Technical Discussion

Nature uses a diverse spectrum of molecules as hormones, and knowing the basic structure of a hormone imparts considerable knowledge about its receptor and mechanism of action. Additionally, the simpler structures can often be exploited to generate similar molecules - agonists and antagonists - that are therapeutically valuable.

Like all molecules, hormones are synthesized, exist in a biologically active state for a time, and then degrade or are destroyed. Having an appreciation for the "half-life" and mode of elimination of a hormone aids in understanding its role in physiology and is critical when using hormones as drugs.

Most commonly, hormones are categorized into four structural groups, with members of each group having many properties in common:

• Peptides and proteins

• Steroids

• Amino acid derivatives

• Fatty acid derivatives - Eicosanoids

Lay Interpretation

An amazing array of substances are used by the body as hormones.

Hormones do not persist in the body.  The duration of hormones in the body differs from seconds to hours, depending on the hormone in question. 

An overview of the half-life and the way they are used and eliminated is useful when exploring the deeper aspects of endocrinology.

There are four structural groups of hormones.  Many substances in each specific group share common aspects and characteristics.

Peptide and protein hormones are, of course, products of translation. They vary considerably in size and post-translational modifications, ranging from peptides as short as three amino acids to large, multi-subunit glycoproteins.

Many protein hormones are synthesized as pro-hormones, then proteolytically clipped to generate their mature form. In other cases, the hormone is originally embedded within the sequence of a larger precursor, then released by multiple proteolytic cleavages.

Peptide hormones are synthesized in endoplasmic reticulum, transferred to the Golgi and packaged into secretory vesicles for export. They can be secreted by one of two pathways:

• Regulated secretion: The cell stores hormone in secretory granules and releases them in "bursts" when stimulated. This is the most commonly used pathway and allows cells to secrete a large amount of hormone over a short period of time.

• Constitutive secretion: The cell does not store hormone, but secretes it from secretory vesicles as it is synthesized.

Most peptide hormones circulate unbound to other proteins, but exceptions exist; for example, insulin-like growth factor-1 binds to one of several binding proteins. In general, the halflife of circulating peptide hormones is only a few minutes.

Peptide and protein hormones vary greatly in size and many will vary during their life cycle as they are used and reacted with in the body.

Peptides are arrangements of amino acids (protein chains) and may be as short as three aminos right up to massive and complex multi-tiered monsters.

Peptides hormones are most commonly made and stored for bursts of secretion but some are secreted as soon as they are made.

Peptide hormones (like hGH) are very short lived in the body, commonly having a half-life lasting only minutes.

Steroids are lipids and, more specifically, derivatives of cholesterol. Examples include the sex steroids such as testosterone and adrenal steroids such as cortisol.

The first and rate-limiting step in the synthesis of all steroid hormones is conversion of cholesterol to pregnenolone, which is illustrated here to demonstrate the system of numbering rings and carbons for identification of different steroid hormones.

Pregnenolone is formed on the inner membrane of mitochondria then shuttled back and forth between mitochondrion and the endoplasmic reticulum for further enzymatic transformations involved in synthesis of derivative steroid hormones.

Newly synthesized steroid hormones are rapidly secreted from the cell, with little if any storage. Increases in secretion reflect accelerated rates of synthesis. Following secretion, all steroids bind to some extent to plasma proteins.

This binding is often low affinity and non-specific (e.g. to albumin), but some steroids are transported by specific binding proteins, which clearly affects their half-life and rate of elimination.

Steroid hormones are typically eliminated by inactivating metabolic transformations and excretion in urine or bile.

Lipid hormones are all produced from cholesterol and are called steroids.

Sex hormones are a good example of steroid hormones.

Cholesterol is converted to pregnenolone, which is then used as required for further modification into the myriad of steroids used in the body.

Steroids are rapidly secreted as soon as they are made with little if any storage for the most part.

The half-life of steroids vary considerably from quite quick (minutes) to a few hours.

There are two groups of hormones derived from the amino acid tyrosine:

• Thyroid hormones are basically a "double" tyrosine with the critical incorporation of 3 or 4 iodine atoms.

• Catecholamines include epinephrine and norepinephrine, which are used as both hormones and neurotransmitters.

The pathways to synthesis of these hormones is provided in the sections on the thyroid gland and the adrenal medulla.

The circulating half-life of thyroid hormones is on the order of a few days. They are inactivated primarily by intracellular deiodinases.

 Catecholamines, on the other hand, are rapidly degraded, with circulating half-lives of only a few minutes.

Two other amino acids are used for synthesis of hormones:

• Tryptophan is the precursor to serotonin and the pineal hormone melatonin

• Glutamic acid is converted to histamine

Two groups of hormones are derived from a specific amino-acid called Tyrosine.

 Tryptophan and Glutamic acid are also useful in the production of these amino derivative hormones.

The half-life of these hormones is in the order of a few days for the thyroid hormones and minutes for others.

Eicosanoids are a large group of molecules derived from polyunsaturated fatty acids. The principal groups of hormones of this class are prostaglandins, prostacyclins, leukotrienes and thromboxanes.

Arachadonic acid is the most abundant precursor for these hormones. Stores of arachadonic acid are present in membrane lipids and released through the action of various lipases. The specific eicosanoids synthesized by a cell are dictated by the battery of processing enzymes expressed in that cell.

These hormones are rapidly inactivated by being metabolized, and are typically active for only a few seconds.

This last group of fatty acid Eicosanoids are sourced from polyunsaturated fatty acids.

Their half life is measured in seconds and are very complex in their structures.