Biochemistry and Human Nutrition

Module 4. Human nutrition

Lesson 28
HORMONES

28.1 Introduction

• The living body possesses a remarkable communication system to coordinate its biological functions. This is achieved by two distinctly organized functional systems.

• The nervous system coordinates the body functions through the transmission of electrochemical impulses.
• The endocrine system acts through a wide range of chemical messengers known as hormones.

• Hormones are the chemical messengers of the body having diverse structures and functions. They act either directly or through messengers to coordinate and perform biological functions such as growth, reproduction and digestion etc.
• Hormones are defined as organic substances, produced in small amounts by specific tissues (endocrine glands), secreted into the blood stream to control the metabolic and biological activities in the target cells.
• Hormones may be regarded as the chemical messengers involved in the transmission of information from one tissue to another and from cell to cell. The major endocrine organs in human body are depicted in fig 28.1.

Fig. 28.1 Location of endocrine glands

28.2 Classification of Hormones

• Based on the chemical nature the hormones can be categorized into three groups

1. Protein or peptide hormones e.g. insulin, glucagon, antidiuretic hormone, oxytocin.
2. Steroid hormones e.g. glucocorticoids, mineralocorticoids, sex hormones.
3. Amino acid derivatives e.g. epinephrine, norepinephrine, thyroxine (T4), triiodothyronine (T3).

• Based on the mechanism of action

Hormones are classified into two broad groups (I and II) based on the location of the receptors to which they bind and the signals used to mediate their action.

• Group I hormones: These hormones bind to intracellular receptors to form receptor-hormone complexes (the intracellular messengers) through which their biochemical functions are mediated. Group I hormones are lipophilic in nature and are mostly derivatives of cholesterol (exception – T3 and T4). e.g. estrogens, androgens, glucocorticoids, calcitriol.
• Group II hormones: These hormones bind to cell surface (plasma membrane) receptors and stimulate the release of certain molecules, namely the second messengers which, in turn, perform the biochemical functions. Thus, hormones themselves are the first messengers.
• Group II hormones are subdivided into three categories based on the chemical nature of the second messengers.

• The second messenger is cAMP e.g. ACTH, FSH, LH, PTH, glucagon, calcitonin.
• The second messenger is phosphatidylinositol/calcium e.g. TRH, GnRH, gastrin, CCK.
• The second messenger is unknown e.g. growth hormone, insulin, oxytocin, prolactin.

The principal human hormones, their classification based on the mechanism of action, and major functions are given in Table- 28.1

28.3 Mechanism of action

• Group I hormones

These hormones are lipophilic in nature and can easily pass across the plasma membrane. They act through the intracellular receptors located either in the cytosol or the nucleus. The hormone-receptor complex binds to specific regions on the DNA called hormone responsive element (HRE) and causes increased expression of specific genes (Fig-28.2). It is believed that the interaction of hormone receptor complex with HRE promotes initiation and, to a lesser extent, elongation and termination of RNA synthesis (transcription). The ultimate outcome is the production of specific proteins (translation) in response to hormonal action.

Fig. 28.2 Mechanism of action of intracellular receptor hormones

• Group II hormones

These hormones are considered as the first messengers. They exert their action through mediatory molecules, collectively called second messengers. Cyclic AMP (cAMP) is a ubiquitous nucleotide. It consists of adenine, ribose and a phosphate. cAMP acts as a second messenger for a majority of polypeptide hormones. The membrane-bound enzyme adenylate cyclase converts ATP to cyclic AMP. cAMP is hydrolysed by phosphodiesterase Fig-28.3 and 28.4.

• Adenylate cyclase system

A series of events occur at the membrane level that influence the activity of adenylate cyclase leading to the synthesis of cAMP. This process is mediated by G-proteins, so designed due to their ability to bind to guanine nucleotides.

• Action of cAMP – a general view

Once produced, cAMP performs its role as a second messenger in eliciting biochemical responses. cAMP activates protein kinase A (PKA). This enzyme is a hetrotetramer consisting of 2 regulatory subunits (R) and 2 catalytic subunits (C). cAMP binds to inactive protein kinase and causes the dissociation of R and C subunits. (Fig-28.4)

4cAMP + R₂C₂→ R₂(4cAMP) + 2C

(interactive) (interactive) (active)

The active submit (C) catalyses phosphorylation of proteins (transfer of phosphate group to serine and threonine residues). It is the phosphoprotein that ultimately causes the biochemical response.

It should, however, be remembered that cAMP does not act on all protein kinases. For instance, on protein kinase C (the second messenger is diacylglycerol).

Fig. 28.3 cAMP – The second messenger

• Dephosphorylation of proteins: A group of enzymes called protein phosphatases hydrolyse and remove the phosphate group added to proteins.

Fig. 28.4 Mechanism of action of cell surface receptor hormones

Table-28.1 Principal human hormones – classification (by mechanism of action), origin and major functions