1. Types of Hormone Molecules
Hormones are heterogeneous in their molecular size, chemical properties, and pathways of synthesis. Nitric oxide (NO) is at one extreme of the size range; the pituitary gonadotropins consisting of two subunits are among the largest of the protein hormones with molecular weights ranging between 25 and 36 kDa, depending on the extent of added carbohydrates (glycosylation). Peptide or protein hormones range from three amino acids (TRH) to over 100 per subunit. Thyroid hormone and epinephrine are derived from the amino acid tyrosine. Steroid hormones and vitamin D and its metabolites are derived from cholesterol or 7-dehydrocholesterol, respectively. Arachidonic acid, cleaved from membrane phospholipids, is the main precursor of the prostaglandins and other eicosanoids.
The initial step in the action of a hormone, the inter action with its receptor, depends to some extent on its chemical nature. Peptide and protein hormones have receptors that are membrane-spanning proteins so that the molecule does not have to enter the cell, but can deliver its message on the outside where it will be conveyed to the interior of the cell by structural changes in the receptor protein. Steroid hormones, considered to be soluble in the phospholipid bilayer, can enter the cell so that the receptors for these hormones are located either in the cytoplasm or the nucleus of the cell. The actions of these hormones are propagated by interaction of the receptor with nuclear proteins and DNA. The amino acid-derived hormones differ from one another: thyroid hormone has an intracellular receptor similar to those for the steroid hormones and epinephrine interacts with its membrane receptor.
Thus, the hormonal messaging systems have evolved using a variety of types of molecules and mechanisms of actions. Understanding these in settings of particular systems is a major focus of this book.
2. Types of Hormonal Communication Systems
Hormones are chemical messengers that send a signal within a physiological system from point A (secretion) to point B (biological action). Three variations on the anatomical and therefore functional relationship between point A and point B of these systems are illustrated in Figure 1.
Fig1. Types of hormonal signaling. Three of the ways that hormones secreted by one cell can carry out its signaling function are illustrated. The top panel shows the classical endocrine system with a specialized hormone-synthesizing cell secreting its product into the bloodstream. It is carried throughout the body and may interact with one or many distant target cells, which are distinguishable by the presence of a specific receptor for the hormone on its surface (shown) or within the cell (not illustrated). In paracrine signaling (lower left), the signaling cell, which also has many other functions, releases the hormone into the intracellular space and it moves small distances to nearby cells. These target cells also have a specific receptor for the hormone (membrane or intracellular). In paracrine signaling, the cells reached by the hormone may be of the same or different types. Finally, cells that secrete the hormone and also have receptors that bind and respond to it are displaying autocrine signaling, as shown on the lower right of the figure.
The classic systemic endocrine system is shown in the top panel. The hormone is biosynthesized (and perhaps, but not necessarily, stored) within specific cells associated with an anatomically defined endocrine gland. Upon the receipt of an appropriate physiological signal, which may take the form of either a change in the concentration of some component in the blood (e.g., another hormone, Ca2+, glucose) or a neural signal, the hormone is released into the circulation. It is transported in the bloodstream to one or more target cells, which are defined as targets by the presence of a specific high affinity receptor, either on the membrane or within the cell, for the hormone. It is what the receptor does after interacting with the hormone that determines the biological response. As will be seen in several of the chapters in this book many, if not most, hormones have numerous and diverse target cells and the response to the hormone may vary with cell type, indicating that other players in or around the target cell may affect the outcome of hormone-receptor interactions.
In some or portions of some endocrine systems the hormone-secreting cell releases its product not into the general circulation but into a closed system, such as the hypothalamic-pituitary portal system. In this case the hypothalamic-releasing hormones are released into and diluted by a limited volume, ensuring that most of the hormone molecules will be delivered to the anterior pituitary, which contains their target cells.
The lower left panel of Figure 1 shows a type of hormonal communication system that does not involve the circulatory system at all. In paracrine systems, hormones secreted from the signaling cell interact with specific high-affinity receptors in neighboring cells which are reached by diffusion: i.e., the distance from point A to point B is decreased and dilution in the bloodstream is avoided. As with endocrine systems, the nearby target cells may be all the same type or may differ from each other as illustrated. Most prostaglandins act through paracrine mechanisms. Several, if not all, of the steroid hormones act by paracrine in addition to endocrine mechanisms. For example, in the testis testosterone is not only released into the blood from the interstitial cells in which it is produced but also diffuses to nearby seminiferous tubules to support the production of sperm. IGF-1 is a protein hormone secreted into the bloodstream by the liver in response to growth hormone, but is also secreted by other cells to control the growth and differentiation of neighboring cells.
Finally, some cells both produce and respond to the same hormone. This type of system is referred to as autocrine. Examples of these systems involve growth factors and the control (or lack thereof in malignancy) of cellular proliferation.
