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Definition of Endocrinology:
The study of hormones secreted by specialized glands that are ductless is known as endocrinology. Hormones are special chemical messengers constantly present in circulation. The organ/tissue on which the hormone acts is known as target organ. The hormones carry chemical messages to almost all the parts of the body (Fig. 6.1) and hence are important along with nervous system for regulation of functions of the body.
Apart from the hormones, certain other chemical signals are also secreted by cells.
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These are termed as:
a. Autocrine
b. Paracrines
c. GI tract hormones
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Autocrines are chemical signals produced by the cell and influences the activity of the cell itself (Fig. 6.2). Autocrine effects are more important for growth and sustenance of cancer cells. In a hostile environment, normal cells cannot grow but the cancer cells grow and proliferate.
Paracrines are chemical signals produced by a cell and diffuse in the surrounding area and act on the cells in the vicinity without entering circulation (Fig. 6.3). Somatostatin which regulates the secretion of insulin and glucagon in pancreas is a classical example for paracrine.
GI tract hormones are not included under classical endocrinology. The hormones of GI tract act on the structures in the GI tract and alter the secretion and movements.
The hormonal functions in the body are:
i. Regulation of the metabolism
ii. Regulation of water and electrolyte content
iii. Help for growth
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iv. Also necessary for the reproduction
v. In certain situations, they help the body to withstand the stressful stimuli.
The endocrine glands are present in different parts of body. Few of them are paired like adrenals and the others are unpaired like pituitary (Fig. 6.4).
i. Hypothalamus
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ii. Anterior and posterior pituitary
iii. Islets of Langerhans
iv. Adrenal cortex and adrenal medulla
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v. Thyroid
vi. Parathyroid
vii. Testes/ovaries
Essential endocrine glands mean without the secretions from these glands the basic survival of the person is not possible.
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The essential endocrine glands in the body are:
i. Parathyroid
ii. Adrenals
Chemical Nature:
The biochemical nature of the hormone can be:
i. Peptide/protein
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ii. Steroid
iii. Amino acid derivatives
Peptide hormones can never be given orally as they get digested in the intestine.
1. Amino acid derivatives—thyroxin, catecholamine
2. Protein—insulin
Peptides—glucagon, parathyroid hormone, pituitary hormones
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3. Steroids—hormones of adrenal cortex, sex steroids
Transport:
Hormones are circulated in bloodstream in two forms:
i. Free form
ii. Protein bound form (with plasma proteins).
The amount of free form in circulation is very less but still is important as it exerts all the biological actions of the hormone. The protein bound form acts as a reservoir and gets released into free form as and when required. Apart from this, the protein bound form cannot get filtered in the kidneys and hence hormones loss from the body is minimized.
Degradation of Hormones:
Most of the hormones get metabolized in the target organs. Hormones belonging to steroid group are metabolized in the liver.
1. By the target tissue
2. By the liver/kidney—conjugated either by glucuronyltransferase system or by SO4.
Tropic Hormone:
The hormones, which are essential for the regulation of growth and secretion of some other endocrine glands, are known as tropic hormones.
All the tropic hormones are secreted by the anterior pituitary gland.
They are:
i. TSH (thyroid-stimulating hormone)
ii. ACTH (adrenocorticotropic hormone)
iii. FSH (follicular-stimulating hormone)
iv. LH (ICSH) (luteinizing hormone or interstitial cell stimulating hormone)
v. To a certain extent even growth hormone also can be considered as a tropic hormone.
The tropic hormone secretion from anterior pituitary gland is under the influence of neurohormones secreted by the hypothalamus.
Mechanism of Action:
Second messengers: Peptides and catecholamine:
i. Formation of cyclic-AMP
ii. Calcium
iii. Inositol triphosphate
iv. Diacyl glycerol
Hormones in general act as first messenger.
Proteins and peptide hormones can bind to the cell membrane receptors. Hence when they act on the receptors, in the intracellular fluid part there will be alteration in the concentration of substances, like cAMP, Ca++ or inositol triphosphate. These substances act as second messengers and exert all actions of the hormone in the intracellular fluid region.
Steroid hormones can enter the cell through the cell membrane and bind to the receptors present in the cytoplasm or the nucleus. This increases the formation of mRNA by a process known as transcription and helps for synthesizing new proteins. Thyroxin hormone binds to the receptors present on the nucleus.
Receptors:
Receptors for the hormonal actions can be present at three different places in the target organ/cells (Fig. 6.5).
1. Cell membrane bound receptors are for all peptide hormones and catecholamine.
2. Cytosolic receptors for steroid hormone group.
3. Nuclear receptors for thyroxin hormone.
Regulation of receptor number in the target organ depends on the concentration of the hormone in circulation.
Down regulation is brought about when almost all the receptors are occupied by the hormone. There will be almost nil receptors available for binding with fresh molecules of the hormone. This normally occurs in hypersecretory state of the hormone.
Up regulation occurs when less amount of hormone available for binding with the receptors. In other words, in this situation most of the receptors are free to bind with hormones. This normally occurs in hyposecretory state of the hormone. Whatever little hormone is available, the receptors want to bind with it.
Estimation of hormones:
Can be done by:
i. Radioimmunoassay
ii. Spectrophotometer methods
iii. Bioassay.
How to establish the function or actions of hormones in the body?
1. Remove the suspected gland and look for signs and symptoms.
2. Prepare an extract and inject.
3. Inject extract in larger amounts.
4. Correlate with signs and symptoms in clinical conditions
5. Synthesis.
Regulation of Secretion of Hormones:
It can be brought about by different ways.
Feedback control wherein, the concentration of the hormone in circulation regulates its own secretion by acting through the hypothalamus or anterior pituitary or both.
The feedback control may be negative or positive. In negative feedback, increase in the free form of hormone in circulation brings about decreased secretion of the same hormone by acting through the hypothalamus or anterior pituitary gland or both, whereas in positive feedback it will be vice versa.
One of the examples for negative feedback regulation of hormone secretion is thyroxin. One of the examples for positive feedback regulation is secretion of estrogen around the day of ovulation.
Concentration of substances in plasma:
Concentration of substance in plasma can directly act on the endocrine glands and the secretory rate of the hormone may be altered, e.g. the blood glucose level regulates insulin secretion. (More is blood glucose; more will be secretion of insulin.)
Neural influences:
The activity of the nervous system can also regulate the secretion of some hormones, e.g. catecholamine and prolactin secretion is regulated by neural activity. The neuroendocrine reflex can also be included here.
Stressor influences:
They can also alter the secretion of hormones. Any sort of stress either alters the internal environment or threaten to alter the homeostasis.
Common examples of stress include:
a. Surgery, accidents, burns, etc.
b. Mental stresses, like death of near and dear ones, certain apprehensions, etc. If the stressful situation is not combated, it may become fatal. In such a situation, hormonal secretion does altered, e.g. increased secretion of Cortisol in any stress situations.
Diurnal variation:
During 24 hours of the day, the rate of hormone secretion varies depending on the time, e.g. secretion of ADH is more during the night than during daytime. Even Cortisol secretion has diurnal variation and is more during daytime when compared to night-time (Fig. 6.6).
Half-life of hormone is the time required for the hormone level to fall to 50% of its original level. The half-life varies with the hormones. Catecholamine has very less half-life of about 20 seconds whereas thyroxine has half-life of about 7 days.
The half-life of a hormone will also depend on whether the hormone is present in free form only or both in free form and protein bound form. In case the hormone is present only in free form, the duration of half-life is very less (e.g. catecholamine).
Endocrine Dysfunction:
Hyper-function:
a. Neoplastic: Benign/malignant, e.g. pituitary adenomas, cancer of any gland
b. Ectopic: SIADH, ACTH
c. Autoimmune: Graves’ disease
d. Iatrogenic: Cushing’s disease, hypo-glycaemia.
Hypo-function:
a. Autoimmune: Hashimoto’s thyroiditis, type I diabetes, Addison’s disease
b. Iatrogenic: Radiation-induced, surgical, drug- induced
c. Infectious: Addison’s disease
d. Enzyme deficiency: Especially which belong to steroid hormone group
e. Hemorrhage/infarction: Sheehan’s syndrome.