Introduction to Endocrinology

Polypeptide and Protein Hormones Are Stored in Secretory Vesicles Until Needed

Most of the hormones in the body are polypeptides and proteins. These hormones range in size from small peptides with as few as three amino acids (e.g., thyrotropin-releasing hormone) to proteins with almost 200 amino acids (e.g., growth hormone and prolactin). In general, polypeptides with 100 or more amino acids are called proteins, and those with fewer than 100 amino acids are referred to as peptides.

Protein and peptide hormones are synthesized on the rough end of the endoplasmic reticulum of the different endocrine cells, in the same fashion as most other proteins ( Figure 75-2 ). They are usually synthesized first as larger proteins that are not biologically active (preprohormones) and are cleaved to form smaller prohormones in the endoplasmic reticulum. These prohormones are then transferred to the Golgi apparatus for packaging into secretory vesicles. In this process, enzymes in the vesicles cleave the prohormones to produce smaller, biologically active hormones and inactive fragments. The vesicles are stored within the cytoplasm, and many are bound to the cell membrane until their secretion is needed. Secretion of the hormones (as well as the inactive fragments) occurs when the secretory vesicles fuse with the cell membrane and the granular contents are extruded into the interstitial fluid or directly into the blood stream by exocytosis.

In many cases, the stimulus for exocytosis is increased cytosolic calcium concentration caused by depolarization of the plasma membrane. In other cases, stimulation of an endocrine cell surface receptor causes increased cyclic adenosine monophosphate (cAMP) and subsequently activation of protein kinases that initiate secretion of the hormone. The peptide hormones are water soluble, allowing them to enter the circulatory system easily, where they are carried to their target tissues.

Steroid Hormones Are Usually Synthesized From Cholesterol and Are Not Stored

Steroid hormones have a chemical structure that is similar to cholesterol, and in most cases are synthesized from cholesterol. They are lipid soluble and consist of three cyclohexyl rings and one cyclopentyl ring combined into a single structure ( Figure 75-3 ).

Although there is usually very little hormone storage in steroid-producing endocrine cells, large stores of cholesterol esters in cytoplasm vacuoles can be rapidly mobilized for steroid synthesis after a stimulus. Much of the cholesterol in steroid-producing cells comes from the plasma, but there is also de novo synthesis of cholesterol in steroid-producing cells. Because steroids are highly lipid soluble, once they are synthesized, they can simply diffuse across the cell membrane and enter the interstitial fluid and then the blood.

Amine Hormones Are Derived From Tyrosine

The two groups of hormones derived from tyrosine, the thyroid and the adrenal medullary hormones, are formed by the actions of enzymes in the cytoplasmic compartments of glandular cells. The thyroid hormones are synthesized and stored in the thyroid gland and incorporated into macromolecules of the protein thyroglobulin, which is stored in large follicles within the thyroid gland. Hormone secretion occurs when the amines are split from thyroglobulin, and the free hormones are then released into the blood stream. After entering the blood, most of the thyroid hormones combine with plasma proteins, especially thyroxine-binding globulin, which slowly releases the hormones to the target tissues.

Epinephrine and norepinephrine are formed in the adrenal medulla, which normally secretes about four times more epinephrine than norepinephrine. Catecholamines are taken up into preformed vesicles and stored until secreted. Similar to the protein hormones stored in secretory granules, catecholamines are also released from adrenal medullary cells by exocytosis. Once the catecholamines enter the circulation, they can exist in the plasma in free form or in conjugation with other substances.

Hormone Secretion After a Stimulus and Duration of Action of Different Hormones.

Some hormones, such as norepinephrine and epinephrine, are secreted within seconds after the gland is stimulated and may develop full action within another few seconds to minutes; the actions of other hormones, such as thyroxine or growth hormone, may require months for full effect. Thus, each of the different hormones has its own characteristic onset and duration of action—each tailored to perform its specific control function.

Concentrations of Hormones in the Circulating Blood and Hormonal Secretion Rates

The concentrations of hormones required to control most metabolic and endocrine functions are incredibly small. Their concentrations in the blood range from as little as 1 picogram (which is one millionth of one millionth of a gram) in each milliliter of blood up to at most a few micrograms (a few millionths of a gram) per milliliter of blood. Similarly, the rates of secretion of the various hormones are extremely small, usually measured in micrograms or milligrams per day. We shall see later in this chapter that highly specialized mechanisms are available in the target tissues that allow even these minute quantities of hormones to exert powerful control over the physiological systems.

Negative Feedback Prevents Overactivity of Hormone Systems.

Although the plasma concentrations of many hormones fluctuate in response to various stimuli that occur throughout the day, all hormones studied thus far appear to be closely controlled. In most cases, this control is exerted through negative feedback mechanisms (described in Chapter 1 ) that ensure a proper level of hormone activity at the target tissue. After a stimulus causes release of the hormone, conditions or products resulting from the action of the hormone tend to suppress its further release. In other words, the hormone (or one of its products) has a negative feedback effect to prevent oversecretion of the hormone or overactivity at the target tissue. Feedback regulation of hormones can occur at all levels, including gene transcription and translation steps involved in the synthesis of hormones and steps involved in processing hormones or releasing stored hormones.

The controlled variable is sometimes the degree of activity of the target tissue rather than the synthesis or secretory rates of the hormone. Therefore, only when the target tissue activity rises to an appropriate level will feedback signals to the endocrine gland become powerful enough to slow further synthesis and secretion of the hormone.