1. Discuss the concepts of homeostasis and feedback in regulatory physiology. Use production of thyroid hormones as an example. Homeostasis is the physiological responses that occur in response to a changing environment to try to maintain the internal environment as constant as possible Examples of internal conditions that are regulated in the mammalian system are temperature, glucose, pH, oxygen, salt. Not all animals regulate all internal conditions – some conform to the external environment, for example in cold blooded animals internal temperature changes as the external temperature changes. Homeostatic regulators are effective only over a limited range of external input. Extreme external conditions can not be overcome by homeostatic responses. Feedback is the principle in which an external parameter is compared to an internal set point by a coordinating centre. The centre intiates a response from effector tissue/organs if there is a difference between the set point and the external variable. Negative feedback is used extensively in physiological systems to decrease a response once it is started. Positive feedback is used more rarely to increase a response once it has started. Thyroid hormone: Hypothalamus is responsive to temperature. If it is colder than the set point TRH is released, which causes TSH to be produced by the anterior pituitary and causes it to produce the thyroid hormones, T3 and T4. These act on many target tissues to increase their metabolic rate, in part by the increased production of Na,K ATPase. Increased metabolic rate produces heat. The homesotatic response is therefore to increase body temperature.Negative feedback in this sytem involves T3 and T4 decreasing the production of TRH from the hypothalamus. 2. Compare and contrast the roles lipid-soluble and lipid-insoluble hormones and their mode of action. Use one example for each type of hormone. Lipid soluble – any steroid (cortisol, aldosterone, testosterone, estrogen) or thyroid hormones Lipid-insoluble – peptide or protein (insulin, ACTH etc), catecholamine (norepinephrine) Both types initiate their effects by interacting with receptors Both types are produced and secreted They can all act on distant target tissues However, the lipid solubility confers on them different functions: Lipid-insoluble must interact with a plasma membrane receptor on the target cells. Therefore, these initiate an intracellular signalling cascade usually involving G protein coupled receptors, second messenger systems and the activation of protein kinases. Protein kinases then have the ability to alter the function of multiple intracellular functions (ion channels, pumps, other enzymes). These systems often have amplification built into them where activation of one receptor can lead to a larger effect, i.e. production of 1000s of second messengers. The time course of action of these hormones is short (mins – hours) in comparison to lipid soluble. Lipid- soluble hormones can diffuse through the plasma membrane. They are often transported in the circulation in association with carrier molecules, which are not lipid soluble. These hormones interact with cytoplasmic or nuclear receptors and the intiate transcription of target genes. They intiate a repsonse more slowly than lipid insoluble hormones, but the effects last longer (days). 3. Describe the role of the corpus luteum in the female menstrual cycle and its role if a pregnancy occurs. The corpus luteum develops from the follicle after ovulation, but degenerates after 14 days It secretes high amounts of progesterone and a little less estrogen. Progesterone and estrogen are important for enodmetrial development of the uterus and inhibiting myometrial contractions (progesterone) High amounts of progesterone also contribute to feedback inhibtion of GnRH release from the hypothalamus, thus preventing ovulation If a pregnancy occurs, the trophoblast secrete human chorionic gonadotropin which maintains the corpus luteum and allows it to produce progesterone and estrogen until this function is taken over by the placenta. 1. Botulinum toxin (BoTox) is effective at smoothing wrinkles in the skin because it: a. inhibits synaptic transmission by cleaving a SNARE protein b. blocks the reuptake of acetylcholine c. blocks voltage gated Ca+ channels in the nerve terminal d. removes synaptotagmin from synaptic vesicles 2. Serotonin might act as an excitatory and inhibitory neurotransmitter because a. it activates both ligand gated ion channels and G protein coupled receptors b. some synapses can block the reuptake of serotonin c. some neurons have a high concentration of K+ inside the cell d. serotonin synapses are blocked by magnesium ions. 3. Why is the Na+ / K+ pump called an electrogenic pump? a. It moves Na+ ouside the cell b. It moves ions against their concentration gradient c. It requires ATP to move K+ inside the cell d. It moves less K+ inside than Na+ outside