Principles of Biochemistry, Volume 3 - A. Lehninger 1985

Selected Aspects of Human Biochemistry
Hormones
Some General Properties of Hormones

Several generalisations can be made regarding the Structure and function of Hormones.

a. There are three classes of hormones: peptide, steroid, and amine.

Peptide Hormones (Table 25-1), which may contain anywhere from 3 to 200 amino acid residues, include all Hypothalamic and pituitary hormones, as well as Insulin and Glucagon secreted by the Pancreas.

Class="center">Table 25-1. Major Classes of hormones and their representatives

Hormones belonging to the amine class are low-molecular-weight, Water-soluble compounds containing amino groups; these include epinephrine, secreted by The adrenal medulla, and THYROID HORMONES. Steroid hormones (which are highly lipid-soluble) include Adrenocortical Hormones, androgens (Male Sex Hormones), and estrogens (Female Sex Hormones).

b. Some polypeptide hormones are formed from inactive precursors.

Certain polypeptide hormones, including insulin and glucagon, are initially synthesised in endocrine Cells as inactive precursors known as prohormones. These inactive precursors have longer polypeptide chains than their corresponding active hormones. A case in point is proinsulin (whose polypeptide chain contains approximately 80 amino acid residues), which is converted into active insulin (containing 51 amino acid residues) through the Enzymatic Cleavage of a portion of the polypeptide chain. Prohormones are stored in an inactive form within the endocrine Cell, typically in its secretory granules. Upon receiving an appropriate signal, The Cell can rapidly convert the prohormone into the active hormone via enzymatic action.

c. Hormones act at very low concentrations and in most cases have a short half-life.

The basal (unstimulated) hormone level in the Blood is extremely low, ranging from micromolar (10^-6 M) to picomolar (10^-12 M) concentrations. In this respect, hormones differ sharply from, for example, glucose, which is present in the blood at millimolar concentrations (approximately 4∙10^-3 M). Because of their low concentration, hormones are extremely difficult to isolate, identify, and accurately quantify. The exceptionally high sensitivity of the radioimmunoassay method described below has opened up entirely new research possibilities in hormone biochemistry, enabling the quantitative measurement of many hormones at minute concentrations.

When the secretion of a given hormone is stimulated, its blood concentration sometimes increases by several orders of magnitude. Once secretion ceases, the hormone concentration rapidly returns to baseline. The lifespan of hormones in the blood is very short, often not exceeding a few minutes. As soon as the presence of a hormone is no longer required, it is rapidly inactivated by Enzymes.

d. Some hormones act rapidly, others slowly.

Certain hormones provoke an immediate biochemical or physiological response. For instance, the Liver begins releasing glucose into the bloodstream within seconds of epinephrine being discharged into Circulation. Conversely, in the case of thyroid hormones or estrogens, the response of target Tissues reaches its peak over the course of several hours or even days. As we shall see, these differences in response time correspond to differences in the Mechanisms of Hormone action.

e. Hormones bind to specific receptors located either On the surface or inside the target cell.

The initial step in the action of any hormone is its binding to a specific molecule or group of molecules known as a hormone receptor, which is typically localised either on The surface of the target cell or in the Cytosol. The receptor exhibits exceptionally high Specificity and affinity for its corresponding hormone. The receptors for water-soluble peptide and amine hormones, which cannot readily cross The cell membrane, are located on the outer surface of target cells, whereas the specific Proteins that serve as receptors for lipid-soluble steroid hormones—which easily penetrate the membrane—are localised in the cytosol of target cells.

f. Hormone action can be mediated through intracellular second messengers.

Once a hormone molecule binds to a receptor on the surface or inside a target cell, the receptor undergoes characteristic conformational changes that lead to the generation or release within the cell of a mediator commonly referred to as a second messenger. This messenger relays the signal from the hormone receptor to the appropriate enzyme or molecular system within the cell that actually executes the command delivered by the hormone. The intracellular messenger either regulates The rate of a specific enzymatic reaction or turns on the expression of a Gene (or group of genes) that was previously inactive.