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, usually by exocytosis. 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.

Different Modes of Cell Signaling

Endocrine signaling can be contrasted with two other modes of signaling: neural signaling and paracrine signaling. The different modes of signaling are schematized in the figure.

A key difference is the distance that the regulatory molecule travels to reach its target. Neurons are connected to their target cells via synapses.  A neurotransmitter crossing a synaptic cleft will travel between 10 and 20 nanometers. A paracrine will travel only a few millimeters before it is broken down, so it can only act on nearby cells. By contrast, hormones travel via the circulation to reach their targets, which may be multiple tissues that are distant from each other and the endocrine cells. Thus, hormones could be said to have systemic efffects.

Note that the timing involved in endocrine signaling also differs markedly from neural signaling. Neural signaling is brief and discrete, generally beginning and ending in less than a second. The timing of endocrine signaling is longer: the hormone takes more time to reach its target, the response of target cells takes longer, and hormones are more stable and capable of signaling over longer times.

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 peptide 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 delivery into secretory vesicles.

Peptide hormones are synthesized in the rough endoplasmic reticulum (rough ER). Usually, a peptide 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 alpha-melanocyte-stimulating hormone (alpha-MSH).

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.  Many polar hormones signal via receptors that are coupled to trimeric G-proteins.

The nonpolar hormones are the steroid hormones and thyroid hormones. The steroid hormones are synthesized through chemical modification of cholesterol. Thyroid hormones are initially synthesized as part of a large protein precusor 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 via intracellular 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 enzymatically modified in target tissues. Metabolism of hormone may inactivate the hormone, but it may also act to 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'-tetraiodothyronine 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 peptide 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 peptide hormones synthesized?
4. Name the prohormone from which ACTH and alpha-MSH are produced.
5. Dopamine, epinephrine, and norepinephrine are collectively referred to as the ______________.
6. Which hormone binds to an intracellular receptor, dopamine or thyroid hormone?
7. Which type of hormone is PTH (parathyroid hormone)?[peptide; catecholamine; steroid]
8. Which type of hormone is 1,25(OH)2D (the active form of vitamin D)?[peptide; catecholamine; steroid]

(Spelling must be correct)

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