Introduction to Endocrine Physiology

Endocrine Secretion

The term endocrine means "internal secretion". An endocrine regulatory molecule (hormone) is a substance that is released into the internal environment of the body, in other words, the extracellular fluid (ECF). This is in contrast to exocrine secretions, which are released to the external environment. An example of exocrine secretion is digestive tract secretion. In this case, cells in organs such as the stomach, pancreas, and small intestine secrete substances such as digestive enzymes that wind up in the lumen of the digestive tract. Because the lumen of the digestive tract is continuous with the external environment, this is exocrine secretion.

You should note that the term secretion is used in a somewhat different sense in endocrinology. In cell biology, secretion refers specifically to transport across the cell membrane.  For a typical polar hormone, secretion is achieved by exocytosis of secretory vesicles. In endocrinology, secretion refers to whatever occurs to increase the amount of hormone in the circulation. This broader definition is useful because many hormones are nonpolar substances whose release into the circulation cannot be regulated by exocytosis.

Chemical Classes of Hormones

It is useful to know the chemical classification of a hormone because there are generalities about the synthesis, secretion, receptor type, and response characteristics that can be made based on the chemical nature of the hormone. The two broad categories are polar hormones and nonpolar hormones.

Polar hormones include the catecholamines and the polypeptide hormones. The catecholamines (dopamine, norepinephrine, and epinephrine) are synthesized in the cytosol through enzymatic modification of the amino acid tyrosine.  A transporter protein is responsible for their delivery into secretory vesicles.

The largest group of hormones are polypeptide hormones (click link to see list).  Polypeptide hormones are synthesized in the rough endoplasmic reticulum (rough ER). Usually, a polypeptide hormone is first synthesized as part of a larger preprohormone. The first step is cleavage of the signal sequence in the rough ER to form a prohormone. (Recall that the signal sequence directs ribosomes synthesizing secreted proteins to dock at the rough ER.) The prohormone is further processed in the Golgi and secretory vesicles to give rise to the active hormone. In some cases, a prohormone may give rise to more than one active hormone. An example is pro-opiomelanocortin (POMC), which gives rise to both adrenocorticotropic hormone (ACTH) and the melanocyte stimulating hormones.

Note that you may see or hear the term "peptide hormone" to refer to all hormones that are polypeptides; this is the convention followed in the Vander textbook. The term "peptide" generally refers to short polypeptides of less than 50 amino acids, while longer polypetides would be referred to as proteins. Most polypeptide hormones are peptides, but some are small proteins.

This figure schematizes the important characteristics about the storage, secretion, and action of the polar hormones. Hormone receptors in the target cell activate signal transduction pathways that alter cellular activity.  Most polar hormones signal via G-protein coupled receptors (seven transmembrane domain proteins).

The nonpolar hormones are the steroid hormones, vitamin D, and thyroid hormones (click link to see list). The steroid hormones and vitamin D are synthesized through chemical modification of cholesterol. Thyroid hormones are initially synthesized as part of a large protein precursor called thyroglobulin. Tyrosine residues within thyroglobulin are iodinated, and then the hormones are released through proteolysis of thyroglobulin.

Because they are lipophilic, nonpolar hormones cannot be stored in secretion vesicles. Instead, hormone secretion is regulated by regulating hormone synthesis. This regulation involves a tropic hormone, usually a peptide hormone, whose binding to a receptor on the endocrine cell regulates hormone synthesis (orange arrows in figure). As hormone is produced, it diffuses across the plasma membrane.

Because they are poorly soluble in plasma, nonpolar hormones in the circulation are found mostly bound to carrier proteins, either albumin, or specific hormone binding proteins. A small amount of hormone exists as free hormone, that is, dissolved in plasma and not bound to binding protein. Free hormone can diffuse across the plasma membrane of target cells. Once inside the cell, nonpolar hormones signal by binding to intracellular receptors (nuclear receptors) that bind to DNA. The hormone-receptor complex acts as a transcription factor, regulating gene expression.

The figure also depicts that nonpolar hormones are often chemically modified by enzymes in target tissues. Sometimes enzyme modification of hormone may inactivate the hormone, but in other instances it may convert the hormone to its active form. For example, the majority of the thyroid hormone produced by the thyroid gland is T4 (3, 5, 3', 5'-tetraiodthyronine or thyroxine), while the form of thyroid hormone that is active in tissues is T3 (3, 5, 3'-triiodothyronine). T4 is converted to T3 in tissues through the action of the enzyme deiodinase.

Quick Quiz

Fill-in Answer Correct False Correct Answer
1. The pancreas secretes the polypeptide hormone insulin, but it also secretes the digestive enzyme trypsin. Which (insulin or trypsin) is considered an exocrine secretion?
2. The secretion of a nonpolar hormone is regulated by regulating __________.
3. Where in the cell are polypeptide hormones synthesized?
4. Name the prohormone from which ACTH and the melanocyte stimulating hormones are produced.
5. Dopamine, epinephrine, and norepinephrine are collectively referred to as the ______________.
6. Which hormone binds to an intracellular receptor, dopamine or T3 (thyroid hormone)?
7. Which type of hormone is PTH (parathyroid hormone)?[polypeptide; catecholamine; nonpolar]
8. Which type of hormone is 1,25(OH)2D (the active form of vitamin D)?[polypeptide; catecholamine; nonpolar]

(Spelling must be correct)

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