Chapter 40

1. Epinephrine is a derivative of an amino acid, transported in solution in the blood, and acts on cell surface receptors to trigger an intracellular signaling cascade that produces an immediate response. Estrogen is a steroid hormone that is transported in the blood in combination with a protein carrier. Since it is lipid soluble, it diffuses into target cells to bind to an intracellular receptor that is then translocated to the nucleus and alters gene expression. Responses to the hormone are mediated through the products of that gene expression, all of which takes more time than the actions of epinephrine.

2. The presence of the same hormone in two species is not an indication of closeness of their evolutionary relationships because hormone structures are highly conserved even as their functions change. Therefore distantly related species can share the same hormones.

3. A-42

   A single hormone can have different effects in the same species depending on the types of cells that express its receptors and also on the nature of the receptors themselves, which can activate different signal transduction pathways.

1. During development, the posterior pituitary is derived from an outpocketing of the brain and the anterior pituitary is derived from an outpocketing of the embryonic mouth tissue. Thus the posterior pituitary is neural tissue, and it is nerve cells that produce and release the posterior pituitary hormones, which are neurohormones. The anterior pituitary comes from gut epithelium, and the secretory cells develop from gut epithelial cells.

2. Hypothalamic neurons release tiny quantities of releasing or release-inhibiting hormones that diffuse into portal blood vessels between the hypothalamus and the anterior pituitary. These hypothalamic hormones leave the portal capillaries in the anterior pituitary and diffuse to anterior pituitary cells that have receptors for those particular release or release-inhibiting hormones. Those anterior pituitary cells respond by changing the release of their hormones, which include four tropic hormones (thyrotropin, adrenocorticotropin, and the gonadotropins LH and FSH) and growth hormone.

3. Negative feedback in the hypothalamic control of endocrine function involves the inhibitory effect of the end hormone on the hypothalamic production of the hypothalamic releasing (or release-inhibiting) hormone that controls the anterior pituitary cells that produce the tropic hormones controlling the cells or gland that produce and release the end hormone.

1. Decapitation of Rhodnius prevented molting when done 1 hour after feeding but not when done 1 week after feeding because of the time necessary for PTTH to be released and diffuse to the prothoracic gland in sufficient amounts to stimulate the release of ecdysone.

2. The female external phenotype is the default pathway in humans. That pathway is altered in normal XY individuals because of genes on the Y chromosome that stimulate the development of testes rather than ovaries. The testes produce the male steroid sex hormone that stimulates development of the male external phenotype. However, if an individual lacks receptors for the male steroid sex hormone, then it has no effect and the female phenotype develops.

3. In the prepubertal individual, sex steroids are produced in low amounts, but these low amounts provide sufficient negative feedback to the hypothalamus to inhibit the production of GnRH. As a result, the release of LH and FSH from the anterior pituitary is low. However, at the time of puberty, sensitivity of the hypothalamus to the circulating sex steroids is reduced, releasing the negative feedback control. Therefore production and release of GnRH as well as LH and FSH go up, stimulating the changes associated with puberty.

1. A major cause of hypothyroidism is lack of iodine. Without adequate iodine, the thyroid cannot secrete active T₃ and T₄. As a result there is no negative feedback on the production of TRH and TSH. The elevated TSH causes increased production of thyroglobulin and growth of the thyroid gland. A major cause of hyperthyroidism is production of an antibody to the TSH receptor that binds to the receptor and keeps it activated. The result is continuous stimulation of thyroglobulin production. Even though the individual produces active T₃ and T₄, they cannot exert negative feedback on the hypothalamic–pituitary–thyroid system.

2. Vitamins are required in the diet because they are not produced in the body. Since vitamin D is produced in the body by the action of UV light on a precursor in the skin, converting it to calciferol, it is not a vitamin. Calciferol is converted to the active form calcitriol by enzymes in the liver and kidneys. Calcitriol (vitamin D) promotes the uptake of calcium from the gut and the kidneys, thereby raising blood calcium levels.

3. Insulin controls the rate of glucose uptake by cells by stimulating the cells to insert glucose transporters (passive transporters) into the cell membrane from a pool of those receptors in the cytoplasm. The glucose transporters in the cell membrane increase the permeability of the cell to glucose, which can then diffuse into the cell as long as its concentration in the extracellular fluid is high enough.

4. Stress stimulates the release of cortisol from the adrenal cortex. Cortisol helps the body deal with short-term stress by reducing cellular uptake of glucose, elevating blood pressure, inhibiting activity of the gut and the reproductive system, and even inhibiting the activity of the immune system. In the short run, these responses make more energy available to deal with the immediate stressor. Negative feedback from cortisol, acting through the hypothalamus and the pituitary gland normally shuts off the cortisol response to short-term stress. If, however, stress becomes chronic, as in a difficult job situation, cortisol levels remain high and the resulting higher blood pressure can lead to heart disease, the impaired immune system can lead to infections and diseases, the impaired digestion can lead to ulcers, and the impaired glucose metabolism can lead to diabetes.

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2. To determine if exercise increases BDNF levels in the hippocampus, you would assay BDNF levels in the hippocampus of the exercised and non-exercised mice, obtain average values and standard deviations, and do a t-test to determine the probability that the values for the two groups are the same. If P is < 0.05, the values for the two groups are significantly different.

3. To determine if increased expression of FNDC5 in the hippocampus is sufficient to stimulate an increase in BDNF expression, you would culture some hippocampal cells in media that stimulates FNDC5 expression and some hippocampal cells in media that suppresses FNDC5 expression. You would then measure the levels of BDNF in those cultures. A t-test would reveal the probability that FNDC5 had no effect on BDNF expression. If those probabilities are < 0.05, you would conclude that differences in FNDC5 expression are sufficient to influence BDNF expression.

1. In the experiment in which irisin was injected into the mice kept on a high-fat diet, it was important to measure UCP1 expression as well as betatrophin because a relationship between irisin and UCP1 had been established earlier in exercise experiments. Therefore the measurement of UCP1 in that experiment was a positive control for activity of the injected irisin.

2. The mice were placed on a high-fat diet to model the condition of obesity and prediabetic insulin resistance.

3. The data support the hypothesis that irisin could reduce obesity and lower the risk for type II diabetes for the following reasons. Using t-tests confirms that the two groups of mice prior to irisin application did not differ in body mass. However, the irisin-treated mice showed a significant (P < 0.05) reduction in body mass, whereas the control mice showed no significant change in body mass. The irisin-treated mice had significantly lower fasting insulin levels and blood glucose levels than the control mice did, also indicating a lowered risk for type II diabetes.

1. The epinephrine in the irrigation fluid is affecting the dilator muscle fibers. When comparing the two types of surgeries, those that used the epinephrine-containing solution dilated the pupil past the 5-mm diameter and kept it dilated for a longer period of time than those surgeries that did not use the epinephrine-containing irrigation fluid. Since dilator muscle contractions are what cause the pupil to enlarge, these must be the muscle fibers affected by epinephrine.

2. Although both the constrictor muscle fibers and dilator muscle fibers are smooth muscle tissue, only the dilator muscle fibers contain a corresponding receptor protein on their cell surface that will bind to epinephrine. Thus the dilator fibers are target cells for epinephrine while the constrictor fibers are not. Once the epinephrine binds to the receptor protein on the dilator fibers, it begins a signaling cascade within the muscle fibers that promotes strong and prolonged contractions within the fibers. This produces the larger than 5-mm diameter pupil seen in the surgeries that used epinephrine-containing irrigation fluid.

3. Epinephrine affects the cardiovascular system by increasing the heart rate and blood pressure. It causes arterioles in the digestive system and skin to contract but causes the arterioles in the skeletal muscles to dilate. It causes the liver to break down glycogen into glucose and stimulates adipose tissue to break down fat into fatty acids. These different effects are stimulated by the same hormone binding to receptors on the surface of each type of cell. The reason the responses are so varied is because of what happens inside each cell type after the receptor has been activated. Each cell will have a different signaling cascade that results in different intracellular processes. The difference in processes is determined by the type of cell (cardiac muscle vs. smooth muscle vs. hepatocytes vs. adipocytes, etc.) and by the types of intracellular signaling molecules that are created.

4. A-43

   To elicit a pupillary dilation from the constrictor fibers, these muscle fibers must relax beyond their normal resting state. This is the effect of atropine. Since atropine inhibits the interaction of acetylcholine with its receptor, this must mean that acetylcholine is the neurotransmitter that stimulates constrictor fibers to contract and reduce the pupil size. It also means that there is normally a baseline level of acetylcholine that keeps the constrictor fibers somewhat contracted. Thus the autonomic nervous system controls pupil diameter by releasing both epinephrine and acetylcholine—epinephrine to cause dilator fibers to contract and enlarge the pupil, and acetylcholine to cause constrictor fibers to contract and decrease the pupil size.