Endocrine System
62. General principles of hormonal regulation. Chemistry of hormones. Storage and secretion of hormones.
Mechanisms of hormonal action.
63. Function of the anterior pituitary gland. Control of pituitary secretion by the hypothalamus.
Physiological functions of growth hormone.
64. The posterior pituitary gland and its relation to the hypothalamus.
Physiological function of antidiuretic hormone and oxytocin.
65. The thyroid gland. Functions of the thyroid metabolic hormones.
Regulation of thyroid hormone secretion.
66. Parathyroid hormone, Calcitonin, calcium and phosphate metabolism.
67. Endocrine function of the pancreas. Insulin and its metabolic effects.
Glucagon and its functions. Regulation of the blood glucose concentration.
68. The adrenal glands. Functions of the mineralocorticoids.
69. The adrenal glands. Functions of the glucocorticoids.
70. Adrenal androgens. Abnormalities of adrenocortical secretion. The prostaglandins.
71. Reproductive and hormonal function of the male. Functions of testosterone.
Control of male sexual functions by hypothalamus and anterior pituitary gland.
72. Female physiology before pregnancy. The monthly ovarian cycle and function of the gonadotropic
hormones. Functions of the ovarian hormones. The monthly endometrial cycle and menstruation.
Interplay between the ovarian and hypothalamic - pituitary hormones.
62. GENERAL PRINCIPLES OF HORMONAL REGULATION. CHEMISTRY OF HORMONES.
STORAGE AND SECRETION OF HORMONES. MECHANISM OF HORMONAL ACTION.
General principles of hormonal regulation. The activities of cells, tissues and organs of
the body are coordinated by the interplay of several types of chemical messengers.
o Neural: neurotransmitters are released at synaptic junctions and act locally
o Endocrine: hormones released from specialized glands or cells reach the
circulating blood and influence the function of target cells some distance
away
o Neuroendocrine (neurocrine): secretion products from neurons
(neurohormones) reach the circulating blood and influence the function of
target cells some distance
o Paracrine: cell secretion products diffuse into the extracellular fluid and
affect neighbouring target cells
o Autocrine: cell secretion products affect the function of the same cell by
binding to cell surface receptors
o Cytokine: secreted cell proteins function as autocrines, paracrines, or
endocrines and often act on a broad spectrum of target cells.
Chemistry of hormones.
Chemically, hormones and neurohormones are of three types:
Proteins and peptides. Included in this group are peptides ranging from as small as three amino acids (thyrotropin-releasing
hormone) to proteins almost 200 amino acids long (growth hormone and prolactin).
Steroids. These are derivatives of cholesterol and include the adrenocortical (cortisol, aldosterone) and gonadal (testosterone,
estrogen, progesterone) hormones.
Derivatives of the amino acid tyrosine. Included in this group are hormones from the thyroid gland (thyroxine, triiodothyronine)
and adrenal medulla (epinephrine and norepinephrine).
Storage and secretion of hormones.
Protein/peptide hormones are synthesized on the rough endoplasmic reticulum in the same fashion as most other proteins.
o Initial protein formed by the endoplasmic reticulum is larger than the active hormone and is called a preprohormone.
o Signal sequence of this large protein is cleaved in the endoplasmic reticulum to form a prohormone.
o In the Golgi apparatus the prohormone is packaged in secretion granules along with proteolytic enzymes that cleave the
prohormone into active hormone and other fragments.
1
, o When the endocrine cell is stimulated, the secretion granules migrate from the cytoplasm to the cell membrane. Free
hormone and co-peptides are then released into the extracellular fluid by exocytosis.
Steroid Hormones are synthesized from Cholesterol. In contrast to protein/peptide hormones, there is little hormone storage in
steroid-producing endocrine cells.
o There are large stores of cholesterol esters in cytoplasmic vacuoles that can be rapidly mobilized for synthesis of steroid
hormones after stimulation of the steroid-producing cell.
o Once the steroid hormone appears in the cytoplasm, storage does not take place, and the hormone diffuses through the
cell membrane into the extracellular fluid.
o Much of the cholesterol in steroid-producing cells is removed from the plasma, but there is also de novo synthesis of
cholesterol from acetate.
Thyroid Hormones and Catecholamines are synthesised from Tyrosine.
o As with steroid hormones, there is no storage of thyroid hormones in discrete granules, and once thyroid hormones
appear in the cytoplasm of the cell they leave the cell via diffusion through the cell membrane.
o In contrast to steroid hormones, there are large stores of thyroxine and triiodothyronine as part of a large iodinated protein
(thyroglobulin) that is stored in the lumens of thyroid follicles.
o In comparison, the other group of hormones derived from tyrosine, the adrenal medullary hormones epinephrine and
norepinephrine, are taken up into preformed vesicles and stored until secreted.
o As with protein hormones stored in secretion granules, catecholamines are released from adrenal medullary cells through
exocytosis.
Mechanism of hormonal action.
Hormonal Receptors and their activation hormones control cellular processes by interacting with receptors on target cells. These
receptors are (1) either on or within the cell membrane, as in the case of peptide/protein and catecholamine hormones, and (2)
within the cell, in either the cytoplasm or nucleus, as is the case for steroid and thyroid hormones. Receptors are usually specific
for a single hormone. The hormone-receptor interaction is coupled to a signal generating mechanism that then causes a change in
intracellular processes by altering the activity or concentration of enzymes, carrier proteins, and so forth.
In the case of peptide/protein and catecholamine hormones that do not readily pass the cell membrane, interaction with the
receptor on or within the cell membrane often results in generation of a second messenger, which in turn mediates the hormonal
response.
Often, coupling G-proteins in the cell membrane link hormone receptors to
the second messenger mechanisms. Second messenger mechanisms
include the following:
o Adenylyl cyclase–cyclic adenosine monophosphate (cAMP).
Hormone-receptor interaction may stimulate (or inhibit) the
membrane-bound enzyme adenylyl cyclase. Stimulation of this
enzyme results in synthesis of the second messenger cAMP. The
cAMP activates protein kinase A, leading to phosphorylation that
either activates or inactivates target enzymes.
Plasma membrane phospholipids. Hormone-receptor interaction activates
the membrane-bound enzyme phospholipase C, which in turn causes
phospholipids in the cell membrane (especially those derived from
phosphatidylinositol) to split into the second messengers diacylglycerol and
inositol triphosphate. Inositol triphosphate mobilizes calcium from internal
stores, such as the endoplasmic reticulum, and the calcium in turn
activates protein kinase C. Phosphorylation of enzymes by protein kinase
C activates and deactivates enzymes mediating the hormone responses.
2
, Hormones which use Adenylyl Cyclase-cAMP
second messenger system
An enzyme-linked receptor-the leptin receptor. The
receptor exists as a homodimer (two identical
parts), and leptin binds to the extracellular part of
the receptor, causing phosphorylation and
activation of the intracellular associated janus
kinase 2 (JAK2). This causes phosphorylation of
signal transducer and activator of transcription
(STAT) proteins, which then activates the
transcription of target genes and the synthesis of
proteins. JAK2 phosphorylation also activates
several other enzyme systems that mediate some
of the more rapid effects of leptin.
In addition, the activity of protein kinase C is further enhanced by the second messenger diacylglycerol. Finally, diacylglycerol is
hydrolysed to arachidonic acid, which is the precursor for prostaglandins, which also influence hormonal responses.
o Calcium-calmodulin. Hormone-receptor interaction activates calcium channels in the plasma membrane, permitting
calcium to enter cells. Calcium may also be mobilized from intercellular stores such as the endoplasmic reticulum. The
calcium ions bind with the protein calmodulin, and this complex alters the activity of calcium-dependent enzymes and thus
intercellular reactions.
Protein/peptide hormones may exert actions independent of G-protein-linked second messenger events, and other second
messenger mechanisms may transduce hormonal responses. For example, the second messenger cyclic GMP mediates the
effects of atrial natriuretic peptide. Furthermore, in the case of the peptide hormone insulin, hormone binding to the cell surface
receptor results in phosphorylation of an intracellular site of the receptor, which in turn alters enzymatic activity by phosphorylating
(or dephosphorylating) other proteins in the cell.
Cell Responses to Steroid and Thyroid Hormones Are Mediated
by Stimulating Protein Synthesis.
In contrast to protein/peptide hormones and catecholamines,
steroid and thyroid hormones enter the cell and bind to
intracellular receptors located in the cytoplasm or nucleus of the
cell. The hormone-receptor interaction results in a conformational
change in the receptor. This permits binding of the hormone-
receptor complex to specific points on DNA strands in the
chromosomes; which results in activation of specific genes,
transcription, and translation of proteins that are essential for
mediating the hormonal response. Because the transcription
mechanism is involved in mediating the hormonal response, hours
may be required for the biologic effects to become evident
3
62. General principles of hormonal regulation. Chemistry of hormones. Storage and secretion of hormones.
Mechanisms of hormonal action.
63. Function of the anterior pituitary gland. Control of pituitary secretion by the hypothalamus.
Physiological functions of growth hormone.
64. The posterior pituitary gland and its relation to the hypothalamus.
Physiological function of antidiuretic hormone and oxytocin.
65. The thyroid gland. Functions of the thyroid metabolic hormones.
Regulation of thyroid hormone secretion.
66. Parathyroid hormone, Calcitonin, calcium and phosphate metabolism.
67. Endocrine function of the pancreas. Insulin and its metabolic effects.
Glucagon and its functions. Regulation of the blood glucose concentration.
68. The adrenal glands. Functions of the mineralocorticoids.
69. The adrenal glands. Functions of the glucocorticoids.
70. Adrenal androgens. Abnormalities of adrenocortical secretion. The prostaglandins.
71. Reproductive and hormonal function of the male. Functions of testosterone.
Control of male sexual functions by hypothalamus and anterior pituitary gland.
72. Female physiology before pregnancy. The monthly ovarian cycle and function of the gonadotropic
hormones. Functions of the ovarian hormones. The monthly endometrial cycle and menstruation.
Interplay between the ovarian and hypothalamic - pituitary hormones.
62. GENERAL PRINCIPLES OF HORMONAL REGULATION. CHEMISTRY OF HORMONES.
STORAGE AND SECRETION OF HORMONES. MECHANISM OF HORMONAL ACTION.
General principles of hormonal regulation. The activities of cells, tissues and organs of
the body are coordinated by the interplay of several types of chemical messengers.
o Neural: neurotransmitters are released at synaptic junctions and act locally
o Endocrine: hormones released from specialized glands or cells reach the
circulating blood and influence the function of target cells some distance
away
o Neuroendocrine (neurocrine): secretion products from neurons
(neurohormones) reach the circulating blood and influence the function of
target cells some distance
o Paracrine: cell secretion products diffuse into the extracellular fluid and
affect neighbouring target cells
o Autocrine: cell secretion products affect the function of the same cell by
binding to cell surface receptors
o Cytokine: secreted cell proteins function as autocrines, paracrines, or
endocrines and often act on a broad spectrum of target cells.
Chemistry of hormones.
Chemically, hormones and neurohormones are of three types:
Proteins and peptides. Included in this group are peptides ranging from as small as three amino acids (thyrotropin-releasing
hormone) to proteins almost 200 amino acids long (growth hormone and prolactin).
Steroids. These are derivatives of cholesterol and include the adrenocortical (cortisol, aldosterone) and gonadal (testosterone,
estrogen, progesterone) hormones.
Derivatives of the amino acid tyrosine. Included in this group are hormones from the thyroid gland (thyroxine, triiodothyronine)
and adrenal medulla (epinephrine and norepinephrine).
Storage and secretion of hormones.
Protein/peptide hormones are synthesized on the rough endoplasmic reticulum in the same fashion as most other proteins.
o Initial protein formed by the endoplasmic reticulum is larger than the active hormone and is called a preprohormone.
o Signal sequence of this large protein is cleaved in the endoplasmic reticulum to form a prohormone.
o In the Golgi apparatus the prohormone is packaged in secretion granules along with proteolytic enzymes that cleave the
prohormone into active hormone and other fragments.
1
, o When the endocrine cell is stimulated, the secretion granules migrate from the cytoplasm to the cell membrane. Free
hormone and co-peptides are then released into the extracellular fluid by exocytosis.
Steroid Hormones are synthesized from Cholesterol. In contrast to protein/peptide hormones, there is little hormone storage in
steroid-producing endocrine cells.
o There are large stores of cholesterol esters in cytoplasmic vacuoles that can be rapidly mobilized for synthesis of steroid
hormones after stimulation of the steroid-producing cell.
o Once the steroid hormone appears in the cytoplasm, storage does not take place, and the hormone diffuses through the
cell membrane into the extracellular fluid.
o Much of the cholesterol in steroid-producing cells is removed from the plasma, but there is also de novo synthesis of
cholesterol from acetate.
Thyroid Hormones and Catecholamines are synthesised from Tyrosine.
o As with steroid hormones, there is no storage of thyroid hormones in discrete granules, and once thyroid hormones
appear in the cytoplasm of the cell they leave the cell via diffusion through the cell membrane.
o In contrast to steroid hormones, there are large stores of thyroxine and triiodothyronine as part of a large iodinated protein
(thyroglobulin) that is stored in the lumens of thyroid follicles.
o In comparison, the other group of hormones derived from tyrosine, the adrenal medullary hormones epinephrine and
norepinephrine, are taken up into preformed vesicles and stored until secreted.
o As with protein hormones stored in secretion granules, catecholamines are released from adrenal medullary cells through
exocytosis.
Mechanism of hormonal action.
Hormonal Receptors and their activation hormones control cellular processes by interacting with receptors on target cells. These
receptors are (1) either on or within the cell membrane, as in the case of peptide/protein and catecholamine hormones, and (2)
within the cell, in either the cytoplasm or nucleus, as is the case for steroid and thyroid hormones. Receptors are usually specific
for a single hormone. The hormone-receptor interaction is coupled to a signal generating mechanism that then causes a change in
intracellular processes by altering the activity or concentration of enzymes, carrier proteins, and so forth.
In the case of peptide/protein and catecholamine hormones that do not readily pass the cell membrane, interaction with the
receptor on or within the cell membrane often results in generation of a second messenger, which in turn mediates the hormonal
response.
Often, coupling G-proteins in the cell membrane link hormone receptors to
the second messenger mechanisms. Second messenger mechanisms
include the following:
o Adenylyl cyclase–cyclic adenosine monophosphate (cAMP).
Hormone-receptor interaction may stimulate (or inhibit) the
membrane-bound enzyme adenylyl cyclase. Stimulation of this
enzyme results in synthesis of the second messenger cAMP. The
cAMP activates protein kinase A, leading to phosphorylation that
either activates or inactivates target enzymes.
Plasma membrane phospholipids. Hormone-receptor interaction activates
the membrane-bound enzyme phospholipase C, which in turn causes
phospholipids in the cell membrane (especially those derived from
phosphatidylinositol) to split into the second messengers diacylglycerol and
inositol triphosphate. Inositol triphosphate mobilizes calcium from internal
stores, such as the endoplasmic reticulum, and the calcium in turn
activates protein kinase C. Phosphorylation of enzymes by protein kinase
C activates and deactivates enzymes mediating the hormone responses.
2
, Hormones which use Adenylyl Cyclase-cAMP
second messenger system
An enzyme-linked receptor-the leptin receptor. The
receptor exists as a homodimer (two identical
parts), and leptin binds to the extracellular part of
the receptor, causing phosphorylation and
activation of the intracellular associated janus
kinase 2 (JAK2). This causes phosphorylation of
signal transducer and activator of transcription
(STAT) proteins, which then activates the
transcription of target genes and the synthesis of
proteins. JAK2 phosphorylation also activates
several other enzyme systems that mediate some
of the more rapid effects of leptin.
In addition, the activity of protein kinase C is further enhanced by the second messenger diacylglycerol. Finally, diacylglycerol is
hydrolysed to arachidonic acid, which is the precursor for prostaglandins, which also influence hormonal responses.
o Calcium-calmodulin. Hormone-receptor interaction activates calcium channels in the plasma membrane, permitting
calcium to enter cells. Calcium may also be mobilized from intercellular stores such as the endoplasmic reticulum. The
calcium ions bind with the protein calmodulin, and this complex alters the activity of calcium-dependent enzymes and thus
intercellular reactions.
Protein/peptide hormones may exert actions independent of G-protein-linked second messenger events, and other second
messenger mechanisms may transduce hormonal responses. For example, the second messenger cyclic GMP mediates the
effects of atrial natriuretic peptide. Furthermore, in the case of the peptide hormone insulin, hormone binding to the cell surface
receptor results in phosphorylation of an intracellular site of the receptor, which in turn alters enzymatic activity by phosphorylating
(or dephosphorylating) other proteins in the cell.
Cell Responses to Steroid and Thyroid Hormones Are Mediated
by Stimulating Protein Synthesis.
In contrast to protein/peptide hormones and catecholamines,
steroid and thyroid hormones enter the cell and bind to
intracellular receptors located in the cytoplasm or nucleus of the
cell. The hormone-receptor interaction results in a conformational
change in the receptor. This permits binding of the hormone-
receptor complex to specific points on DNA strands in the
chromosomes; which results in activation of specific genes,
transcription, and translation of proteins that are essential for
mediating the hormonal response. Because the transcription
mechanism is involved in mediating the hormonal response, hours
may be required for the biologic effects to become evident
3
