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The word hormone was first used in Modern Medicine by the English physician Ernest Henry Starling (1866-1927), when he described the chemical messengers that travel through the body from the cells of production to a target organ. This word comes directly from the Greek verb ὁρμῶ (ormo), that means “to lunge” or “rush forward” as these messengers “rush” from the cells of origin toward the target organ. Today, the term hormone refers to those chemical messengers that travel through the bloodstream between cellular sites and regulate physiology and behavior. Hormones belong to 3 major classes: eicosanoids, steroids, and peptidic products. Even though isolated cells from organs such as the heart or the intestines secrete hormones and hence can be considered endocrine cells, endocrine glands are typically defined as those specific regions of the body where endocrine cells are concentrated. These regions include the hypothalamus, pituitary, thyroid, parathyroids, thymus, pancreas, pineal, adrenals, ovaries, and testes. As hormones are the only way outside of the nervous system for our organs to communicate, they are involved in almost all physiological processes including digestion, respiration, lactation, reproduction, response to stress, movement, growth, and many others. Given their ubiquitous roles in cellular physiology, it is not surprising they are also critical to both tumorigenesis and tumor progression. Many common cancer types are driven by inappropriate hormone signaling, including prostate, breast, endometrium, ovary, thyroid, testes, and bone cancers (Henderson et al, 1982). In this chapter, we will focus primarily on breast and prostate cancers to illustrate the relationship between hormones and cancer as they are among the most common causes of cancer-related death in women and men.
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The relationship between prostate enlargement and hormones produced by the testes has long been recognized. Although the chemical nature of androgens was not known, it was reported in 1895 that surgical castration (orchiectomy) of elderly men with prostate enlargement, presumably due to benign prostatic hyperplasia, resulted in rapid atrophy of prostatic tissue. Following the isolation of “testosterone” as the most potent androgenic compound in the testes in 1935, Huggins and Hodges later demonstrated the efficacy of surgical orchiectomy for the treatment of metastatic prostate cancer, for which Huggins received the Nobel Prize in Physiology or Medicine in 1966. Similarly, a link between estrogen and breast cancer growth was established at the end of the 19th century, when Beatson demonstrated that removal of ovaries (oophorectomy) helped in the treatment of metastatic breast cancer in some premenopausal women. However, a molecular basis for this observation was not forthcoming until the 1960s with the discovery of the estrogen receptor, followed by the demonstrated expression of estrogen receptors in some human breast tumors by Elwood Jensen.
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Evidence for a direct link between sex steroids and the carcinogenic process leading to breast and prostate tumors, was first provided by Robert Noble. He reported that prolonged exposure to estrogen, androgen, or combinations of the two, caused breast ...