An Introduction to Steroids and Negative Feedback Loops Model 1 Steroids are lipid molecules that have many functions. One example of a steroid is the hormone testosterone. Testosterone naturally occurs in the body and is highly involved in puberty. Some athletes take testosterone, or “steroids,” to get bigger, faster, and stronger. But steroid abuse can result in some strange events. For example, Jose Conseco, a famous baseball player from the 1990’s, was once stopped at the US/Mexican border for attempting to smuggle human chorionic gonadotropic (hCG), a hormone that is extracted from the urine of pregnant women. If you can understand why a big time steroid abuser is using a hormone that is secreted by pregnant women, then you can understand some of the basic physiology of homeostasis and feedback loops. 1. At puberty, healthy male gonads (i.e., testicles) will start secreting increased quantities of testosterone. a. What happens to a male at puberty? (What is the action of testosterone?) Testosterone secretion increases and acts on organs and structures in the male body, causing changes to the physical appearance. b. What happens to a young male’s physical appearance? (Try to say more than “he gets bigger.”) Muscles get bigger, voice gets deeper, reproductive organs enlarge, growth spurt, increased body hair. c. What happens to a young male’s behavior? (Example: Is he more interested in sexual activity?) May be more interested in sexual activity, increased moodiness or drowsiness, sleeping more, increased aggressiveness. 2. What is the most obvious reason for an athlete to take artificial forms of testosterone? OR, What is the desired effect of hypertestosteronism? Increased muscle mass and strength, increased bone density. 3. Do females have testosterone? If so, what organ (or glands) produces testosterone in females? What is the action of testosterone in females? Yes; produced by the ovaries. Minor role in growth, maintenance & repair of reproductive tissues. Model 2 – Hormone Regulation and Feedback System Normally, testosterone production begins in the testicles after being stimulated (“turned on” or “activated”) by Luteinizing Hormone (LH) and Follicle Stimulation Hormone (FSH) – two hormones that are produced and released by the pituitary gland. 1. Using this line art drawing of a male, identify the location of the pituitary gland and the testes. Draw lines and arrows to show the pituitary gland secreting FSH and LH that “targets” the gonads, and then show the gonads secreting testosterone. a. How does FSH and LH get to the testes? (How do hormones travel in the body?) Hormones travel to the testes through the bloodstream from one gland to another gland, tissue, or cell. Pituitary gland Testes 2. When an athlete takes artificial steroids, the natural / regular systems for stimulating testosterone production are reduced, or even shut down, due to negative feedback. Use the sample graphic below to think about the concept of homeostasis, and then write a complete sentence that explains the concept of negative feedback. Negative feedback corrects for changes in a system by increasing amounts of a hormone or substance when levels are too low, and by decreasing amounts of a hormone or substance when levels are too high. 3. High levels of testosterone (i.e., hypertestosteronism) will cause a reduction in FSH and LH levels. Predict how the testicles will respond to reduced levels of FSH and LH. The testicles would develop hypogonadism, causing decreased sperm production. 4. One of the side effects of steroid abuse is reduced sperm production and testicular feminization. Using your knowledge of medical terminology, what is “testicular feminization?” The male genitalia would slow or cease production of sperm and reduce in size, causing “feminization” of the testicles. 5. Testosterone has to be taken in cycles. Users take steroids for a couple days, and then do not use them for a couple days. When users are “off cycle,” their levels of testosterone drop and the testosterone molecules decompose into other substances. One chemical that is the product of the decay of testosterone is estradiol (a form of estrogen). a. Predict how estradiol (estrogen) might affect a male athlete. Estrogen may cause breast development, low sex drive, infertility, prostate problems, and weight gain. b. What are some other unwanted effects of hypertestosteronism? Increased anger, agitation, restlessness, acne Model 3 – The Nervous System’s Involvement with the Production of Testosterone The pituitary gland and the testes are both organs of the endocrine system and are integral to the production and regulation of testosterone, but the nervous system is involved as well. A structure within the brain that is closely associated with the pituitary gland is the hypothalamus. (The image to the right shows both the hypothalamus and the pituitary gland.) The hypothalamus communicates with the pituitary via neurons that secrete “neurohormones” - also called “releasing hormones” because they cause their target tissues (the pituitary) to secrete hormones. One of the neurohormones secreted by the hypothalamus is Gonadotropin Releasing Hormone (GnRH), which stimulates the pituitary gland to secrete FSH and LH. 1. Make a line drawing of a male and show the location of the following structures: hypothalamus, pituitary, and testes. Also on the drawing, show how secretions from the hypothalamus are linked to secretions of the testicles. (Hint – use arrows and the names of the hormones / neurohormones involved.) Drawing should include hypothalamus associated with the pituitary gland in the brain. Arrows from hypothalamus indicate release of GnRH to pituitary gland; arrows from pituitary gland indicate release of FSH and LH to testes; arrows from testes indicate testosterone release to tissues. 2. The hypothalamus contains receptors that bind with testosterone; that is, testosterone “targets” the hypothalamus. However, this stimulation is negative – it is part of a negative feedback loop. a. Predict what happens to the production of GnRH when there are high levels of testosterone molecules in the body (i.e., lots of testosterone molecules bound to the receptors on the hypothalamus). GnRH production would likely decrease or be suppressed. b. What happens to the production of LH and FSH when there are high levels of testosterone molecules bound to the receptors on the hypothalamus? LH and FSH production would likely decrease or be suppressed. c. What happens to the testosterone production in the testes when there are high levels of testosterone molecules bound to the receptors on the hypothalamus? Testosterone production would likely decrease or be suppressed. 3. In the space below, make a drawing that shows the above feedback loop. Feedback loop should show high testosterone causing low GnRH and LH/FSH levels. Application Questions: 1. Human Chorionic Gonadotropin (hCG), a hormone naturally produced and secreted by the placenta in pregnant females, will stimulate the gonads (both the testes and the ovaries). Explain why a long-term steroid abuser, such as Jose Canseco, might want to purchase and use hCG. The hormone will stimulate the testes to maintain size and sperm production, preventing the decrease in size seen with steroid usage. 2. Some people take artificial forms of estrogen in a procedure broadly called “hormone replacement therapy.” What types of people would be candidates for this type of therapy? Pre- and post-menopausal women lacking estrogen, people with decreased muscle tone or bone density.