J. Thordir. Southern Utah University.
Thus discount suhagra 100mg online erectile dysfunction bph, Jak-STAT receptors have a more direct route for propagation of the signal to the nucleus than tyrosine kinase receptors generic 100mg suhagra fast delivery impotence pump. Although Jak is an acronym for Each receptor monomer has an extracellular domain, a membrane-spanning janus kinase, it has been sug- region, and an intracellular domain. As the cytokine binds to these receptors, they gested that it stands for “just form dimers (either homodimers or heterodimers, between two distinct receptor mol- another kinase”. It was named for Janus, a ecules) and may cluster (Fig. The activated Jaks phosphorylate each other two-headed god of the Romans. STATs are inactive in the cytoplasm until they bind to the receptor complex, where they are also phosphorylated by the bound JAK. Phosphorylation changes the conformation of the STAT, causing it to dissociate from the receptor and dimerize with another phosphorylated STAT, thereby forming an activated transcription factor. The STAT dimer translocates to the nucleus and binds to a response element on DNA, thereby regulating gene transcription. There are many different STAT proteins, each with a slightly different amino acid sequence. Receptors for different cytokines bind different STATs, which then form heterodimers in various combinations. This microheterogeneity allows differ- ent cytokines to target different genes. Receptor Serine/Threonine Kinases Proteins in the transforming growth factor superfamily use receptors that have ser- ine/threonine kinase activity and associate with proteins from the Smad family, which are gene-specific transcription factors (see Fig. This superfamily includes transforming growth factor (TGF- ), a cytokine/hormone involved in tissue repair, immune regulation, and cell proliferation, and bone morphogenetic proteins (BMPs), which control proliferation, differentiation, and cell death during development. STATs dissociate from receptor, dimerize P P P P P STAT 1. Jaks phosphorylate P P cytokines, dimerize, each other and the P and bind Jaks receptor 3. CHAPTER 11 / CELL SIGNALING BY CHEMICAL MESSENGERS 197 TGF-β P P S P P S S R-Smad Type II P P S S Co-Smad R-Smad 1. R-Smad complexes to Type II receptor phosphorylates phosphorylates R-Smad with Co-Smad and Type I receptor migrates to nucleus Fig. TGF- (transforming growth factor ), which is composed of two identical subunits, communicates through a receptor dimer of type I and type II subunits that have serine kinase domains. The type I receptor phosphorylates an R-Smad (receptor-specific Smad), which binds a Co-Smad (common Smad, also called Smad 4). A simplified version of TGF- 1 binding to its receptor complex and activating Smads is illustrated in Fig. The activated type II receptor recruits a type I receptor, which it phosphorylates at a serine residue, forming an activated receptor complex. The type I receptor then binds a receptor-specific Smad protein (called R-Smads), which it phosphorylates at serine residues. The phosphorylated R-Smad undergoes a conformational change and dissociates from the receptor. It then forms a complex with another member of the Smad family, Smad 4 (Smad 4 is known as the com- mon Smad, Co-Smad, and is not phosphorylated). The Smad complex, which may contain several Smads, translocates to the nucleus, where it activates or inhibits the transcription of target genes. Receptors for different ligands bind different Smads, which bind to different sites on DNA and regulate the transcription of different genes. Signal Transduction through Heptahelical Receptors The heptahelical receptors are named for their 7-membrane spanning domains, which are -helices (see Fig. Although hun- dreds of hormones and neurotransmitters work through heptahelical receptors, the extracellular binding domain of each receptor is specific for just one polypeptide hormone, catecholamine, or neurotransmitter (or its close structural analog).
Hormones of the female menstrual cycle follow a The pituitary (pih-TU-ih-tar-e) suhagra 100mg low price erectile dysfunction filthy frank, or hypophysis (hi-POF- monthly pattern cheap 100mg suhagra mastercard erectile dysfunction remedies diabetics. It is lo- cated in a saddlelike depression of the sphenoid bone just Checkpoint 12-2 Hormones levels are normally kept within a specific range. What is the most common method used to regu- posterior to the point where the optic nerves cross. The gland is divided into two ◗ The Endocrine Glands and Their parts, the anterior lobe and the posterior lobe (Fig. Hormones The pituitary is often called the master gland because The remainder of this chapter deals with hormones and it releases hormones that affect the working of other the tissues that produce them. Refer to Figure 12-2 to lo- glands, such as the thyroid, gonads (ovaries and testes), cate each of the endocrine glands as you study them. These Pancreatic releasing hormones travel to the ante- islets rior pituitary by way of a special type of circulatory pathway called a portal system. By this circulatory “detour,” Ovaries some of the blood that leaves the hy- Testes pothalamus travels to capillaries in the anterior pituitary before returning to the heart. As the blood circulates through the capillaries, it delivers the hormones that stimulate the release of anterior pituitary secretions. Hypo- thalamic releasing hormones are indi- cated with the abbreviation RH added to an abbreviation for the name of the Figure 12-2 The endocrine glands. For example, the 248 CHAPTER TWELVE Table 12•1 The Endocrine Glands and Their Hormones GLAND HORMONE PRINCIPAL FUNCTIONS Anterior pituitary GH (growth hormone) Promotes growth of all body tissues TSH (thyroid-stimulating hormone) Stimulates thyroid gland to produce thyroid hormones ACTH (adrenocorticotropic hormone) Stimulates adrenal cortex to produce cortical hor- mones; aids in protecting body in stress situations (injury, pain) PRL (prolactin) Stimulates secretion of milk by mammary glands FSH (follicle-stimulating hormone) Stimulates growth and hormone activity of ovarian follicles; stimulates growth of testes; promotes development of sperm cells LH (luteinizing hormone); ICSH (interstitial Causes development of corpus luteum at site of cell-stimulating hormone) in males ruptured ovarian follicle in female; stimulates secretion of testosterone in male Posterior pituitary ADH (antidiuretic hormone) Promotes reabsorption of water in kidney tubules; at high concentration stimulates constriction of blood vessels Oxytocin Causes contraction of uterine muscle; causes ejection of milk from mammary glands Thyroid Thyroxine (T4) and triiodothyronine(T3) Increases metabolic rate, influencing both physical and mental activities; required for normal growth Calcitonin Decreases calcium level in blood Parathyroids Parathyroid hormone (PTH) Regulates exchange of calcium between blood and bones; increases calcium level in blood Adrenal medulla Epinephrine and norephinephrine Increases blood pressure and heart rate; activates cells influenced by sympathetic nervous system plus many not affected by sympathetic nerves Adrenal cortex Cortisol (95% of glucocorticoids) Aids in metabolism of carbohydrates, proteins, and fats; active during stress Aldosterone (95% of mineralocorticoids) Aids in regulating electrolytes and water balance Sex hormones May influence secondary sexual characteristics Pancreatic islets Insulin Needed for transport of glucose into cells; required for cellular metabolism of foods, especially glucose; decreases blood sugar levels Glucagon Stimulates liver to release glucose, thereby increasing blood sugar levels Testes Testosterone Stimulates growth and development of sexual organs (testes, penis) plus development of secondary sexual characteristics, such as hair growth on body and face and deepening of voice; stimulates maturation of sperm cells Ovaries Estrogens (e. In- uretic hormone, or ADH, and oxytocin) are actually pro- hibiting hormones suppress both growth hormone, duced in the hypothalamus and stored in the posterior pi- which stimulates growth and metabolism, and prolactin, tuitary. Their release is controlled by nerve impulses that which stimulates milk production in the mammary travel over pathways (tracts) between the hypothalamus glands. These inhibiting hormones are abbreviated GH- and the posterior pituitary. THE ENDOCRINE SYSTEM: GLANDS AND HORMONES 249 Table 12•2 Disorders Associated with Endocrine Dysfunction HORMONE EFFECTS OF HYPERSECRETION EFFECTS OF HYPOSECRETION Growth hormone Gigantism (children), acromegaly (adults) Dwarfism (children) Antidiuretic hormone Syndrome of inappropriate antidiuretic Diabetes insipidus hormone (SIADH) Aldosterone Aldosteronism Addison disease Cortisol Cushing syndrome Addison disease Thyroid hormone Graves disease, thyrotoxicosis Infantile hypothyroidism (cretinism) in chil- dren; myxedema in adults Insulin Hypoglycemia Diabetes mellitus Parathyroid hormone Bone degeneration Tetany (muscle spasms) Internal-external stimuli Neurotransmitters Hypothalamus 12 Releasing hormones secreted ADH Oxytocin Infundibulum Portal system Posterior pituitary Hormones feed back to anterior pituitary Anterior pituitary and hypothalamus Breast Oxytocin Thyroid TSH ADH Uterus Thyroid hormones ACTH Adrenal Kidney PRL FSH Ovary FSH GH Adrenocorticosteroids LH LH (ICSH) Estrogen Corpus Breast luteum Testes Bone and Progesterone soft tissues Testosterone Figure 12-3 The hypothalamus, pituitary gland, and target tissues. Arrows indicate the hormones’ target issues and feedback pathways. ZOOMING IN What two structures does the infundibulum connect? Large amounts of this hormone cause contraction of smooth muscle in blood vessel walls and raise blood pressure. Hormones of the Anterior Lobe Inadequate amounts of ADH cause excessive water loss and result in a disorder called diabetes insipidus. This ◗ Growth hormone (GH), or somatotropin (so-mah-to- type of diabetes should not be confused with diabetes TRO-pin), acts directly on most body tissues, promot- mellitus, which is due to inadequate amounts of in- ing protein manufacture that is essential for growth. GH causes increase in size and height to occur in youth, ◗ Oxytocin (ok-se-TO-sin) causes contractions of the before the closure of the epiphyses of long bones. A uterus and triggers milk ejection from the breasts. It also stimulates the liver to Box 12-1 offers information on melanocyte-stimulating release fatty acids for energy in time of stress. Tumors of the Pituitary The effects of pituitary tu- ◗ Follicle-stimulating hormone (FSH) stimulates the devel- mors depend on the cell types in the excess tissue. Some opment of eggs in the ovaries and sperm cells in the testes. A person who develops ovulation in females and sex hormone secretion in both such a tumor in childhood will grow to an abnormally tall males and females; in males, the hormone is sometimes stature, a condition called gigantism (ji-GAN-tizm) (see called interstitial cell–stimulating hormone (ICSH). Although people with this condition are large, they are usually very weak. FSH and LH are classified as gonadotropins (gon-ah- If the GH-producing cells become overactive in the do-TRO-pinz), hormones that act on the gonads to regu- adult, a disorder known as acromegaly (ak-ro-MEG-ah- late growth, development, and function of the reproduc- le) develops. In acromegaly, the bones of the face, hands, tive systems in both males and females. The fingers resemble a spatula, and the face takes on a coarse appearance: the nose widens, the Hormones of the Posterior Lobe lower jaw protrudes, and the forehead bones may bulge. Box 12-1 A Closer Look Melanocyte-Stimulating Hormone: More Than a Tan?
They may be able to get feet flat purchase suhagra 100mg without prescription erectile dysfunction lisinopril, often with significant plano- valgus order 100 mg suhagra fast delivery erectile dysfunction devices. Many of the toe walkers have varus foot position associated with equinus. Transverse plane deformities are common, with both tibial torsion and femoral anteversion. Spasticity tends to include the hip, knee, and ankle almost equally. These children have to be closely monitored for spastic hip disease, which will occur in a significant number and requires early adduc- tor lengthening. Often, these children are best treated with solid AFOs until they are 4 or 5 years of age. Physical therapy is the mainstay of treatment, with the focus being the same as with children with moderate involvement. The patterns of diplegia are more difficult to define than those of hemi- plegia. It is better to divide the stages or ages These children seldom have significant benefit from Botox because of the dif- rather than pattern of involvement. Children fuse widespread involvement of the increased spasticity. By middle child- Surgical treatment planning is usually focused at the interface between early hood, they often develop a crouched gait childhood and middle childhood. By 4 or 5 years of age, children are reach- pattern which, if left untreated, gets rapidly ing a plateau in neurologic development and the rate of learning motor and worse during the adolescent growth period. Socially, children are preparing to enter This problem may drive a child into a wheel- kindergarten or first grade if they have adequate cognitive skills. Some chil- dren in middle childhood start to back-knee, tively high functioning children, the goal should be to have the gait impair- and this may become worse in adolescence to ment surgically corrected and rehabilitation completed before entering first the point where it causes severe knee pain if grade. Entering first grade is a significant transition point for many children it is not addressed again, causing the child to as they change from primary gross motor skills orientation to primary fine mo- end up in a wheelchair. This transition period should include decreasing physical therapy and transitioning to normal age-appropriate athletic activities that individual children’s functional levels and community ambulatory abilities allow. For example, having a child play soccer 2 days a week with a team would be better than spending that time in physical ther- apy doing medically oriented therapy, especially for a child who is an in- dependent ambulator. As children reach a gait functional plateau, usually between 5 to 7 years of age but sometimes as early as 4 years of age, a full analysis and evaluation 7. Al- though there was no history of birth problems, she had a workup with a brain MRI that was normal, and a diag- nosis of diplegic CP was made. She was placed in an AFO and her mother was encouraged to have her move using heavy push toys. By age 2 years, she was walking inde- pendently and by age 3 years, she was walking on her toes, going faster but falling a lot. She was wearing an articulated AFO and was in physical therapy where she had good continued improvement up to age 4 years. Therefore, she was continued for another year in the same program. By age 5 years, both her mother and therapist who were working with her felt that there had been little additional progress in the past 6 months. At this time, her physical examination demonstrated a popliteal angle of 50°, knee extended ankle dorsiflexion of 5°, and bilateral and knee flexed ankle dorsiflexion of 15°. Internal rota- tion of the hips was 70° with external rotation of 20°. Kinematics demon- strated increased knee flexion at foot contact, premature ankle dorsiflexion, and internal rotation of the hips (Fig- ure C7. The gastrocnemius had 2+ spasticity and the hamstrings and hip adductors had 1+ spasticity. Her mother was given the option to have either a dorsal rhi- zotomy or orthopaedic surgery, and she chose to do the orthopaedic procedures.
If we become less efficient in converting energy from fuel oxidation into ATP order suhagra 100mg free shipping erectile dysfunction gene therapy treatment, or if we use an additional amount of ATP for muscular contraction cheap 100 mg suhagra visa impotence vacuum device, we will oxidize an additional amount of fuel to maintain ATP homeostasis (constant cellu- lar ATP levels). With the oxidation of additional fuel, we release additional heat. Thus, heat production is a natural consequence of “burning fuel. Teefore has increased thyroid Thermogenesis refers to energy expended for the purpose of generating heat in hormone levels that increase his addition to that expended for ATP production. To maintain our body at 37 C, despite rate of ATP utilization and fuel oxi- changes in environmental temperature, it is necessary to regulate fuel oxidation and dation. An excess of thyroid hormones also its efficiency (as well as heat dissipation). In shivering thermogenesis, we respond may affect the efficiency of ATP production, to sudden cold with asynchronous muscle contractions (shivers) that increase ATP resulting in fewer ATP produced for a given utilization and, therefore, fuel oxidation and the release of energy as heat. The increased rate of ATP shivering thermogenesis (adaptive thermogenesis), the efficiency of converting utilization and diminished efficiency stimu- energy from fuel oxidation into ATP is decreased. More fuel needs to be oxidized lates oxidative metabolism, resulting in a to maintain constant ATP levels and, thus, more heat is generated. The hyperthyroid patient, therefore, complains of constantly feeling hot (heat intolerance) V. They are used principally to gen- erate ATP in oxidative phosphorylation. However, fuel oxidation also generates NADPH, which is most often used directly in energy-requiring processes. Carbo- hydrates also may be used to generate ATP through a nonoxidative pathway, called anaerobic glycolysis. Energy Transfer from Fuels through Oxidative Phosphorylation Fuel oxidation is our major source of ATP and our major means of transferring energy from the chemical bonds of the fuels to cellular energy-requiring processes. The amount of energy available from a fuel is equivalent to the amount of heat that is generated when a fuel is burned. To conserve this energy for the generation of ATP, the process of cellular respiration transforms the energy from the chemical bonds of fuels into the reduction state of electron-accepting coenzymes, NAD and FAD (circle 1, Fig. As these compounds transfer electrons to O in the elec- Oxidation is the loss of electrons, 2 tron transport chain, most of this energy is transformed into an electrochemical gra- and reduction is the gain of elec- trons. Remember LEO GER: dient across the inner mitochondrial membrane (circle 2, Fig. Much of the Loss of Electrons Oxidation; energy in the electrochemical gradient is used to regenerate ATP from ADP in Gain of Electrons Reduction. Compounds are oxidized in the body in essentially three ways: (1) the transfer of 1. OXIDATION-REDUCTION REACTIONS electrons from the compound as a hydrogen Oxidation-reduction reactions always involve a pair of chemicals: an electron atom or a hydride ion, (2) the direct addition donor, which is oxidized in the reactions, and an electron acceptor, which is reduced of oxygen from O2, and (3) the direct dona- tion of electrons (e. In fuel metabolism, the fuel donates electrons, and is oxidized, and Chapter 5). Fuel oxidation involves the trans- NAD and FAD accept electrons, and are reduced. In oxidation reactions, NAD accepts two electrons as a hydride ion to the oxidized compounds. Consequently, form NADH, and a proton (H ) is released into the medium (Fig 19. It is generally aldehydes are more reduced than acids, and used for metabolic reactions involving oxidation of alcohols and aldehydes. In contrast, alcohols are more reduced than aldehydes. Overview of energy transformations in oxidative phosphorylation.
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