listed in table 22.3.
(d) Thyroid Hormones:
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The thyroid glands present in higher animals synthesise iodinated tyrosins called Tetra-iodo- thyronine (T4), Tri-iodo-thyronine (T3), Di-iodo- thronine (T2) and mono-iodo-tyrosine (T1). Out of the four iodinated tyrosins T4 and T3 are proactive/active hormones, and are released in circulation. T3 is more potent than T4 while T4 serves better as prohormone to T3 (Fig 22.2).
The ‘C’ cells of the thyroid gland secrete one hormone called Calcitonin which regulates the level of calcium, phosphorus, and partly sodium and potassium in blood.
(e) Parathyroid Hormone:
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Parathormone is the hormone secreted from parathyroid glands and possesses osteoclactic activity. Vit. D. is necessary for its action.
(f) Adrenal Hormones:
The two adrenal glands located in the abdomen close to the kidneys are actually composed of two distinct portions and have very little functional relationship with each other. The two portions are the cortex and the medulla.
The cortical portion secretes hormones to regulate blood glucose and certain minerals while the medulla secretes neuroendocrine emergency hormones. The hormones of adrenal gland are listed in table 22.4. Secretion of cortical hormones is either under the control of ACTH or free from it, while the medullary hormones is entirely free from any direct pituitary influence.
(g) Pancreatic Hormones:
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The islet cells of panaceas secrete two hormones namely insulin and glucagon which regulate carbohydrate metabolism of the body.
(h) Local Hormones:
In addition to the hormones stated above the body secretes a number of other hormones and like substances which together are grouped as local hormones or local chemical messengers. Examples are-Gastrin, Secretin, Pancreozymin, Colecystokinin, Chorionic gonadotrophin, Thymic hormone, Acetylcholine and noradrenaline. However, some of them play bigger roles also.
B. According to Chemical Nature:
(i) Protein/Peptide Hormones:
Hypothalamic, Pituitary, Thyroidal, Para-thyroidal, Pancreatic, Adrenomedullary and Gut hormones fall under this group.
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(ii) Steroid Hormones:
Gonadal hormones and Adrenocortical hormones are steroid ones.
C. According to Mode of Action:
(a) Kinetic Hormones:
Those which are secreted by neural means, stimulate smooth muscles, have very short half-life time in plasma; and their secretions are regulated by neural feed back loop. Examples are oxytocin and catacholamines.
(b) Metabolic Hormones:
Those which regulate the chemical mechanisms of the body. Examples are Insulin, Glucagon, Parathormone, Calcitonin, Thyroxin etc.
(c) Endocrinokinetic Hormones:
Those which act upon another endocrine glands to produce the desired hormones for action. Examples are Trophins.
Essay # 2. Mechanism of Action of Hormones:
(a) Location of Receptors:
Hormones exert their actions on different target cells after combining with specific receptors. These receptors may be either membranous (Fig 22.3) cytoplasmic or nuclear (Fig 22.4) All protein hormones except thyroid hormone have their receptors in the cell membrane, while receptors for steriod hormones are located in the cytoplasm and those for the thyroid hormones are in the nucleus.
Protein and peptide hormones can not enter into the cell, hence they act through a second messenger (Fig. 22.3) which may be cAMP, cGMP, Calcium calmodulin or Phosphoenositoids.
However, the second messengers for insulin, growth hormone etc. are not known. Steroids and Thyroid hormones need no second massagers because they are lipid soluble and pass through the cell membrane to bind with the cytoplamic receptors (Fig 22.4).
(b) Mechanism of Action:
(i) Mechanism of action through second messenger (cAMP system): On reaching to the target cells protein hormone(s) combine with its specific receptor present in the membrane. The hormone-receptor complex activates or inactivates adenyl cyclase through stimulatory or inhibitory action of G-protein (Fig 22.5).
The activated adenylcyclase converts cytoplasmic ATP into cyclic AMP, which then works as the second messenger while the hormone itself remains as the first messenger. The cAMP so formed then activates a chain of enzymes (Fig. 22.3, 22.5, 22.6).
Adenyl cyclase stimulates G-Protein for stimulatory activity of hormones like ACTH, ADH, β-adrenergics, Calcitonin, CRH, FSH, Glucagon, HCG, LH, LPH, MSH etc. while It inhibits the G-protein activity for action of acetylcholine, α2-adrenergics, angiotensin-II, opioids and somatostatin.
(ii) Gene Activation:
Some hormones because of their low molecular weight and lipid solubility, diffuse through the cell membrane of their target cells and combine with the specific cytoplasmic receptor proteins to form a hormone receptor complex. This complex then undergoes a process of conformational changes, called activation and enters into the nucleus.
The complex activates transcription of specific DNA to form messenger RNA (m RNA) which then diffuses into the cytoplasm and promotes transcriptional process at the ribosomal level to form new protein (Fig. 22.4). Steroids and Thyroid hormones work by this way.
(c) Overall Effect of Hormones Complex:
The overall affect of hormone may be summarized as below:
(i) The plasma membrane permeability may be increased to glucose and amino acids. e.g. Insulin.
(ii) The hormone may increase ion fluxes. Aldosterone promotes Na+ influx into the distal convoluted tubular cells and increases efflux of K+ and H–.
(iii) It may increase permeability to water. ADH-receptor complex behaves this way and increases permeability of the cells of distal convoluted tubule and collecting ducts for resorption of water.
(iv) It may affect cell metabolism by changing the activity of rate limiting enzymes.
(v) The hormone often promote protein synthesis at different sites by – (a) increased entry of amino acids into the cell. (b) enhanced nuclear transcription (c) enhanced ribosomal transcription. Steroid and Thyroid hormones behave this way.
(vi) Some hormones induce multiplication and or enlargement of their target cells (hyperplasia and hypertrophy). Growth hormone is an example of this category.
Essay # 3. Transport and Metabolism of Hormones:
Protein hormones are usually stored within the glands which produce them, however, they are released into the efferent blood vessels on demand. But the steroid hormones are released with production and are not stored. Hormones are carried in the plasma partly bound to protein(s) and partly in free form.
Plasma contains specific carrier protein for steroid hormones and thyroxin, and are termed as corticoid binding-globulin (CBG/Transcortin), sex-hormone binding globulin (SHBG) and Thyroxin binding globulin (TBG). The protein bound hormone is inactive and probably serves as stored buffer stock. The free hormone(s) is active and is actually responsible for hormonal activity at the target cell (s).
Liver is mainly responsible for metabolism of the hormones. However, they are also metabolised in the target endocrine glands and in the tissues on which they act. Liver conjugates the hormones to make them inactive or less active, but sometimes metabolic transformation is necessary for certain hormone to make them biologically active.
Example of such metabolic transformation is that of testosterone which when converted into dihydrotestosterone becomes active. Hormones conjugated, degraded and traces of free ones pass out through the kidneys to appear in the urine.
Essay # 4. Dose Level of Hormones:
It is well understood that under physiologic conditions hormones are released in very small amounts. Release or administration of exogenous hormone in any higher amount may affect the physiological status of the individual.
Therefore, it is highly essential that the dose level (critical dose) be decided judiciously by the clinicians. It would be harmful if a clinician depends only upon the hormone selected and not upon its dose.
For example, in dairy cows progesterone in small amounts would act as ovulatory hormone while the same in large amounts would block ovulation. Similarly estrogen in small amounts during lactation period would favour lactation by stimulating lactiferous tissues while the same hormone in larger doses would suppress milk secretion.
Essay # 5. Duration of Action:
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Hormones are biologically active within the body till its half-life-time and each hormone has its own half life time. The half life time of hormones vary considerably. For example, progesterone has a half-life-time of 4 minutes, ACTH that of 6 minutes and the same of thyroxin is 10 days. The half-life-time is also an indication of the rate of elimination of that hormone.
In recent years attempts have been made to prolong the half-life-time of hormones for longer period of action. Advancement in chemistry has made it possible. Synthetic analogues of hormones have been prepared which resemble the natural hormone but differ slightly in structure.
Such alteration in structure reduces their metabolic rate of destruction but considerably maintains the selectivity to combine with specific receptors. For example, the acetylated steroids undergo slow metabolism because of lack of destructive enzymes in the system. The slow destruction of analogues lead to its prolonged half life time in the body and thereby increased duration of biologic activity.
Essay # 6. Route of Administration:
It is an important factor in consideration of on set of action of hormones. Intravenous administration of a hormone no doubt gives fastest response but is not usually adopted. This is followed by intra-peritoneal (I.P.) intramuscular (I.M), subcutaneous (S C) and oral routes. Selection of route to administer a hormone should be made judiciously since certain hormones do not respond when administered orally.
For example, protein hormones administered orally are degraded in the digestive system and made inactive. The technique of transplantation of hormones under skin is of considerable importance in veterinary practice.
It is a modified subcutaneous administration technique where hormones are deposited under the skin along with a slowly disintegrating filler, which permits slow absorption of the hormone for a longer period.
Essay # 7. Terms Related to Hormones:
i. Antagonists:
Active hormones are called agonists while the molecules which block the action of hormones are called antagonists. Antagonists combine with the receptors of agonists and block the latter from exhibiting response. For example spironolactone is anti-mineralocorticoid and cyproterone is an anti-androgen.
ii. Augmentation:
Protein hormones when administered undergo fast metabolic changes to become inactive/less active, but the same when combined with certain ions like zinc, copper, iron of heme withstand the metabolic degradation/alteration for a longer period and exhibit prolonged response.
For example, insulin as such has a very short half life time but when combined with zinc become stable to withstand fast enzymatic degradation and exhibit prolonged action.
iii. Synergism:
When more than one hormone is administered simultaneously they may exhibit a response greater than the sum of the responses of the same hormones had they been administered separately. This phenomenon is called synergism. FSFI and LPI/ICSH form a good example of hormonal synergism.
