Showing papers in "Endocrine Reviews in 1997"

The biology of vascular endothelial growth factor

Abstract: The establishment of a vascular supply is required for organ development and differentiation as well as for tissue repair and reproductive functions in the adult1 Neovascularization (angiogenesis) is also implicated in the pathogenesis of a number of disorders These include: proliferative retinopathies, age-related macular degeneration, tumors, rheumatoid arthritis, and psoriasis1,2 A strong correlation has been noted between density of microvessels in primary breast cancers and their nodal metastases and patient survival3 Similarly, a correlation has been reported between vascularity and invasive behavior in several other tumors4–6

Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis.

Abstract: It is now clear that PCOS is often associated with profound insulin resistance as well as with defects in insulin secretion. These abnormalities, together with obesity, explain the substantially increased prevalence of glucose intolerance in PCOS. Moreover, since PCOS is an extremely common disorder, PCOS-related insulin resistance is an important cause of NIDDM in women (Table 3). The insulin resistance in at least 50% of PCOS women appears to be related to excessive serine phosphorylation of the insulin receptor. A factor extrinsic to the insulin receptor, presumably a serine/threonine kinase, causes this abnormality and is an example of an important new mechanism for human insulin resistance related to factors controlling insulin receptor signaling. Serine phosphorylation appears to modulate the activity of the key regulatory enzyme of androgen biosynthesis, P450c17. It is thus possible that a single defect produces both the insulin resistance and the hyperandrogenism in some PCOS women (Fig. 19). Recent studies strongly suggest that insulin is acting through its own receptor (rather than the IGF-I receptor) in PCOS to augment not only ovarian and adrenal steroidogenesis but also pituitary LH release. Indeed, the defect in insulin action appears to be selective, affecting glucose metabolism but not cell growth. Since PCOS usually has a menarchal age of onset, this makes it a particularly appropriate disorder in which to examine the ontogeny of defects in carbohydrate metabolism and for ascertaining large three-generation kindreds for positional cloning studies to identify NIDDM genes. Although the presence of lipid abnormalities, dysfibrinolysis, and insulin resistance would be predicted to place PCOS women at high risk for cardiovascular disease, appropriate prospective studies are necessary to directly assess this.

Steroid receptor interactions with heat shock protein and immunophilin chaperones.

Abstract: We have provided a historical perspective on a body of steroid receptor research dealing with the structure and physiological significance of the untransformed 9S receptor that has often confused both novice and expert investigators. The frequent controversies and equivocations of earlier studies were due to the fact that the native, hormone-free state of these receptors is a large multiprotein complex that resisted description for many years because of its unstable and dynamic nature. The untransformed 9S state of the steroid and dioxin receptors has provided a unique system for studying the function of the ubiquitous, abundant, and conserved heat shock protein, hsp90. The hormonal control of receptor association with hsp90 provided a method of manipulating the receptor heterocomplex in a manner that was physiologically meaningful. For several steroid receptors, binding to hsp90 was required for the receptor to be in a native hormone-binding state, and for all of the receptors, hormone binding promoted dissociation of the receptor from hsp90 and conversion of the receptor to the DNA-binding state. Although the complexes between tyrosine kinases and hsp90 were discovered earlier, the hormonal regulation or steroid receptor association with hsp90 permitted much more rapid and facile study of hsp90 function. The observations that hsp90 binds to the receptors through their HBDs and that these domains can be fused to structurally different proteins bringing their function under hormonal control provided a powerful linkage between the hormonal regulation of receptor binding to hsp90 and the initial step in steroid hormone action. Because the 9S receptor hsp90 heterocomplexes could be physically stabilized by molybdate, their protein composition could be readily studied, and it became clear that these complexes are multiprotein structures containing a number of unique proteins, such as FKBP51, FKBP52, CyP-40, and p23, that were discovered because of their presence in these structures. Further analysis showed that hsp90 itself exists in a variety of native multiprotein heterocomplexes independent of steroid receptors and other 'substrate' proteins. Cell-free systems can now be used to study the formation of receptor heterocomplexes. As we outlined in the scheme of Fig. 1, the multicomponent receptor-hsp90 heterocomplex assembly system is being reconstituted, and the importance of individual proteins, such as hsp70, p60, and p23, in the assembly process is becoming recognized. It should be noted that our understanding of the mechanism and purpose of steroid receptor heterocomplex assembly is still at an early stage. We can now speculate on the roles of receptor-associated proteins in receptor action, both as individuals and as a group, but their actual functions are still vague or unknown. We can make realistic models about the chaperoning and trafficking of steroid receptors, but we don't yet know how these processes occur, we don't know where chaperoning occurs in the cell (e.g. Is it limited to the cytoplasm? Is it a diffuse process or does chaperoning occur in association with structural elements?), and, with the exception of the requirement for hormone binding, we don't know the extent to which the hsp90-based chaperone system impacts on steroid hormone action. It is not yet clear how far the discovery of this hsp90 heterocomplex assembly system will be extended to the development of a general understanding of protein processing in the cell. Because this assembly system is apparently present in all eukaryotic cells, it probably performs an essential function for many proteins. The bacterial homolog of hsp90 is not an essential protein, but hsp90 is essential in eukaryotes, and recent studies indicate that the development of the cell nucleus from prokaryotic progenitors was accompanied by the duplication of genes for hsp90 and hsp70 (698). (ABSTRACT TRUNCATED)

The Regulation of Thyroid Function in Pregnancy: Pathways of Endocrine Adaptation from Physiology to Pathology

Abstract: I. Introduction II. The Regulation of Thyroid Function in Normal Pregnancy A. The thyroid hormone transport proteins B. The thyroid hormones 1. Total thyroid hormones 2. Free thyroid hormones 3. Peripheral metabolism of thyroid hormones C. The serum levels of thyroglobulin (TG) D. The metabolism of iodine E. The hypothalamic-pituitary control of thyroid function and the role of hCG 1. Hypothalamic-pituitary-thyroid axis (HPTA) 2. Regulation of serum TSH 3. Thyrotropic action of hCG F. A global view of thyroidal economy in pregnancy III. Pathological Alterations of Thyroidal Regulation Associated with Pregnancy A. IDD 1. Consequences of iodine deficiency during pregnancy 2. Assessment of increased thyroidal stimulation 3. Gestational goitrogenesis and its prevention by iodine supplementation 4. Consequences of iodine deficiency for the offspring B. Hypothyroidism and pregnancy 1. Fertility and pregnancy outcome in hypothyroid women 2. Thyroid hormone replacement in the hypothyroid pregnant woman 3. Subclin...

Insulin-Like Growth Factor-Binding Proteins in Serum and Other Biological Fluids: Regulation and Functions

Abstract: I. Introduction II. Characteristics of the IGFBPs III. Target Cell Actions of the IGFBPs A. To modulate IGF actions B. To facilitate storage of IGFs in extracellular matrices C. To exert IGF-independent effects IV. IGF-IGFBP Complexes in Biological Fluids A. Serum B. Milk C. Urine D. Cerebrospinal fluid (CSF) E. Follicular fluid F. Amniotic fluid G. Lymph H. Seminal fluid I. Other biological fluids V. Assays for Circulating Levels of IGFBP A. Western ligand blotting B. Western immunoblotting C. RIA D. Immunoradiometric assay (IRMA) VI. Relative Distribution of IGFBPs in Serum VII. Regulation of Serum IGFBPs A. Physiological conditions B. Development and aging C. Hormonal effects: mechanisms D. Pathological conditions VIII. IGFBP Proteases in Circulation A. Proteases under normal conditions B. Pregnancy-associated proteases C. Proteases under catabolic and disease states IX. Endocrine Functions of IGFBPs in Serum A. To prevent insulin-like effects B. To increase the half-lives of IGFs C. To control the tra...

Biological roles of fibroblast growth factor-2.

Abstract: I. Introduction II. Structure of FGF-2 III. Mechanisms of Action of FGF-2: Extra- and Intracellular Signaling A. Exogenous 18-kDa FGF-2 B. Endogenous 18-kDa FGF-2 and HMW FGF-2 IV. Release of FGF-2 V. Roles of FGF-2 in Development and Differentiation in Various Organ Systems A. Mesoderm induction B. Angiogenesis C. Vessel wall D. Lung E. Hematopoiesis F. Nervous system G. Reproductive system H. Skin I. Eye J. Muscle and skeleton K. Digestive system VI. Conclusions

Physiological action of progesterone in target tissues.

Abstract: I. Introduction II. Synthesis and Secretion of Progesterone III. The Progesterone Receptor A. PR expression and regulation IV. Progesterone Regulation of Gene Expression in the Uterus, Ovary, and Chick Oviduct A. Progesterone effects on proliferation and decidualization in the uterus during the menstrual cycle B. Progesterone regulation of insulin-like growth factor (IGF) pathways in the endometrium C. Control of ovulation D. Implantation, uterine proliferation, and early pregnancy E. Myometrial contractility F. Chick oviduct V. Progesterone Action in the Breast A. Effect of progesterone on proliferation of the normal breast B. Progesterone regulation of genes associated with cell cycle progression C. Progesterone regulation of growth factors and growth factor receptors in the breast D. Markers of progestin action in the breast E. Progesterone effects on lactation VI. Progesterone Effects in the Brain VII. Progesterone Effects on Bone VIII. Antiestrogen Action of Progesterone A. Inhibition of ER expressio...

The follicle-stimulating hormone receptor: biochemistry, molecular biology, physiology, and pathophysiology.

Abstract: I. Introduction II. Biochemical Properties of the FSH Receptor: A Historical Prelude III. Molecular Structure of the FSH Receptor A. Cloning of the FSH receptor B. Predicted primary structure of the FSH receptor C. Molecular mass of the FSH receptor IV. The FSH Receptor Gene A. Chromosomal localization B. Structure and organization of the FSH receptor gene C. The promoter of the FSH receptor gene V. Expression of the FSH Receptor and Its Regulation A. FSH receptor gene expression B. Expression of the FSH receptor in the testis C. Expression of the FSH receptor in the ovary VI. Expression of the FSH Receptor in Cell Lines A. Cell lines expressing the recombinant FSH receptor B. Measurement of FSH by means of “recombinant” in vitro bioassays C. FSH receptor function in cell lines VII. Structure-Function Relationships and Models of FSH-FSH Receptor Interaction A. General features B. Structure-function relationships C. Models of FSH-FSH receptor interaction VIII. Signal Transduction and Postreceptor Events A....

Maternal-fetal calcium and bone metabolism during pregnancy, puerperium, and lactation.

Abstract: I. Introduction II. Maternal Physiology and Pathophysiology During Pregnancy A. Maternal adaptive goals during pregnancy B. Mineral ions and calcitropic hormones C. Intestinal absorption of calcium D. Renal handling of calcium E. Skeletal calcium metabolism F. Primary hyperparathyroidism G. Hypoparathyroidism and pseudohypopara- thyroidism H. Summary III. Fetal-Placental Physiology and Pathophysiology A. Fetal adaptive goals B. Mineral ions and calcitropic hormones C. Fetal-placental calcium transport D. Renal handling of calcium and the amniotic fluid E. Skeletal calcium metabolism F. Fetal response to maternal hyper- or hypoparathy-roidism G. Integrated fetal calcium homeostasis H. Summary IV. Maternal Physiology and Pathophysiology During Lactation A. Maternal adaptive goals during lactation B. Mineral ions and calcitropic hormones C. Intestinal absorption of calcium D. Renal handling of calcium E. Skeletal calcium metabolism F. Hypoparathyroidism and pseudohypoparathy- roidism G. Summary V. Neonatal P...

Steroidogenic Factor 1: A Key Determinant of Endocrine Development and Function

Abstract: I. Introduction II. The Initial Identification of SF-1 as a Key Determinant of Steroid Hormone Biosynthesis A. Overview of steroidogenesis B. SF-1 and the regulation of steroidogenesis C. Cloning and structural characterization of SF-1 1. Structural features of SF-1 2. Multiple transcripts are encoded by the gene encoding SF-1 3. The gene encoding SF-1 is evolutionarily conserved in vertebrates and invertebrates III. Characterization of Sites of SF-1 Expression and Identification of Its Target Genes A. Profiles of SF-1 expression 1. Adult steroidogenic tissues 2. Embryonic steroidogenic tissues 3. Other sites of SF-1 expression B. Target genes regulated by SF-1 1. Steroidogenic cells 2. Sertoli cells 3. Gonadotropes 4. VMH IV. The Roles Of SF-1 in Vivo: Targeted Gene Disruption to Create SF-1 Knockout Mice A. General features of the SF-1 knockout mice B. Primary steroidogenic tissues in SF-1 knockout mice C. Pituitary and hypothalamic defects in SF-1 knockout mice V. Perspectives and Future Directions A. ...

Developmental and functional biology of the primate fetal adrenal cortex.

Abstract: I. Introduction II. Development A. Embryonic adrenal development B. Fetal adrenal development C. Neonatal adrenal development D. Growth E. Functional development 1. Ontogeny of steroidogenic activity 2. Functional zonation and ontogeny of steroidogenic enzyme expression 3. Responsiveness to ACTH III. Regulation A. The fetal pituitary and ACTH B. Growth factors 1. Basic fibroblast growth factor (bFGF) 2. Epidermal growth factor (EGF) 3. Insulin-like growth factors I and II (IGF-I and IGF-II) 4. Activin/inhibins 5. TGFβ C. Nuclear receptors/transcription factors D. Placental factors 1. Human CG (hCG) 2. Placental CRH and ACTH 3. Indirect effect of placental glucocorticoid metabolism 4. Placental estrogens IV. Physiology A. Placental estrogen formation B. Timing of parturition and fetal maturation V. Summary

11β-Hydroxysteroid Dehydrogenase and the Syndrome of Apparent Mineralocorticoid Excess

Abstract: I. Introduction II. Biochemistry of Cortisol Metabolism III. Mineralocorticoid Receptor Function A. Actions of aldosterone B. Structure and function of the mineralocorticoid receptor C. Hypothesis: 11-HSD protects the mineralocorticoid receptor IV. Loss of Function of 11-HSD A. Syndrome of apparent mineralocorticoid excess (AME) B. Licorice intoxication C. Ectopic ACTH syndrome D. Essential hypertension E. Related conditions V. Functional Roles of 11-HSD A. Liver B. Kidney and other mineralocorticoid target tissues C. Brain D. Circulatory system E. Skin F. Ovary G. Placenta H. Other fetal tissues VI. The Type I (Liver) Isozyme of 11-HSD A. Terminology B. Biochemistry C. Molecular biology D. Expression E. Lack of involvement in the syndromes of AME or 11-reductase deficiency VII. The Type 2 (Kidney) Isozyme of 11-HSD A. Biochemistry B. Molecular biology C. Expression D. Mutations in HSD11B2 are detected in all patients with AME VIII. Summary\.

Peptidomimetic regulation of growth hormone secretion.

Abstract: I. Introduction II. Identification of Peptidomimetic GH Secretagogues A. Mechanism of action of GHRH, GHRP-6, and somatostatin B. In vitro assays III. Molecular Design by Medicinal Chemistry A. Benzolactams and L-692,429 B. Spiroindanes and MK-0677 C. Isonipecotic acid peptidomimetics IV. Characterization of the MK-0677 Receptor A. Pituitary gland B. Hypothalamus V. Signal Transduction Pathway VI. Cloning the GH Secretagogue Receptor A. Chromosomal localization VII. Action of the Peptidomimetic GH Secretagogues in the Central Nervous System VIII. Peptidomimetic GH Secretagogues in Vivo A. Animal models B. Clinical studies in humans IX. Regulation of Pulsatile GH Release A. GHRH and somatostatin B. The role of GHS-R X. Concluding Comments

Roles of circadian rhythmicity and sleep in human glucose regulation

Abstract: I. Introduction II. Characteristics and Causal Mechanisms of 24-h Rhythms of Glucose Regulation in Normal Young Subjects A. 24-h variations in glucose tolerance B. Causal mechanisms III. Alterations of 24-h Rhythms of Glucose Regulation in Normal Aging A. Daytime variations in glucose tolerance B. Nighttime variations in glucose tolerance C. Respective roles of sleep and time of day D. Significance and clinical implications IV. Diurnal Variations of Glucose Regulation in Obesity A. Daytime variations in glucose tolerance B. Nighttime variations in glucose tolerance C. Significance and clinical implications V. Alterations in 24-h Rhythmicity of Glucose Regulation in Non-Insulin-Dependent Diabetes Mellitus (NIDDM) A. Alterations in daytime variations in glucose tolerance B. Alterations in nighttime variations in glucose levels during fasting C. Significance and clinical implications VI. Alterations in 24-h Rhythmicity of Glucose Regulation in Insulin-Dependent Diabetes Mellitus (IDDM) A. Alterations in dayt...

Manipulation of Human Ovarian Function: Physiological Concepts and Clinical Consequences

Abstract: I. Introduction II. Dynamics of Normal Human Follicle Growth and Selection A. Gonadotropin-independent and -dependent follicle growth B. Intrafollicular endocrine changes C. Are estrogens needed for follicle development? D. In vivo regulation of follicle maturation in the monkey E. The FSH threshold and window concept for in vivo follicle growth 1. FSH threshold and follicle recruitment 2. FSH window and single dominant follicle selection 3. Dominant follicle development F. Modulation of FSH action 1. Heterogeneity of FSH 2. Direct interference with FSH action 3. Intraovarian interference with FSH action by growth factors III. Gonadotropin Induction of Ovulation A. The concept of monofollicle growth in anovulatory patients B. Conditions affecting treatment outcome 1. Patient-related factors 2. Hormone preparation-related factors 3. Other factors involved C. Commonly used step-up dose regimens 1. Conventional step-up protocol 2. Low-dose, step-up protocol D. Potential for a step-down dose regimen IV. Stero...

Molecular Mechanisms of Ligand Interaction with the Gonadotropin-Releasing Hormone Receptor

Abstract: I. Introduction II. Amino Acid Sequences of GnRH Receptors A. GnRH receptor cDNAs B. General structural features C. Covalent modifications D. Gene structure III. Structure-Activity Relations of GnRH Peptides A. Overview B. Comparative structures and activities of vertebrate GnRHs C. Roles of individual amino acids in GnRH activity at the mammalian receptor D. Conclusions from peptide structure-activity data IV. Structure and Conformation of GnRH and Its Analogs A. Early studies of GnRH conformation B. Integrated computational and experimental studies C. Exploration of the entire conformation space of GnRH analogs V. Functional Structure of the Receptor and Ligand-Receptor Complex A. Extracellular domains B. Helix domains C. Intracellular loop domains D. Computational modeling of three-dimensional receptor structure VI. Conclusions

Molecular basis of thyroid hormone-dependent brain development.

Abstract: I. Introduction II. Developmental Schedules A. Species specificity B. Developmental studies in the rat III. Thyroid Hormone Action A. Sources of T4 and T3 B. The role of maternal thyroid hormone in fetal brain development: direct or indirect? C. Intracerebral transport IV. Molecular Actions of Thyroid Hormone in the Developing Brain A. Nuclear receptors for thyroid hormone in brain B. Thyroid hormone receptor isoforms and their tissue distribution C. Interactions of ligand, receptor, and DNA D. Ontogeny of thyroid hormone receptor isoforms in brain E. Search for T3-responsive genes in the neonatal rat brain F. Regulation of gene expression by T3 through indirect molecular pathways? G. Extranuclear actions of T4? V. Theories and Speculations VI. Conclusions

Premature ovarian failure and ovarian autoimmunity.

Abstract: Premature ovarian failure (POF) is defined as a syndrome characterized by menopause before the age of 40 yr. The patients suffer from anovulation and hypoestrogenism. Approximately 1% of women will experience menopause before the age of 40 yr. POF is a heterogeneous disorder with a multicausal pathogenesis involving chromosomal, genetic, enzymatic, infectious, and iatrogenic causes. There remains, however, a group of POF patients without a known etiology, the so-called "idiopathic" form. An autoimmune etiology is hypothesized for the POF cases with a concomitant Addison's disease and/or oophoritis. It is concluded in this review that POF in association with adrenal autoimmunity and/or Addison's disease (2-10% of the idiopathic POF patients) is indeed an autoimmune disease. The following evidence warrants this view: 1) The presence of autoantibodies to steroid-producing cells in these patients; 2) The characterization of shared autoantigens between adrenal and ovarian steroid-producing cells; 3) The histological picture of the ovaries of such cases (lymphoplasmacellular infiltrate around steroid-producing cells); 4) The existence of various autoimmune animal models for this syndrome, which underlines the autoimmune nature of the disease. There is some circumstantial evidence for an autoimmune pathogenesis in idiopathic POF patients in the absence of adrenal autoimmunity or Addison's disease. Arguments in support of this are: 1) The presence of cellular immune abnormalities in this POF patient group reminiscent of endocrine autoimmune diseases such as IDDM, Graves' disease, and Addison's disease; 2) The more than normal association with IDDM and myasthenia gravis. Data on the presence of various ovarian autoantibodies and anti-receptor antibodies in these patients are, however, inconclusive and need further evaluation. A strong argument against an autoimmune pathogenesis of POF in these patients is the nearly absent histological confirmation (the presence of an oophoritis) in these cases (< 3%). However, in animal models using ZP immunization, similar follicular depletion and fibrosis (as in the POF women) can be detected. Accepting the concept that POF is a heterogenous disorder in which some of the idiopathic forms are based on an abnormal self-recognition by the immune system will lead to new approaches in the treatment of infertility of these patients. There are already a few reports on a successful ovulation-inducing treatment of selected POF patients (those with other autoimmune phenomena) with immunomodulating therapies, such as high dosages of corticosteroids (288-292).

Molecular Endocrinology of Hydroxysteroid Dehydrogenases

Abstract: I. Introduction II. 3β-Hydroxysteroid Dehydrogenase/Ketosteroid Isomerase (3β-HSD/KSI) A. Physiological and pharmacological significance B. Cloning and expression of the 3β-HSD/KSI cDNAs C. Structure, regulation, and tissue-specific expression of the 3β-HSD/KSI genes D. 3β-HSD deficiencies III. 17β-Hydroxysteroid Dehydrogenases A. Physiological and pharmacological significance B. Cloning and expression of the 17β-HSD cDNAs C. Structure, regulation, and tissue-specific expression of the 17β-HSD genes D. 17β-HSD deficiency IV. 11β-Hydroxysteroid Dehydrogenases A. Physiological and pharmacological significance B. Cloning and expression of the 11β-HSD cDNAs C. Structure, regulation, and tissue-specific expression of the 11β-HSD genes D. 11β-HSD deficiency V. 3α-Hydroxysteroid Dehydrogenases A. Physiological and pharmacological significance B. Cloning and expression of the 3α-HSD cDNAs C. Structure, regulation, and tissue-specific expression of the 3α-HSD genes D. 3α-HSD deficiencies VI. 20α-Hydroxysteroid Deh...

Catch-up growth

Abstract: I. Introduction II. Catch-up Growth: Theoretical Considerations A. Definition B. Catch-up growth vs. compensatory growth C. Canalization D. Catch-up growth vs. resumption of a normal height velocity E. Types of catch-up growth F. Assessment of duration and success of catch-up growth III. Secondary Growth Disorders and Subsequent Catch-up Growth A. The early studies B. Malnutrition C. Celiac disease D. GH deficiency E. Hypothyroidism F. Corticosteroid excess G. Intrauterine growth retardation (IUGR) IV. Mechanisms Regulating Catch-up Growth A. The neuroendocrine hypothesis B. The growth plate hypothesis V. Determinants of Normal Growth and Their Changes During Catch-up Growth A. Introduction B. The somatotrophic axis C. The epiphyseal growth plate VI. Concluding Remarks

Anatomical and functional aspects of testicular descent and cryptorchidism.

Abstract: I. Normal Development A. Anatomical aspects 1. Sexual development 2. The gubernaculum 3. Cranial suspensory ligament 4. Abdominal pressure B. Hormonal control and functional aspects of testicular descent 1. Mullerian inhibiting substance 2. Androgen 3. The genitofemoral nerve (GFN) 4. Calcitonin gene-related peptide (CGRP) II. Cryptorchidism A. Etiology B. Frequency C. Are some UDT acquired? D. Risks of infertility/malignancy E. Role of hormone therapy F. Timing of surgery

Chick Ovalbumin Upstream Promoter-Transcription Factors (COUP-TFs): Coming of Age

Abstract: I. Introduction II. The COUP-TF Gene Family A. Homology to other members of the steroid/thyroid hormone receptor superfamily B. Sequence homology within the COUP-TF gene family III. Biochemical Characteristics A. DNA-binding sites B. Molecular mechanism of COUP-TFs action 1. Competition for occupancy of the binding sites 2. Competition for RXR 3. Active repression 4. Transrepression 5. The role of COUP-TFs in transactivation IV. Expression Patterns of COUP-TFs During Development A. Expression patterns in zebrafish and Xenopus B. Expression patterns in mouse and chick V. Physiological Function of COUP-TFs A. Ectopic expression of svp in Drosophila B. Ectopic expression of COUP-TFI in Xenopus embryos C. Loss of function of COUP-TFI in mice D. Loss of function of COUP-TFII in mice VI. Regulation of the Expression of COUP-TF Genes A. Regulation of COUP-TF by retinoids B. Regulation of COUP-TF by sonic hedgehog (Shh) VII. Perspectives

The Somatogenic Hormones and Insulin-Like Growth Factor-1: Stimulators of Lymphopoiesis and Immune Function

Abstract: I. Introduction II. Local GH Axis in Lymphoid Tissue A. Background: extrapituitary production? B. GH expression C. GH regulation D. GHRs E. GHR signaling III. GH Administration A. Effects on the thymus B. Pattern of GH exposure C. GH and immune function in humans IV. PRL A. PRL expression in lymphoid tissues B. PRL receptors C. Administration of PRL, anti-PRL antibodies, or bromocriptine V. Insulin-like Growth Factors A. Background B. IGF peptides C. Regulation of lymphocyte IGF-I D. IGF receptors on lymphocytes E. IGFBPs VI. Actions of IGF-I A. Bone marrow B. Effects on lymphoid organ size C. Effect of in vivo treatment on lymphocyte number and in vitro function D. Functional effects of IGF-I in vivo: antibody responses E. Immune reconstitution F. Mechanism of action: apoptosis VII. IGF-I in Different Physiological States A. IGF-I in pregnancy B. IGF-I in diabetes C. IGF-I in gastrointestinal disorders D. IGF-I action in polycythemia vera VIII. GH/IGF-I as Antistress Hormones IX. Therapeutic Potential X....

Gonadal Peptides as Mediators of Development and Functional Control of the Testis: An Integrated System with Hormones and Local Environment

Abstract: I. Introduction II. Neurohormones/Neuropeptides A. GH-releasing hormone (GHRH) B. Pituitary adenylate cyclase-activating peptide (PACAP) C. GnRH D. CRH E. Oxytocin (OT) F. Arginine vasopressin (AVP) G. TRH H. Somatostatin (SRIF) I. Opioids J. Substance-P (SP) K. Neuropeptide Y (NPY) III. Peptides Originally Identified in the Male Gonad A. Inhibin (INH) and activin (ACT) B. PModS IV. Growth Factors A. Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBs) B. Transforming growth factor-β (TGFβ) C. TGFα/EGF D. Fibroblast growth factor (FGF) E. Platelet-derived growth factor (PDGF) F. Nerve growth factor (NGF) G. Steel factor (SLF) H. Gastrin-releasing peptide (GRP) V. Immune Derived Cytokines A. Interleukins (ILs) B. Tumor necrosis factor-α (TNFα) VI. Vasoactive Peptides A. Endothelin (ET) B. Angiotensin-II (AT-II) C. Atrial natriuretic peptide (ANP) VII. Conclusions and Perspectives

Studies of gonadotropin-releasing hormone (GnRH) action using GnRH receptor-expressing pituitary cell lines.

Abstract: I. Introduction II. GnRHR Structure Analysis III. Studies of GnRH Action in αT3-1 Cells A. Derivation of αT3-1 cells B. Characterization of αT3-1 cells C. GnRH binding D. GnRHR regulation 1. Homologous regulation by GnRH 2. Regulation by gonadal steroid hormones 3. Regulation by gonadal peptides 4. Regulation by second messenger activators E. Intracellular second messengers 1. G protein coupling 2. Inositol phosphates 3. Intracellular calcium 4. Protein kinase C 5. cAMP 6. Mitogen-activated protein kinases F. α-Subunit gene expression 1. Cell-specific expression 2. GnRH-stimulated expression G. Desensitization H. Summary of GnRH action in αT3-1 cells IV. Studies of GnRH Action in GH3 Cells Transfected with the GnRH Receptor (GGH3 Cells) A. Derivation of GH3 cells B. Characterization of GH3 cells C. Derivation of GH3 cells transfected with the GnRHR (GGH3 cells) D. GnRH binding E. GnRHR regulation F. Intracellular second messengers 1. G protein coupling 2. Inositol phosphates 3. cAMP G. Regulation of secre...

Pituitary Cytokine and Growth Factor Expression and Action

Abstract: The complex range of pituitary regulatory mechanisms reviewed here underlies the critical function of the pituitary in sustaining all higher life forms. Thus, the ultimate net secretion of pituitary hormones is determined by signal integration from all three tiers of pituitary control. It is clear from our current knowledge that the trophic hormone cells of the anterior pituitary are uniquely specialized to respond to these signals. Unravelling their diversity and complexity will shed light upon the normal function of the master gland. Understanding these control mechanisms will lead to novel diagnosis and therapy of disordered pituitary function (357).

Excitatory amino acids: evidence for a role in the control of reproduction and anterior pituitary hormone secretion.

Abstract: I. Introduction II. The EAA System: Overview, Description, and Localization in Neuroendocrine Tissues A. Endogenous EAAs and their localization in the hypothalamus B. Types of EAA receptors and their localization in the CNS and hypothalamus C. EAA transporters III. EAAs and Reproduction A. Effect of EAA agonists on LH secretion B. Effect of blockade of EAA neurotransmission on the steroid-induced and preovulatory LH surge and pulsatile LH secretion C. Site of action of EAAs in the control of LH secretion D. Mechanism of action of EAAs in the control of LH secretion E. The opioid-glutamate-nitric oxide-guanylate cyclase pathway in the control of GnRH secretion: a proposed model IV. Role of EAAs in Puberty and Reproductive Behavior A. Role of EAAs in puberty B. EAAs and reproductive behavior V. Role of EAAs in the Secretion of Other Anterior Pituitary Hormones A. ACTH B. GH C. PRL VI. Conclusions

Novel Insights into the Molecular Mechanisms of Human Thyrotropin Action: Structural, Physiological, and Therapeutic Implications for the Glycoprotein Hormone Family

Abstract: I. Introduction A. Historical background B. TSH and the glycoprotein hormone family II. Structure-Function Relationships of TSH in Relation to Studies on Gonadotropins A. Methodological considerations B. Structure-function studies of protein domains C. Structure-function studies of carbohydrate chains III. Current Understanding of TSH/Glycoprotein Hormone Action A. Structural considerations B. Hormone-receptor interaction C. Cooperation of individual hTSH domains in receptor activation IV. Physiological and Pathophysiological Implications A. Carbohydrate heterogeneity B. Naturally occurring glycoprotein hormone mutations C. “Specificity spillover” syndromes V. Evolutionary Considerations A. Glycoprotein hormone specificity B. Evolutionary changes in TSH activity VI. Strategies in the Design of Novel TSH Analogs and Therapeutic Implications A. Clinical use of rhTSH B. Design of novel glycoprotein hormone analogs VII. Nonclassic Actions of TSH and Gonadotropins A. Extrathyroidal/extragonadal glycoprotein ho...

Molecular Genetics of Human Hypertension: Role of Angiotensinogen

Abstract: I. Introduction II. Structure of the AGT Gene III. Characteristics of AGT A. AGT as the substrate for renin B. AGT as a member of the serpin superfamily: other roles for AGT? IV. Tissue and Cellular Distribution V. Regulation A. Hormonal regulation of AGT B. Regulation of AGT in disease C. Regulation of AGT gene transcription VI. Molecular Genetics of AGT in Human Essential Hypertension A. Strategies B. Linkage studies C. Association studies of AGT polymorphism and high blood pressure D. Pregnancy-induced hypertension E. M235T variants, plasma AGT concentration, and blood pressure F. Association of AGT variants with the renal blood flow response to Ang II infusion VII. Molecular Genetics of AGT and Other Diseases A. AGT variants and coronary heart disease B. AGT variants and complications of diabetes C. AGT, obesity, and blood pressure VIII. Effects of AGT Gene Variants and Gene Targeting on Ang I Production and Blood Pressure A. Human studies B. Genetic studies in rats and mice C. Genetic hypertension in...