Properties Of Enzymes Involved In Steroid Metabolism

Hydroxylation reactions play an important role in the metabolic pathways of many steroids, both those producing hormones as well as those generating bile acids. The cleavage of the cholesterol side chain necessitates the hydroxylation of both carbon-22 and carbon-20, while the production of testosterone necessitates hydroxylation of progesterone at carbon-17 followed by cleavage of the carbon-17-carbon-20 bond. In the biosynthesis of Cortisol, three hydroxylases, the 17a-, the 21-, and the 11...

Thyroid Hormone Binding Site

FIGURE 6-11 Model of thyroxine-binding prealbumin (TBPA). The schematic model is derived from X-ray crystallographic studies of prealbumin, illustrating the interaction of four identical subunits forming a channel through the interior of the molecule, thereby forming two identical thyroid hormone-binding sites. The channel narrows at the center of the molecule. Although the binding sites are identical, T4 binds cooperatively occupation of T4 at one site presumably alters the conformation of the...

Glucocorticoid Receptor

The glucocorticoid receptor is a member of the nuclear steroid-thyroid receptor gene gamily (Chapter 1). Like the other receptors in this superfamily, the glucocorticoid receptor can be divided into functional domains (Figure 1-26). The major functional regions consist of the ligand-binding domain (C-terminal), the DNA-binding domain (central), and the antigenic domain (N-terminal). Bars in the figure locate additional functions, including transactivation and dimerization. The glucocorticoid...

Prl

In humans, a-MSH is probably released from pars intermedia-like cells under the positive action of dopamine, not CRH. In these cells, the ACTH moiety is further broken down to a-MSH and CLIP, and these hormones are secreted together with 3-endorphin (breakdown product of 8-lipotropin). h These activities may derive from the neurointermediate lobe (at least in higher animals). PRF (a polypeptide of MW less than 5000) does not appear to be oxytocin, AVP, or 3-END) however, PIF could be related...

Clinical Aspects

Most inferences concerning pineal hormones and diseases have come from studies with experimental animals. Thus, pinealectomy at an early time in development in some species can lead to premature ovarian function, and treatment with melatonin can suppress ovarian function. As described earlier, the amounts of melatonin secreted nocturnally decline just prior to and during pubescence. Moreover, an acute oral dose (1-3 mg kg) given to young adults causes prolactin to be secreted. A number of...

Epidermal Growth Factor Egf Family

This growth factor is part of a family of growth factors that includes, besides EGF, TGF-a, amphi-regulin, heparin-binding EGF, and cripto. The linear FIGURE 19-2 Structure of single-transmembrane-segment receptors that form homologous dimers the growth hormone receptor. One GH molecule binds to identical binding sites on the extracellular domains of two GH receptors that form a homodimer. The intracellular domains associate with a tyrosine kinase of the Janus family of kinases. An encircled P...

Info

A Adapted with the permission of the authors and publisher from Wahren, J. (1979). Metabolic adaptation to physical exercise in man. In Endocrinology (L. J. DeGroot et al., eds.), Vol. 3., p. 1912. Grune & Stratton, New York. a Adapted with the permission of the authors and publisher from Wahren, J. (1979). Metabolic adaptation to physical exercise in man. In Endocrinology (L. J. DeGroot et al., eds.), Vol. 3., p. 1912. Grune & Stratton, New York. TABLE 7-4 Calorie Yield of Food...

F PGs and the Pain Mechanism

The pain mechanism is essential for survival, since acute pain is a warning mechanism for threatening conditions. Chronic pain is a more complicated subject, but both conditions may be grouped together for the purposes of our discussion. Relatively little is known about the pain mechanism. The nociceptors, when excited by potentially harm figure 16-12 Schematic diagram of the three-dimensional structure of soybean lipoxygenase-1. The a-helices are represented by cylinders, the strands in the...

Elfpplflevf Edqev 410

Figure 6-19 Schematic model of the structural domains of the thyroid receptor as determined via X-ray crystallographic techniques. The ligand binding domain of the thyroid receptor is composed of 255 amino acids which represent residues 156-410 in the intact thyroid receptor. This figure illustrates the 12 a-helices, designated Hi to Hi2 and the 4 3-strands, designated S, to S4 which comprise the secondary structure. The amino acid residues at the beginning and at the end of each a-helix are...

B LT and Asthma

Asthma is a complex disease resulting in part from narrowing of the airways. Mediators having various roles in this syndrome are derived from mast cells in the bronchus. These mediators act either directly on airway tissues or by indirect mechanisms, which in clude recruitment of inflammatory cells. Some mediators are preformed within the mast cell, whereas others are generated from the plasma membrane. The latter category includes the LTs, which may play a substantial role in asthma. The two...

General Comments

The pineal (so named for its pinecone shape) gland is rather unique with respect to the magnitude of change characterizing its evolutionary development. In amphibians it is primarily a photoreceptive organ, but in higher forms it has evolved from this state to a gland producing hormones that receives light information by way of the lateral eyes and sympathetic nerves. Pineal products include melatonin, other methoxyin-doles, serotonin, and acetylserotonin (see Figure 18-1). Although vasotocin...

Biosynthesis Of Hormones

The biosynthesis of all hormones largely occurs in specialized cells usually present in endocrine glands, which have the genetic phenotype to permit the correct orderly production of the hormone in question. Chapter 2 describes the production of the steroid hormones, while Chapters 6,11, and 16 describe the biosynthesis of the thyroid hormones, epinephrine, and prostaglandins, respectively. The next section of this chapter will provide a general description of the biosynthesis of peptide and...

Ho

FIGURE 5-31 Structures of the opiate receptor antagonist, naloxone, and the opiate receptor agonist, morphine. binding site. A summary of the properties of opioid receptors is presented in Table 5-4. Some general remarks can be made about opioid receptors. -Receptors may mediate most opioid analgesic effects, although some negative effects are listed in Table 5-4. c-Receptors produce analgesia at the spinal level and do not contribute to (drug) dependence. S-Receptors are important to the...

Srrapqtgi

FIGURE 5-28 Structure of human IGF-I, IGF-II, and insulin (ins), with amino acid residues aligned to show the homologies identified by the boxed areas. Single-letter codes are used for amino acid residues. Note that in insulin the C peptide is removed, whereas in IGF-I and IGF-II the A and B chains (domains) remain connected by the C peptide. In addition, there are D domains. Modified and reproduced, with permission, from Sara, Y. R., and Hall, K. (1990). Insulin-like growth factors and their...

Oncogenes

Genes for growth factors or their receptors PDGF Codes for platelet-derived growth factor. Involved in glioma ( a brain cancer) erb-B Codes for the receptor for epidermal growth factor. Involved in glioblastoma (a brain cancer) and breast cancer erb-B2 Also called HER-2 or neu. Codes for a growth factor receptor. Involved in breast, salivary gland and ovarian cancers RET Codes for a growth factor receptor. Involved in thyroid cancer Genes for cytoplasmic relays in stimulatory signaling pathways...

Apical Membrane Iodination Coupling Storage

FIGURE 6-4 Biosynthetic pathway for the production of thyroglobulin. TSH initiates the process via stimulation of the cAMP pathway. The mature mRNA is translated into the 2748-amino acid subunit of 330 kDa. The mature Tg is a dimer of two subunits. Before Tg is secreted, extensive glycosylation occurs. Modified with permission from Medeiros-Neto, G., Targovnik, H. M., and Vassart, G. (1993). Defective thyroglobulin synthesis and secretion causing goiter and hypothyroidism. Endocr. Rev. 14,...

Lyg

FIGURE 3-9 Metabolism of thyrotropin-releasing hormone (TRH). Reproduced from Fag-lia, G., and Persani, L. (1991). Thyrotropin-releasing hormone, basic and clinical aspects. In Brain Endocrinology (M. Motta, ed.), 2nd ed., pp. 315-350. GRH has been localized to the arcuate nucleus of the hypothalamus. CRH also appears to be located elsewhere, in addition to the hypothalamic-hypophyseal axis. It has been found in the central nucleus of the amygdala (of the limbic system) and in polar neurons and...

Biosynthesis Of Cholesterol

The most commonly occurring steroid is cholesterol (3). Cholesterol is present in practically all living organisms, including blue-green algae and bacteria. The levels of cholesterol in plant tissues are low, except in some pollen and seed oil. Animal products are rich sources of cholesterol cholesterol is present in high concentrations in the myelin sheath and in almost pure form in gallstones. Above-average levels can be found in skin, sperm cells, and egg yolk. Virtually all cell membranes...

References

L eds. (1990). Biological Rhythms, Mood Disorders, Light Therapy And The Pineal Gland. American Psychiatric Press, Inc., Washington, DC. Wurtman, R. J. (1980). Neuroendocrinology (D. T. Krieger and . C. Hughes, eds.). Sinauer Associates, Sunderland, MA. Arendt, J. (1995). The pineal gland basic physiology and clinical implications. Endocrinology (L. J. DeGroot, ed.) 1, 432-444. Dubocovich, M. L. (1995). Melatonin receptors are there multiple subtypes Trends Pharmacol....

G

The genetic code is expressed in terms of triplet sequences as they would appear in a natural messenger RNA molecule. The sequence of each codon is read from left to right, starting with the 5' end and going toward the 3' end. The codons UAA, UAG, and UGA are stop signals that result in chain termination and are used to indicate the end of a polypeptide chain. No separate codon is required to start the polypeptide chain, since the first amino acid is always methionine (Met).

Development

The human pineal gland starts as an evagination of the roof of the third ventricle in the second month of gestation. The pineal anlage, the ependyna, a lobular structure, fuses into a solid and becomes invested with vascular connective tissue, giving a lobular appearance to the pineal parenchyma. The pineal gland then changes from a vertical to a horizontal organ and becomes innervated. In neonates, the pineal is shown to consist of two cell types, type I and type II. Type I cells

Melatonin Receptor

Specific melatonin-binding sites have been defined by using 2-125I iodomelatonin as a radioactive ligand. High-affinity sites have been found in suprachiasmic nuclei and pars tuberalis. The levels of the melatonin receptor(s) in these structures are inversely related to the plasma concentration of melatonin. Consequently, the level of melatonin receptors is increased during the day. The light-dark cycle appears to be the regulatory factor. The density of melatonin receptors decreases during the...

Apw

In both locations, the biological response generated by angiotensin II is mediated as a consequence of its binding to high-affinity membrane receptors these receptors have been cloned and found to have a seven transmembrane domain that is linked to a G protein (see Chapter 1). The immediate postangiotensin II receptor-binding signal transduction events include the elevation of both IP3 and intracellular Ca2+ concentrations. The site of production of the...

Thymopoietin

Three distinct thymopoietins have been characterized that are splice variants involving similar N-termini, but different C-termini with molecular weights of 75,51, and 39 kDa. mRNAs are expressed in various tissues but are most abundant in adult thymus and fetal liver. These proteins may have unique functions and have subcellular locations in different compartments. It is of interest that expression of human myotonin protein kinase cDNA in COS cells encodes a protein with a thymopoietin-like...

Anatomical And Morphological Relationships

Figure 6-1 shows the location and structure in humans of the thyroid gland. In adults the thyroid gland weighs 10-20 g. It consists of brownish-red right and left pear-shaped lobes. The two lobes are connected by an isthmus and lie on the lower part of the larynx and the upper part of the trachea. From the inner capsule of the thyroid, septa extend into the gland, dividing it into lobules of varying shape and size. The separate lobules are composed of follicles, which are the

Biological And Molecular Actions

Role of VP (Antidiuretic Hormone) in the Regulation of Body Fluids The primary action of arginine vasopressin (AVP) is in the inhibition of water diuresis (loss of water in the urine), and this action operates through the actions of membrane receptors in the kidney. AVP also elevates blood pressure and constricts coronary arteries, and it stimulates intestinal and uterine contractions, as well as slightly stimulating milk ejection. However, the last two activities modestly cross over to the...

Thrombincollagenepinephrine

FIGURE 16-21 Interrelationships between platelet cell membrane stimulators (thrombin, collagen, epinephrine), TX (TXA), Ca2+, PGI and adenylate cyclase. FIGURE 16-21 Interrelationships between platelet cell membrane stimulators (thrombin, collagen, epinephrine), TX (TXA), Ca2+, PGI and adenylate cyclase. FIGURE 16-22 Mast cell-derived pharmacological mediators of hypersensitivity. Reproduced from Kay, A. B. (1982). Eur. J. Respir. Dis. 63 (Suppl. 122), 9-16. Copyright 1982 Munksgaard...

Adrenal

Figure 14-9 Pathways and anatomical compartmentalization of the production of the C-21 progestins, particularly progesterone, 17a-hydroxyprogesterone, and 16a -hydroxyproges-terone in the human fetal placental unit. This figure was derived in part from Buster, J. E., and Marshall, J. R. (1979). Conception, gamete and ovum transport, implantation, fetal placental hormones, hormonal preparation for parturition and parturition control. In Endocrinology (L. J. DeGroot, G. F. Cahill, L. Martini, D....

N

Naloxone, 160 Nephrons counter-current exchange, 418-419 in kidney, 415, 417 Nerve endings, 92, 95 Nerve growth factor, 506, 508-509, 511 factors, 506 receptors, 506, 508-510 signal transduction, 509, 511 Neurokinin B, 241, 244 Neurons, 91-95, 114, 117 Neuropeptide Y, pregnancy, 394-395 Neurophysins, active sites, interaction with posterior pituitary hormones, 112-116 Neurosecretory granules, 326-327, 330-331 Neurotensin, 240 Neurotransmitters, 6-7, 231 Nicotinic acetylcholine receptor, 324-325...

Thyroid Gland

FIGURE 6-1 Location and structure of thyroid gland in humans. main structural and functional units of the thyroid parenchyma. In the human thyroid gland there are 20-30 million follicles. The thyroid gland has a rich blood supply, with each lobe being serviced by three arteries. The blood flow to the thyroid gland is 5 ml g min. The thyroid tissues comprise two principal cell types the follicle cell (see the following paragraph) and parafollicular cells or C cells. The C cells are found in the...

Biochemistry

Location of Releasing Hormones in the Central Nervous System The location of the releasing hormones in various cells of the CNS has been accomplished frequently by the use of fluorescently labeled monospecific antibodies and microscopic detection of fluorescence. The localization of TRH by this method is to the nerve terminals of the hypothalamic nuclei of the dorsomedial nucleus, the paraventricular nucleus, and the periforni-cal region. There are some other locations for TRH outside of the...

S

FIGURE 16-1 General features of major classes of PG relatives. A and B represent hydroxyl or ketone substituents. LT and LP are fatty acid derivatives. LT contains glutathione. FIGURE 16-1 General features of major classes of PG relatives. A and B represent hydroxyl or ketone substituents. LT and LP are fatty acid derivatives. LT contains glutathione. general structures mentioned here are shown in Figure 16-1.

Ergocalciferol

FIGURE 9-5 Structural relationship of vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol) with their respective provitamins, cholesterol, and a classic steroid hormone, Cortisol (see inset box). The two structural representations presented at the bottom for both vitamin D3 and vitamin D2 are equivalent, these are simply different ways of drawing the same molecule. It is to be emphasized that vitamin D3 is the naturally occurring form of the vitamin it is produced from...

Detail Of Liver Lobule

FIGURE 10-5 Anatomical components of the liver and hepatocyte, a major target cell for glucocorticoids. This drawing was made originally by Dr. Laurie Paavola, Department of Anatomy, Temple Medical School, and is redrawn here with her permission. Other work with a polyclonal antibody to the glucocorticoid receptor indicates that the hepatocyte is the cell in the liver having a large number of receptor antigens, while the bile and Kupffer cells have little or no antigenic activity. amounts of...

Growth Hormone Gh And Somatomedins Igfs

Although this subject overlaps that of Chapter 5 on anterior pituitary hormones, it is a reasonable starting point since IGF-I is a major growth factor. The relationship between growth hormone and IGF-I is shown in Figure 19-1. Here it is shown that GH is released through the action of hypothalamic growth hormone-releasing hormone (GRH), as described earlier in Chapter 3. The GH released into circulation has two effects One effect is to directly act on lipid and fat metabolism, analogously to...

Mechanism Of Hormonal Action

Most peptide hormones do not require entry into the cytoplasm of their target cells to initiate a biological response since the ligand-binding domain of the receptor exists on the outer surface of the target cell (see Figure 1-22). As discussed in relation to Figure 1-20, some peptide hormones (e.g., insulin and nerve growth factor), when bound to their receptor, are subjected to endocytosis and are moved into the interior of the cell. As discussed in Chapter 2, most steroid hormones have...

Anpr B

FIGURE 15-10 Structural organization of atrial natriuretic peptides and their receptors. (A) Structural homology of the A, B, and C types of human ANP. In the 17-membered ring, amino acids that are identical are shown as open circles. Abbreviations ANP, atrial natriuretic peptide BNP, brain natriuretic peptide CNP, C-type natriuretic peptide. Modified with permission from Sudoh et al. (1990). (B) Schematic representation of receptor classes for human ANP. Note The terminology for designation of...

Male Sex Differentiation

FIGURE 14-15 Schematic diagram of male and female sex determination and differentiation. The key contribution of the SRY gene or testis-determining factor is emphasized on the right for the male see also Figures 14-17 and 14-18 for additional details. Modified from Grumbach, M. M. (1967). Biologic Basis of Pediatric Practice (R. E. Cooke, ed.), p. 1060. McGraw-Hill, New York. In the absence of the SRY gene, female sex differentiation will lead to conversion of the indifferent gonad anlage into...

Antihypertensive Renal Effects

In response to some stimuli (e.g., fright), catecholamines are secreted, causing renin to be released from the kidney juxtaglomerular apparatus. Renin stimulates the production of angiotensin II (Figure 15-7), and blood pressure elevation ensues from enhanced aldosterone production, Na+ reabsorption, and constrictive effects on the vasculature. In response to the increased pressure, there is increased blood flow in the renal medulla, resulting in the release of PGA2 or PGE2 (see Chapter 15)....

Clinically Relevant Endocrine Disorders1

Addison's disease Bartter's syndrome Cushing's disease Cushing's syndrome Diabetes insipidus Diabetes mellitus Diabetes mellitus (insulin-dependent or type I diabetes) Diabetes mellitus (insulin-independent or type II diabetes) Inappropriate and continued secretion of growth hormone by a tumor of pituitary cells which leads to soft tissue swelling and hypertrophy of the skeletal extremities (usually in the third or fourth decade). Adrenocortical insufficiency resulting from a deficient...

Chondrocyte

MOBILIZATION ACCRETION OF Ca2* & Pi FIGURE 9-8 Summary of the vitamin D endocrine system. In addition to production of lct,25(OH)2D3 and 24R,25(OH)2D3 by the endocrine gland function of the kidney, small amounts of la,25(OH)2D3 are also produced in a paracrine fashion and by the placenta during pregnancy. Target organs and cells for la,25(OH)2D3 by definition contain nuclear receptors for lc*,25(OH)2D3 (nVDR). Also, la,25(OH)2D3 generates biological effects involving rapid signal...

Chemistry

A major hormone secreted by the pinealocyte is melatonin, shown in Figure 18-1. Serotonin and N-acetylse-rotonin also are important in the pineal, but they may not be secreted. Both melatonin and serotonin are derived from tryptophan, with the characteristic feature of all of these compounds being the indole ring (Figure 18-1). Other hydroxy- and methoxyindoles are present in the pinealocyte, as will be evident from the discussion of the biochemistry. The pinealocyte may secrete a peptide,...

Mammals

FIGURE 18-3 Vertebrate pineal cells showing evolution from a photoreceptor cell to a pinealocyte. Diagram of typical vertebrate pineal cells. Abbreviations PC, photoreceptor cell RPC, rudimentary photoreceptor cell PI, pinealocyte. Reproduced from Hansen J. T., and Karasek, M., (1982). Neuron or endocrine cell The pinealocyte as a paraneuron. In The pineal and its hormones (R. J. Reiter, ed.), pp. 1-9. Alan R. Liss, Inc., New York. predominate at birth, are often pigmented, and are positive for...

Tumor Suppressor Genes

APC Involved in colon and stomach cancers DPC4 Codes for a relay molecule in a signaling pathway that inhibits cell division. Involved in pancreatic cancer NF-1 Codes for a protein that inhibits a stimulatory (Ras) protein. Involved in neurofibroma and pheochromocytoma (cancers of the peripheral nervous system) and myeloid leukemia NF-2 Involved in meningioma and ependymoma (brain cancers) and schwannoma (affecting the wrapping around peripheral nerves) MTS1 Codes for the pl6 protein, a braking...

Ectopic Production Of Hormones By Tumor Cells

There are many examples of tumors producing hormones that are unrelated to the tissue of origin. This only underscores the dedifferentiated state of the cancer cell. Apparently there is no clear understanding of the reason for the production of a specific unexpected hormone by a given tumor cell, except that rearrangements of genes may occur and the rearranged gene may insert next to a highly expressing sequence and be overproduced. Thus, the term ectopic is used, which refers to the generation...

General Considerations of Hormones

OVERVIEW OF HORMONES, RECEPTORS, AND ENDOCRINOLOGY B. Classes of Hormone Molecules C. Classification of Hormonal Communication Systems D. General Concept of a Hormone Receptor E. Hormones and Cascade Systems B. Biosynthesis of Peptide and Protein Hormones C. Regulation of Hormone Secretion D. Measurement of Hormone-Receptor Interactions E. Regulation of Hormone Receptors IV. MECHANISM OF HORMONE ACTION A. Hormone Entry into Target Cells B. Receptor-Mediated Transmembrane Signaling C. Steroid...

Ru 486

FIGURE 10-30 Structure of RU-486 compared to progesterone, Cortisol and testosterone whose receptors are affected by RU-486. Protein metabolism Thinning of skin Reddish striae Loss of bone matrix and demineralization Capillary fragility and bruising Impaired growth (children) Carbohydrate metabolism Abnormal glucose tolerance curve Overt diabetes mellitus Centripetal fat distribution Moon face Eosinopenia, lymphopenia Polymorphonuclear leukocytosis Erythrocytosis a Cushing's syndrome is most...

Chemistry And Biochemistry

The structures of the principal steroid hormones of the adrenal cortex are shown in Figure 10-6. The chemistry and structural relationships of the glucocorticoids compared to the other steroid hormones are reviewed in Chapter 2. The metabolic pathway for the production of glucocorticoids is presented in Figure 2-22. Glucocorticoids are secreted in large amounts in humans, up to 25 mg or more per day, and represent a major chemical response of the body to stress. A person undergoing long-term...

Hypertension

Hypertension is a disorder that may occur throughout life it is defined as the continued elevation of blood pressure beyond defined limits (see Table 15-4). In adults the criterion of moderate hypertension is where the systolic and diastolic pressures exceed 160 and 100 mm Hg, respectively. As many as 50 million Americans have elevated blood pressure. Hypertension has a worldwide incidence of 9-18 in the adult population. In the presence of continuing uncontrolled hypertension, there is...

Anatomy And Cell Biology

In humans, the pineal gland is located in the brain grossly between the thalamus and the mesencephalon, as shown in Figure 18-4. In adults the pineal is a flat, cone-shaped structure with dimensions of about 58 mm long and 3-5 mm wide and weighing around 120 mg. It is located at the posterior border of the third ventricle above the roof of the diencephalon, being connected to it by a short stalk. The pineal is covered by a layer called the pia mater. From the pia mater, connective tissue septa...

Transforming Growth Factor Tgf3 Family

The crystal structure of TGF- 3 has been determined, and a computer model is shown in Figure 19-8. TGF- 3 either stimulates or inhibits cell growth or affects cellular functions distinct from mitosis. Among the activities of TGF- 3 are inhibition of proliferation of mesenchymal, epithelial, endothelial, and transformed cells, stimulation of proliferation of these cell types, control of extracellular matrix interactions, suppression of immune function, regulation of embryogenesis and cellular...

Chemistry Of Steroids

Steroids are derived from a phenanthrene ring structure (structure 4) to which a pentano ring has been attached this yields in the completely hydrogenated form, cyclopentanoperhydrophenanthrene, or the ster-ane ring structure (structure 6, Figure 2-2). Steroid structures are not normally written with all the carbon and hydrogen atoms as illustrated in 5 of Figure 2-2 instead, the shorthand notation as presented for sterane (6, Figure 2-2) is usually employed. In this representation the hydrogen...

Qrj

Figure 14-18 Model of the genetic bases for sexual differentiation illustrating the primordial role of the SRY gene and its protein product, which is functional only in the 46XY male. In this model, the Z gene could be equivalent to the cytochrome P450 aromatase gene described in Figure 14-17. In the absence of the SRY protein (a 46XX female), the enzymatic capability to convert testosterone to estradiol is operative, whereas in a 46XY male, the aromatase enzyme is not expressed, which thus...

Kib

FIGURE 6-10 Proposed mechanism for the coupling of two iodo-tyrosines to generate tyrosines. The entire coupling reaction is catalyzed by TPO as reaction 5 of phase B (see Fig. 6-9). The three concerted reactions are indicated. It is not clear whether TPO-mediated coupling occurs via an ionic or a free radical mechanism. Modified with permission from Gentile, F., DiLauro, R., and Salva-tore, G. (1995). Biosynthesis and secretion of thyroid hormones. In Endocrinology (L. J. DeGroot et ah, eds.),...

Tpo

FIGURE 6-7 Process of thyroid hormone biosynthesis and secretion by a thyroid follicular cell. Abbreviations IT, iodide transporter ER, endoplasmic reticulum GA, Golgi apparatus SG, secretory granules EV, exocytotic vesicles NO, NADPH oxidase TPO, thyroid peroxidase MV, microvilli (which are present all over the apical surface but have been omitted for clarity) MPV, micropinocytotic vesicles (involved in Tg reabsorption) PP, pseudopods CD, colloid droplets EE, early endosomes LE, late...

Cell Biology

The immune system as a whole may be visualized as consisting of two major components cellular and humoral immunity. Both respond to foreign proteins or other antigens. The y-globulin fraction of plasma antibodies constitutes the humoral mechanism, whereas cellular immunity refers to lymphocyte products (lymphokines, e.g., the interleukins). The humoral mechanism protects against bacterial infection, whereas cellular immunity generates delayed allergic reactions and rejections of foreign tissue...

Hormones of Pregnancy and Lactation

Sequence of Events in Reproduction II. ANATOMICAL AND MORPHOLOGICAL RELATIONSHIPS B. Fetal Placental-Decidual Unit III. CHEMISTRY, BIOCHEMISTRY, AND BIOLOGICAL RESPONSES IV. CELL BIOLOGY AND MOLECULAR ACTIONS A. Hormonal Aspects of Fertilization A. Pregnancy-Gestational Neoplasms B. Anomalies of Sex Determinants

Gastrointestinal Hormones

Resume of the Gastrointestinal Hormones C. Problems of Food Processing and Digestion II. ANATOMICAL, MORPHOLOGICAL, AND PHYSIOLOGICAL RELATIONSHIPS A. Gastroenteropancreatic System D. Hormone-Secreting Cells Their Distribution in the Gastroenteropancreatic Complex E. Coordination of Gastroenteropancreatic Hormone Release III. CHEMISTRY AND BIOCHEMISTRY J. Pancreatic Polypeptide Family (PP) K. Somatostatin L. Bombesin and Tachykinin Peptide Families M. Calcitonin Gene-Related Peptide N....

Water Balance

Osmoreceptors (Figure 4-10A) located in the hypothalamus (and also in the carotid artery) are capable of sensing increased concentrations of solutes, particularly Na+. This leads to a secretion of vasopressin, which stimulates renal tubular water reabsorption. At the same time, the thirst center in the hypothalamus, which is linked to the osmoreceptor, is stimulated with a concomitant increase in water consumption. 1. Renal Relationships of K+ and Na+ Although Na+ is the principal extracellular...

Iqy

FIGURE 13-20 Schematic models illustrating how steroid antagonists (antihormones) might block the formation of a competent ligand-receptor-mediated transcription complex. (A) In this model, a pure antagonist interferes with the nuclear-cytoplasmic shuttling process, with the result that the receptor accumulates in the cytoplasm and is degraded. Abbreviations HRE, hormone response element hsp 90, heat shock protein 90 AH, antihormone. (B) In this model, the key point is that an antihormone (AH)...

Classification of PGs

Although the many structures in this group of compounds may seem bewildering at first (Figure 16-2), there are some simple generalizations that can be set forth to allow a facile understanding of structure-function relationships. PGs arise from a cyclic endoperoxide generated by the enzyme system, PG synthetase. This is a complex of enzymes, including cyclooxygen-ase, required to produce the key intermediate, the cyclic endoperoxide derivative of arachidonic acid or other fatty acids. There is...

Daysqggsn

FIGURE 17-6 Sequences of thymic hormones. Abbreviations Ac, acetyl x, unknown B, Asp or Asn Z, Glu or Gin. Underlined sequence represents a nuclear translocation signal. t-cell system (cell mediated) transplant and tumor mmunity also viral, mycobacterial fungal and protozoal immunity b-cell system (antibodies) bacterial and viral immunity FIGURE 17-7 Hypothetical model illustrating the major interactions between the central nervous system and the neuroendocrine thymus. From Goldstein, A. L.,...

Compilation of Most Known Hormones in Higher Mammals and Humans

Amino acid-derived hormones Adrenals Bursa of Fabricius (chickens) Bursin Dopamine (also belived to be PIF) y-Aminobutyric acid GABA Octopamine Thyroid parathyroid gland Thyroxine (T4) and triiodothyrone (T3) Autoimmune antibodies acting like unregulated hormones Autoimmune anti-insulin Long-acting thyroid stimulator LATS

Pga

Lee, in Principles of Endocrinology (R. H. Williams, ed.) 5th ed., p 855. Saunders, Philadelphia, Pennsylvania, 1975. series (PGA) is the least polar or hydrophilic, is the most lipophilic, and has no hydroxyl groups substituted on the five-membered ring, but rather a ketone group and an unsaturation (Table 16-1). These classes of PGs have characteristic actions depending on the five-membered-ring substituents, as shown in Table 16-1. Inspection of Table 16-1...

Aaaa

FIGURE 7-17 Synopsis of the regulation of expression of the insulin gene. The primary transcription of the insulin gene is selectively stimulated by elevated cAMP and or glucose. In addition, insulin mRNA levels are stabilized at high glucose levels, which also selectively stimulates the translation of insulin mRNA at the levels of initiation, elongation, and interaction of signal recognition particles (SRP) with a docking protein (DP) Modified with permission from Steiner, D. F., Bell, G. I.,...

Hormone Receptor Status Of Breast Cancers

Breast cancer is diagnosed at a level of about 100,000-120,000 new cases per year in the United States, and 40,000 die each year from this most common cause of cancer in women. For some time breast cancers have been classified on the basis of receptor measurements from biopsy specimens. Thus, in general, these cancers fall into three categories estrogen receptor (ER) positive and progesterone receptor (PR) positive ER positive and PR negative and ER negative and PR negative. These measurements...

P Q

FIGURE 7-7 Primary amino acid sequences of human and hagfish insulins. In addition, the amino acid sequences of 70 other vertebrate insulins are known, and the substitutions that occur at each position (indicated as other) are shown for comparison. The invariant residues are enclosed in boxes. Reproduced with permission from Steiner, D. F. Bell, G. I., Tager, H. S. and Rubenstein, A. H. (1995). Chemistry and biosynthesis of the islet hormones Insulin, islet amyloid polypeptide (amylin),...

Growth Hormone

The sequence of human GH is given in Figure 5-3. Human GH is a peptide containing two disulfide bonds with a molecular weight of 22,000, although a smaller variant of 20,000 accounts for about 10 of GH and lacks amino acids 32-46 through processing of the GH mRNA precursor. A large form of GH is represented by a dimer stabilized by an interchain disulfide bond, and larger forms have been described. The forms larger than 22,000 probably are not physiologically important. A glycosylated form of...

A I B I

Pregnan-3 3-ol (20) Pregnan-3a-ol (21) Pregnan-3 3-ol (20) Pregnan-3a-ol (21) FIGURE 2-4 Structural consequences resulting from the reduction of pregnan-3-one. The orientations of a- and 3-hydroxyls of compounds 20 and 21 as equatorial (e) or axial (a) substituents, respectively, on the chair version of the A rings are shown in the bottom row. FIGURE 2-4 Structural consequences resulting from the reduction of pregnan-3-one. The orientations of a- and 3-hydroxyls of compounds 20 and 21 as...

Relation Of Some Hormones To Carcinogens And Development Of Cancer From Inappropriate Hormonal Treatment

Some time ago it was recognized that certain well-known carcinogenic substances structurally resembled steroid hormones. These carcinogens had been shown to produce tumors in experimental animals. In this context, the structures of benzo a pyrene and 7,12-dimethylbenz anthracene can be compared to the structure of estradiol (Figure 20-1). The structural similarities are even more apparent when the molecules are aligned and overlaid as shown in Figure 20-2. It thus is not surprising that steroid...

Y E V

FIGURE 1-42 Zinc finger motifs present in hormone response elements of steroid receptors. (A) Generic representation of a Zn+ finger. A highly schematic model for the general conformation of the DNA-binding domain is shown with each amino acid represented by a sphere the polypeptide chain in each finger is actually thought to be folded into a complex globular conformation. (B) Schematic view of how four such zinc fingers might bind to a specific DNA sequence. Each zinc finger is postulated to...

Preface to the First Edition

The past decades have brought startling advances in our understanding of endocrinology. Of paramount importance is the large increase in the number of legitimate hormones, which now number more than 100, as well as the application of the modern concepts and methodologies of biochemistry and molecular biology to endocrinological research. It is now feasible to approach virtually all classical topics in endocrinology at the cellular and molecular levels. This book provides a comprehensive...

O X

Hyperparathyroidism Hypoparathyroidism Pseudohypoparathyroidism Secondary hyperparathyroidism Cirrhosis Drug induced metabolism Obstructive jaundice Hypophosphatemic VDRR Vitamin D-dependent rickets FIGURE 9-16 Human disease states related to vitamin D. principal daughter metabolites la,25 OH 2D3 and 24,25 OH 2D3 3 conditions that may be due to variations in organ responsiveness to these dihydroxylated metabolites and 4 perturbations in the integrated interactions of these metabolites with PTH...

Ch3o

Follows increases in glycogenolysis and gluconeogene-sis in the liver, increased gluconeogenesis in skeletal muscle, increased inotropic effect affecting the force of muscular contraction in the heart , increased amylase secretion by the salivary gland, relaxation of the uterine musculature, conversion of triglycerides to free fatty acids and glycerol in adipose, elevations in blood pressure, heart rate, and cardiac output depending on amount of catecholamine , and dilation of bronchial...

Thyrotropic Hormone

Nerve Growth Factor Ngf Pathway

Like other polypeptide hormone receptors, TSH receptor is located in the cellular membrane of thyroid cells. A functional model of the TSH receptor has been hypothesized and is shown in Figure 5-35. TSHR is a seven-membrane-spanning domain receptor with a large extracellular domain. TSH binding is in the extracellular domain, and trypsinization of cells containing the receptor generates a 15-30-kDa peptide capable of binding TSH. Apparently the loops themselves are not involved in ligand...

Nerve Growth Factor

Growth Hormone And Ngf

NGF was discovered in the mouse submaxillary gland. It has a molecular weight of 13,259 and exists in a complex of 140 kDa. The complex contains two molecules of NGF 3-subunits together with two a-and two y-subunits the y-subunit is arginine esterase . Apparently the identity of the a-subunits remains unclear. Although NGF is not a mitogen, it prevents apop-tosis of neurons. A now classical demonstration of the induction of apoptosis is the withdrawal of NGF, usually in chick embryos, that...

Aldosterone Receptor

Like the glucocorticoid receptor, the mineralocorti-coid receptor resides in the cytoplasm in the unoccupied by ligand form and also appears to contain hsp 90 in a heteromeric structure. Different from the glucocorticoid receptor, it appears that aldosterone binds in the binding pocket of the mineralocorticoid receptor D ring first, as contrasted with A ring first in the case of the glucocorticoid receptor Figure 10-28 . In addition, there seem to be three possible configurations of...

Cortical collecting duct cell

FIGURE 15-9 Cellular model of the actions of aldosterone on Na and K transport processes in the mucosal cells of the collecting duct of the kidney. In the absence of aldosterone, there is only basal update of Na from the lumen by the Na permease and a basal rate of translocation of the Na across the cell so as to exit the peritubular side of the cell via the action of a Na K ATPase. The figure illustrates the five steps which are believed to be operative in the presence of aldosterone. Step J ,...

Anatomical And Morphological Relationships Of The Male Reproductive System

Testicular Lobule

The male reproductive system comprises the gonads two testes , excretory ducts epididymis, vas deferens, and ejaculatory duct , and several accessory structures prostate, seminal vesicles, bulbourethral glands, and penis . These are illustrated in Figure 12-1. The key steps of organogenesis of the sexually indifferent, yet chromosomally determined male gonad are discussed in Chapter 14. The presentation of this chapter will begin with the generation of the morphologically identifiable testes....

Actions of Melatonin on Anterior Pituitary

Melatonin Comes From Anterior Pituitary

Melatonin inhibits the secretion of LH and FSH induced by GnRH. In particular, this has been demonstrated with anterior pituitary cells obtained from 1-to 20-day-old rats. The inhibition by melatonin was effective in the range 0.1-1.0 nM when the cells were obtained from animals that were 5, 10, or 15 days of age. Suppression of anterior pituitary hormone release ranged to 50 of the full response to GnRH, as shown in Figure 18-11. Melatonin interferes either with the GnRH stimulation of...

A ring contacts

FIGURE 10-27 Completed predicted structure of the GR HBD family, based on an alignment with thermitase, in crossed stereo. The original structure is in color, therefore some details are not obvious. Locations of contacts and point of entry of the steroid molecule are indicated by the current authors of HORMONES. The model is reproduced by permission from Goldstein, R. A., Katzenellenbogen, J. A., Luthey-Schulten, Z. A., Seielstad, D. A., and Wolynes, P. G. 1993 . Three-dimensional model for the...

Xl Acth Receptor

Skin Rash And Adrenal Insufficiency

The ACTH receptor has now been cloned from several sources, including bovine and human. The bovine receptor has 297 amino acid residues deduced from the DNA and a molecular weight equivalent of about 33,260. It is a seven-membrane-spanning domain receptor. It is reported to have glycosylations in the N-terminus. The receptor appears to have phosphorylation sites for protein kinases A and C, and the consequent participation of these kinases in ACTH FIGURE 5-37 Model of TSHR with the TSH site and...

Hormone Action And Biochemistry

Preganglionic Neuron

Biochemistry of the Chromaffin Cell of the Adrenal Medulla The relationship of the adrenal cortex to the medulla is shown in Figure 11-4. In Figure 11-4A, the vascular relationships are evident. The secretions from the cortex bathe the medulla on their way to the general circulation. Since unique environmental signals similar to those that cause epinephrine secretion from the medulla also stimulate glucocorticoid synthesis in the cortex, a ready supply of Cortisol is available to the medulla...

Gonadotropic Hormones Lh And

Characteristics and actions of LH and FSH are discussed in Chapter 13 however, brief space will be given to a discussion here. Structural considerations have also been discussed. There are similarities between LH, FSH, CG, and TSH, all of which contain an identical a-subunit. FSH and LH bind to membrane receptors in their target cells and couple to G proteins through conformational changes in ligand-receptor structures that avail specific sequences in the bound a-subunit similar to AVP arginine...

Anatomical And Morphological Relationships Of The Female Reproductive System

Corpus Hemorrhagicum

The human female reproductive system comprises the gonads two ovaries and uterine tubes, a single uterus, a vagina, external genitalia, and the mammary glands. These are diagrammed in Figure 13-1 with the exception of the mammary glands, which are diagrammed in Figure 14-5. The key steps of organogenesis of the sexually indifferent, yet chromosomally determined female gonad are discussed in Chapter 14. The presentation in this chapter will begin with the generation of a morphologically...

Division H Of Meiosis

Annulate Lamellae

Figure 13-3 Meiotic processses in germ cells in women as related to their age and sexual development. Modified from Odell, W. D. 1979 . The reproductive system in women. In Endocrinology L. J. DeGroot, G. F. Cahill, L. Martini, D. H. Nelson, W. D. Odell, J. T. Potts, Jr., E. Steinberger, and A. I. Winegard, eds. , Vol. 3, p. 1385. Grune amp Stratton, New York. Ovulation of a single ovum each month requires only about a total of 400 oogonia over the 30-40 year period of reproductive fertility....

RVhpid droplets V

Diagram Spermatozoa

7-. .r gt gt i i figure 12-9 Cellular organization of cells of the seminiferous tubules of a human testis. Leydig cells occur in clusters surrounded by several seminiferous tubules as well as capillaries. Reproduced with permission from Christensen, A. K. 1975 . Leydig cells. In Handbook of Physiology D. W. Hamilton and R. O. Greep, eds. , Section 7, Vol. V, pp. 57-94. Williams amp Wilkins, Baltimore, MD. important functions 1 production of unique proteins, including androgen-binding protein...

Modifying Aminergic And Peptidergic Hormones

Neuroendocrinology

FIGURE 5-1 Overview of the anterior pituitary hormones showing the connections between the aminergic hormones and neurotransmitters of the CNS, the releasing hormones from the hypothalamus, and the anterior pituitary hormones together with the organs upon which they act and their general effects. GRH, Growth hormone releasing hormone, or somatocrinin GIH, growth hormone release-inhibiting hormone, or somatostatin TRH, thyroid-stimulating hormone releasing hormone CRH, corticotropic releasing...

Hi

M2 muscarinic acetylcholine m3 muscarinic acetylcholine m 1 muscarinic acetylcholine m4 muscarinic acetylcholine D2 dopamine D3 dopamine D4 dopamine octopamine RDC4 02b-adrenergic adenosine A1 adenosine A2 serotonin lc serotonin 2 fij-adrenergic D1 dopamine rat cannabinoid human cannabinoid adrenocorticotropin melanotropin neurokinin a substance K neuromedin K rhodopsin endothelin A endothelin B I bombesin neuromedin B f-metleuphe vasoactive intestinal peptide bradykinin gt angiotensin II C5a...