Endocrinology is the study of chemical communication systems that provide the means to control a huge number of physiologic processes. Like other communication networks, endocrine systems contain transmitters, signals and receivers that are called, respectively, hormone producing cells, hormones and receptors. The first step in understanding endocrinology is to explore the meaning of such terms as hormone, receptor and target cell, and to obtain an understanding of how chemical communication is controlled Hormones, Receptors and Target Cells
What exactly are hormones and how are they different from “non-hormones”? Hormones are chemical messengers secreted into blood or extracellular fluid by one cell that affect the functioning of other cells. Most hormones circulate in blood, coming into contact with essentially all cells. However, a given hormone usually affects only a limited number of cells, which are called target cells. A target cell responds to a hormone because it bears receptors for the hormone. In other words, a particular cell is a target cell for a hormone if it contains functional receptors for that hormone, and cells which do not have such a receptor cannot be influenced directly by that hormone. Reception of a radio broadcast provides a good analogy. Everyone within range of a transmitter for National Public Radio is exposed to that signal (even if they don’t contribute!). However, in order to be a NPR target and thus influenced directly by their broadcasts, you have to have a receiver tuned to that frequency.
Hormone receptors are found either exposed on the surface of the cell or within the cell, depending on the type of hormone. In very basic terms, binding of hormone to receptor triggers a cascade of reactions within the cell that affects function. Additional details about receptor structure and function are provided in the section on hormone mechanism of action. A traditional part of the definition of hormones described them as being secreted into blood and affecting cells at distant sites. However, many of the hormones known to act in that manner have been shown to also affect neighboring cells or even have effects on the same cells that secreted the hormone. Nonetheless, it is useful to be able to describe how the signal is distributed for a particular hormonal pathway, and three actions are defined: * Endocrine action: the hormone is distributed in blood and binds to distant target cells. * Paracrine action: the hormone acts locally by diffusing from its source to target cells in the neighborhood. * Autocrine action: the hormone acts on the same cell that produced it.Two important terms are used to refer to molecules that bind to the hormone-binding sites of receptors: * Agonists are molecules that bind the receptor and induce all the post-receptor events that lead to a biologic effect. In other words, they act like the “normal” hormone, although perhaps more or less potently.
Natural hormones are themselves agonists and, in many cases, more than one distinct hormone binds to the same receptor. For a given receptor, different agonists can have dramatically different potencies. * Antagonists are molecules that bind the receptor and block binding of the agonist, but fail to trigger intracellular signalling events. Antagonists are like certain types of bureaucrats – they don’t themselves perform useful work, but block the activities of those that do have the capacity to contribute. Hormone antagonists are widely used as drugs.Finally, a comment on the names given hormones and what some have called the tyranny of terminology. Hormones are inevitably named shortly after their discovery, when understanding is necessarily rudimentary. They are often named for the first physiologic effect observed or for their major site of synthesis. As knowledge and understanding of the hormone grow, the original name often appears inappropriate or too restrictive, but it has become entrenched in the literature and is rarely changed. In other situations, a single hormone will be referred to by more than one name. The problem is that the names given to hormones often end up being either confusing or misleading. The solution is to view names as identifiers rather than strict guidelines to source or function. | Mechanisms of Hormone Action: Introduction and Index|
Immediately after discovery of a new hormone, a majority of effort is devoted to delineating its sites of synthesis and target cells, and in characterizing the myriad of physiologic responses it invokes. An equally important area of study is to determine precisely how the hormone acts to change the physiologic state of its target cells – its mechanism of action. Understanding mechanism of action is itself a broad task, encompassing structure and function of the receptor, how the bound receptor transduces a signal inside the cell and the end effectors of that signal. This information is not only of great interest to basic science, but critical to understanding and treating diseases of the endocrine system, and in using hormones as drugs. | | Functional Anatomy of the Hypothalamus and Pituitary Gland
The hypothalamus is a region of the brain that controls an immense number of bodily functions. It is located in the middle of the base of the brain, and encapsulates the ventral portion of the third ventricle.
The pituitary gland, also known as the hypophysis, is a roundish organ that lies immediately beneath the hypothalamus, resting in a depression of the base of the skull called the sella turcica (“Turkish saddle”). In an adult human or sheep, the pituitary is roughly the size and shape of a garbonzo bean. The image to the right, from the Visible Human Project, shows these anatomical relationships in the Visible Woman (click on the image to see a larger, unlabeled image).
Careful examination of the pituitary gland reveals that it composed of two distinctive parts: * The anterior pituitary or adenohypophysis is a classical gland composed predominantly of cells that secrete protein hormones. * The posterior pituitary or neurohypophysis is not a separate organ, but an extension of the hypothalamus. It is composed largely of the axons of hypothalamic neurons which extend downward as a large bundle behind the anterior pituitary. It also forms the so-called pituitary stalk, which appears to suspend the anterior gland from the hypothalamus. The image to the right shows a frontal view of a sheep pituitary gland and hypothalamus. The posterior gland can be seen peeking out behind the anterior gland; pass your mouse cursor over the image for labels (image courtesy of Dr. Terry Nett). The anterior and posterior pituitary have separate embryological origins. In many mammals, there is also an intermediate lobe (pars intermedia) between the anterior and posterior pituitary. A key to understanding the endocrine relationship between hypothalamus and anterior pituitary is to appreciate the vascular connections between these organs.
As will be emphasized in later sections, secretion of hormones from the anterior pituitary is under strict control by hypothalamic hormones. These hypothalamic hormones reach the anterior pituitary through the following route: * A branch of the hypophyseal artery ramifies into a capillary bed in the lower hypothalamus, and hypothalmic hormones destined for the anterior pituitary are secreted into that capillary blood. * Blood from those capillaries drains into hypothalamic-hypophyseal portal veins. Portal veins are defined as veins between two capillary beds; the hypothalamic-hypophyseal portal veins branch again into another series of capillaries within the anterior pituitary. * Capillaries within the anterior pituitary, which carry hormones secreted by that gland, coalesce into veins that drain into the systemic venous blood. Those veins also collect capillary blood from the posterior pituitary gland. This pattern of vascular connections is presented diagramatically below. Note also the hypothalamic-hypophyseal portal vessels in the image of a real pituitary gland seen above.
The utility of this unconventional vascular system is that minute quantities of hypothalamic hormones are carried in a concentrated form directly to their target cells in the anterior pituitary, and are not diluted out in the systemic circulation Functional Anatomy of the Thyroid and Parathyroid Glands
Thyroid glands are located in the neck, in close approximation to the first part of the trachea. In humans, the thyroid gland has a “butterfly” shape, with two lateral lobes that are connected by a narrow section called the isthmus. Most animals, however, have two separate glands on either side of the trachea. Thyroid glands are brownish-red in color. Close examination of a thyroid gland will reveal one or more small, light-colored nodules on or protruding from its surface – these are parathyroid glands (meaning “beside the thyroid”). The image to the right shows a canine thyroid gland and one attached parathyroid gland. The microscopic structure of the thyroid is quite distinctive. Thyroid epithelial cells – the cells responsible for synthesis of thyroid hormones – are arranged in spheres called thyroid follicles. Follicles are filled with colloid, a proteinaceous depot of thyroid hormone precursor. In the low (left) and high-magnification (right) images of a cat thyroid below, follicles are cut in cross section at different levels, appearing as roughly circular forms of varying size. In standard histologic preparations such as these, colloid stains pink.
In addition to thyroid epithelial cells, the thyroid gland houses one other important endocrine cell. Nestled in spaces between thyroid follicles are parafollicular or C cells, which secrete the hormone calcitonin. The structure of a parathyroid gland is distinctly different from a thyroid gland. The cells that synthesize and secrete parathyroid hormone are arranged in rather dense cords or nests around abundant capillaries. The image below shows a section of a feline parathyroid gland on the left, associated with thyroid gland (note the follicles) on the right.
Gastrointestinal Hormones: Introduction and Index
Digesting, absorbing and assimilating a meal requires precise coordination of a huge number of physiologic processes. Control over gastrointestinal function is, as one would expect, provided by nervous and endocrine systems. The hormones most important in controlling digestive function are synthesized within the gastrointestinal tract by cells scattered in the epithelium of the stomach and small intestine. These endocrine cells and the hormones they secrete are referred to as the enteric endocrine system. Interestingly, most if not all “GI hormones” are also synthesized in the brain. The following discussions assume some familiarity with the anatomy and physiology of the digestive system.