Etando Ayuk (MSc.

Chemical pathology) 24/06/2020

Ml 105
Unit 8
Biochemistry
of Hormones
Biochemistry of Hormones
INDICATIVE CONTENT

 Definition, Roles, Regulation

 Classify the hormones according to their chemical structure.
 mechanisms action of hormones.
 Regulation of Hormones
 transport of hormones
 Metabolism of hormones
 Discuss Clearance of hormones from blood.

Recommended Readings
Essentials of Medical Biochemistry
With Clinical Cases
2nd Edition,
N. V. Bhagavan Chung-Eun Ha
[Chapter 28],

Clinical Chemistry Techniques, Principles, Correlations

6th Edition
Michael L. Bishop, Edward P. Fody , Larry E. Schoeff]
210
[Chapter 19]

Ml 105
Unit 7
Biochemistry
of Hormones
Biochemistry of Hormones
Background and Introduction to Hormones
 The term hormone (hormao G = to excite) was first used by William M. Bayliss and his brother-in-law
Ernest H.Starling, both of London University College, in 1904, who showed that a chemical substance
(secretin) from the intestine could stimulate the action of a pancreatic secretion.

 These substances were then called as ‘chemical messengers’ . Went and Thimann (1937) defined a
hormone as “a substance which, produced in any one part of an organism, is transferred to another part
and there influences a specific physiological process. ”

 The tissues or organs where they are produced are called as effectors and those where they exert their
influence as targets.

 These have low molecular weight and diffuse readily . As they are readily oxidized, their effects do not
remain permanent unless these are supplied continuously

 Hormones are biologically active substances which are released into the blood by the endocrine glands
and humoral way (though blood, lymph, saliva, cerebrospinal fluid) to regulate and physiological
processes
211
 Hormones secretion can be Endocrine hormones or Neuroendocrine hormones
Etando Ayuk (MSc. Chemical pathology) 24/06/2020

Ml 105
Unit 7
Biochemistry
of Hormones
Biochemistry of Hormones
Background and Introduction to Hormones
 Based on their site on action, the hormones are of two types : local and general. The local hormones,
obviously, have specific local effects, whence their nomenclature.

 These may be exemplified by acetylcholine, secretin, cholecystokinin etc. The general hormones, on the
other hand, are secreted by specific endocrine glands and are transported in the blood to cause
physiologic actions at points remote from their place of origin.

 A few of the general hormones affect almost all cells of the body, e.g., growth hormones (GH) and
thyroid hormones ; whereas other general hormones, however, affect specific tissues far more than other
tissues, e.g ., adrenocorticotropin (a hormone secreted from adenohyprophysis and stimulating the
adrenal cortex) and ovarian hormones (affecting the uterine endometrium).

 Endocrine hormones are released by glands or specialized cells into the circulating blood & influence the
function of target cells at another location in the body.

 Neuroendocrine hormones are secreted by neurons into the circulating blood & influence the function of
target cells at another location in the body.`
Function: To integrate with Neural system of body & thus maintain the homeostasis of the body.
212

Ml 105
Unit 7
Biochemistry
of Hormones
Biochemistry of Hormones
Body activity is coordinated by various chemical messenger systems
 Neurotransmitters: Released by axon terminals of neurons into the synaptic junctions
 Act locally to control nerve cell functions Eg: ACh, GABA.
 Endocrine hormones
 Released by glands or specialized cells into the circulating blood
 Influence the function of cells at another location in the body
 Eg: Insulin, Epinephrine
 Neuroendocrine hormones
 Secreted by neurons into the circulating blood
 Influence the function of cells at another location in the body
 Eg: Oxytocin, ADH
 Paracrines ((local mediator)
 They are secreted by cells into the extracellular fluid and affect
neighboring target cells of a different type.
 Eg: IL-1 from macrophages that stimulates the bound T cell to
proliferate and differentiate
 Autocrines:
 They are secreted by cells into the extracellular fluid and affect the
function of the same cells that produced them.
 Eg: Autostimulatory release of IL-2 enhances the response of a T cell to
IL-1 213
Etando Ayuk (MSc. Chemical pathology) 24/06/2020

Ml 105
Unit 7
Biochemistry
of Hormones
Endocrine glands and hormones:
Body activity is co-ordinated by various chemical messenger systems
 Neurotransmitters: Released by axon terminals of neurons into the synaptic junctions
 Act locally to control nerve cell functions
 Eg: ACh, GABA.
 Endocrine hormones
 Released by glands or specialized cells into the circulating blood
 Influence the function of cells at another location in the body
 Eg: Insulin, Epinephrine
 Neuroendocrine hormones
 Secreted by neurons into the circulating blood
 Influence the function of cells at another location in the body
 Eg: Oxytocin, ADH
 Paracrines ((local mediator) Eg: IL-1 from macrophages
 that stimulates the bound T cell to proliferate and differentiate
 Autokines
 Eg: Autostimulatory release
 of IL-2 enhances the
 response of a T cell to IL-1
214

Ml 105
Unit 7
Biochemistry
Characteristics of the Endocrine System
of Hormones

 Composed of glands that secrete hormones into the circulatory system.

 Hormones are secreted in minute amounts into the interstitial space.
 Hormones eventually enter the circulatory system and arrive at specific target tissues.

Functions are similar to the nervous system.

Differences;
Amplitude-modulated vs. Frequency-modulated
Response of target tissue to hormones is usually slower and of longer duration than that to neurons.

Functions of Hormones
 Maintenance of growth & development – Growth hormone, Thyroxine, insulin, Glucocorticoid, &
Gonadal hormones
 Maintenance of internal environment – ADH, Mineralocorticoids, PTH
 Regulation of energy balance and metabolism –Insulin, glucagon , Leptin & Ghrelin
 Reproduction & species propagation – Gonadal & Pituitary hormones
215
Etando Ayuk (MSc. Chemical pathology) 24/06/2020

Ml 105
Unit 7
Biochemistry
of Hormones
Chemical Messenger Systems
Body activity is co-ordinated by various chemical messenger systems
 Neurotransmitters: Released by axon terminals of neurons into the synaptic junctions
 Act locally to control nerve cell functions
 Eg: ACh, GABA.
 Endocrine hormones
 Released by glands or specialized cells into the circulating blood
 Influence the function of cells at another location in the body
 Eg: Insulin, Epinephrine
 Neuroendocrine hormones
 Secreted by neurons into the circulating blood
 Influence the function of cells at another location in the body
 Eg: Oxytocin, ADH
 Paracrines ((local mediator) Eg: IL-1 from macrophages
 that stimulates the bound T cell to proliferate and differentiate
 Autokines
 Eg: Autostimulatory release
 of IL-2 enhances the
 response of a T cell to IL-1
216

Ml 105
Unit 7
Biochemistry
Chemical Structure of Hormones
of Hormones

Hormones can be largely grouped based on chemical nature into the following;
 Peptides & Proteins:
 Most hormones are either peptides or proteins and are usually referred to as peptide hormones.
 Hormones secreted by anterior and posterior pituitary gland
 Example: Insulin and glucagon, Parathyroid hormone

 Amines
 Amine hormones are derivatives of the amino acid tyrosine.
 Thyroid (thyroxine and triiodothyronine)
 Adrenal medullae (epinephrine and norepinephrine)
 Dopamine [Prolactin Inhibiting Factor]

 Lipids & Steroids: Steroid hormones are produced by the adrenal cortex and the gonads.
 Adrenal cortex (cortisol and aldosterone)
 Ovaries (estrogen and progesterone)
 Testes (testosterone)
 Placenta (estrogen and progesterone)

 There are no known polysaccharides or nucleic acid hormones

217
Etando Ayuk (MSc. Chemical pathology) 24/06/2020

Ml 105
Unit 7
Biochemistry
Chemical Structure of Hormones
of Hormones

Hormones can be largely grouped based on chemical nature into the following;
 Peptides & Proteins:
 Most hormones are either peptides or proteins and are usually referred to as peptide hormones.
 Hormones secreted by anterior and posterior pituitary gland
 Example: Insulin and glucagon, Parathyroid hormone

 Amines
 Amine hormones are derivatives of the amino acid tyrosine.
 Thyroid (thyroxine and triiodothyronine)
 Adrenal medullae (epinephrine and norepinephrine)
 Dopamine [Prolactin Inhibiting Factor]

 Lipids & Steroids: Steroid hormones are produced by the adrenal cortex and the gonads.
 Adrenal cortex (cortisol and aldosterone)
 Ovaries (estrogen and progesterone)
 Testes (testosterone)
 Placenta (estrogen and progesterone)

 There are no known polysaccharides or nucleic acid hormones

218

Ml 105
Unit 7
Biochemistry
Hormone secretion
of Hormones
 Hormones in animals are often transported in the blood. Endocrine hormone molecules are secreted
(released) directly into the bloodstream, while exocrine hormones (ecto-hormones) are secreted directly
into a duct, and from the duct they either flow into the bloodstream or they flow from cell to cell by
diffusion
 Hormone secretion can be stimulated and inhibited by:
 Other hormones (stimulating or releasing hormones)
 Plasma concentrations of ions or nutrients
 Neurons and mental activity
 Environmental changes, E.g. Change in light or temperature

Control of Hormone Secretion:

Control of secretion is in the form of neural, hormonal, or humoral stimuli.
1. NEURAL: The adrenal medulla is directly stimulated by the sympathetic nervous system. Epinephrine and NE
reinforce the actions of the sympathetic nervous system.

2. HORMONAL: Occurs when hormones from one endocrine gland stimulate the secretion of hormones from another
endocrine gland. E.g. TRHTSH TH E.g. CRH ACTH Cortisol These routes of secretion are usually controlled in a negative
feedback manner.
3. HUMORAL: Occurs when substances other than hormones control the secretion of endocrine glands. E.g. Insulin
secretion by the pancreas is determined by several factors. Rise in glucose after a meal triggers insulin secretion. Rise
in amino acids after a meal triggers insulin secretion. In addition hormonal and neural stimuli also play a role in
219
insulin secretion.
Etando Ayuk (MSc. Chemical pathology) 24/06/2020

Ml 105
Unit 7
Biochemistry
MECHANISM OF HORMONE ACTION?
of Hormones

 Hormones activate target cells by diffusing through the plasma membrane of the target cells (lipid-
soluble hormones) to bind a receptor protein within the cytoplasm of the cell, or by binding a specific
receptor protein in the cell membrane of the target cell (water-soluble proteins). In both cases, the
hormone complex will activate a chain of molecular events within the cell that will result in the
activation of various processes

 Hormones act by binding to receptor molecules, the binding hormone changes the shape of the
receptor causing the response of the hormones.
 These mechanism can be classified into
 Non – Steroid Hormones or hormones with cell surface receptors or
 Steroid hormones or hormones with intracellular receptors

FACTORS REGULATING HORMONE ACTION

 Action of a hormone at a target organ is regulated by four factors:

 Rate of synthesis and secretion: The hormone is stored in the endocrine glands.
 In some cases, specific transport systems in plasma.
 Hormone-specific receptors in target cell membranes which differ from tissue to tissue.
 Ultimate degradation of the hormones usually by the liver or kidneys. 220

Ml 105
Unit 7 Control of Hormone Secretion Rates
Biochemistry
of Hormones Negative Feedback mechanism
 Hormones control the rates of many
activities in the body.

 The rate at which each hormone is secreted

is controlled by a negative feedback
mechanism.

 Three major patterns of regulation:

 Non-hormone substance (e.g. insulin)
 Stimulation by the nervous system (e.g.
epinephrine)
 Hormone from another endocrine tissue
(e.g. TRH, TSH)
FEEDBACK CONTROL OF HORMONE SECRETION

 Negative Feedback Prevents Overactivity of

Hormone Systems

 Surges of Hormones Can Occur With Positive

221
Feedback.
Etando Ayuk (MSc. Chemical pathology) 24/06/2020

Ml 105
Unit 7 Control of Hormone Secretion Rates
Biochemistry
of Hormones Negative and Positive Feedback mechanism

 Hormones control the rates of many activities in the body.

 The rate at which each hormone is secreted is controlled by a negative feedback mechanism.
 Three major patterns of regulation:
 Non-hormone substance (e.g. insulin)
 Stimulation by the nervous system (e.g. epinephrine)
 Hormone from another endocrine tissue (e.g. TRH, TSH)
FEEDBACK CONTROL OF HORMONE SECRETION
Negative Feedback Prevents Overactivity of Hormone Systems Surges of Hormones Can Occur With Positive
Feedback.

222

Ml 105
Unit 7
Biochemistry
TRANSPORT OF HORMONES IN THE BLOOD
of Hormones

 Hormones are dissolved in the blood plasma and transported in free form or bound to a protein carrier
 As a result, hormones can be distributed throughout the body relatively quickly.

 Hormones diffuse from the capillary to the interstitial space.

 Lipid-soluble hormones diffuse through the walls of all capillaries.
 Water-soluble hormones must pass through pores.

 Water-soluble hormones (peptides and catecholamines)

 Dissolved in the plasma and transported to target tissues, where they diffuse out of the
capillaries, into the interstitial fluid and to target cells.
 Steroid and thyroid hormones
 Circulate in the blood as mainly bound to plasma proteins.
 Usually less than 10 per cent of steroid or thyroid hormones in
the plasma exist free in solution.
 Protein-bound hormones cannot easily diffuse across the
capillaries
 Hence, biologically inactive until they dissociate from plasma
proteins
 Bound forms act as a reservoir. 223
Etando Ayuk (MSc. Chemical pathology) 24/06/2020

Ml 105
Unit 7
Biochemistry
HORMONE Metabolism and Excretion
of Hormones

 Water-soluble hormones have relatively short half-lives because they are rapidly broken down by
enzymes.
 These hormones normally have concentrations that increase and decrease rapidly in the blood.
 They generally regulate activities that have a quick onset and a short duration.

 Lipid-soluble hormones are usually bound to protein carriers.

 The rate at which these hormones are broken down is greatly reduced.
 Therefore, these hormones have longer half-lives.

 Hormones are removed from the blood in four ways.

 Excretion (kidney, liver)
 Metabolism (enzymes)
 Active transport (actively transported into cells and secreted again)
 Conjugation (attach water-soluble molecules to hormone and then excreted by kidney or liver).

224

Ml 105
Unit 7
Factors that increase / decrease the
Biochemistry
of Hormones
concentration of a hormone in the blood.

1. Rate of hormone secretion into the blood. &

2. Rate of removal of the hormone from the blood.
 Metabolic clearance rate =Rate of disappearance of hormone from the plasma/Concentration of
hormone .
 Expressed : Number of ml of plasma cleared of the hormone/ minute.

225
Etando Ayuk (MSc. Chemical pathology) 24/06/2020

Ml 105
Unit 7
Biochemistry
of Hormones
REVIEW QUESTIONS

1. Define a Hormone
2. Classify the hormones according to
1. Chemical nature
2. Based on their site of action
3. Differentiate between the following
1. Endocrine hormones and Neuroendocrine hormones
2. Paracrine and Autocrine Hormones
3. Neurotransmitters and Neuroendocrine hormones
4. Outline four functions of hormones.
5. The Control of secretion of hormones can take the form of neural, hormonal, or humoral stimuli
controls. Explain the underlined words as related to the statement.
6. Explain the mechanism of hormonal action and state two factors that can regulate hormonal action
7. What do you understand by the Negative Feedback mechanism of hormonal regulation?
8. Explain how Water-soluble hormones and non -Water-soluble hormones are transported.
9. Discuss Clearance of hormones from blood.

226