Epidermal growth factor-related peptides and their receptors in human malignancies

The goal of this review is to place the exciting advances that have occurred in our understanding of the molecular biology of the types 1, 2, and 3 (D1, D2, and D3, respectively) iodothyronine deiodinases into a biochemical and physiological context. We review new data regarding the mechanism of selenoprotein synthesis, the molecular and cellular biological properties of the individual deiodinases, including gene structure, mRNA and protein characteristics, tissue distribution, subcellular localization and topology, enzymatic properties, structure-activity relationships, and regulation of synthesis, inactivation, and degradation. These provide the background for a discussion of their role in thyroid physiology in humans and other vertebrates, including evidence that D2 plays a significant role in human plasma T3 production. We discuss the pathological role of D3 overexpression causing “consumptive hypothyroidism” as well as our current understanding of the pathophysiology of iodothyronine deiodination during illness and amiodarone therapy. Finally, we review the new insights from analysis of mice with targeted disruption of the Dio2 gene and overexpression of D2 in the myocardium. (Endocrine Reviews 23: 38–89, 2002)

Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases.

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...

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

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Neuroendocrine perspectives on social attachment and love

Background: A number of recent advances in our understanding of thyroid physiology may shed light on why some patients feel unwell while taking levothyroxine monotherapy. The purpose of this task force was to review the goals of levothyroxine therapy, the optimal prescription of conventional levothyroxine therapy, the sources of dissatisfaction with levothyroxine therapy, the evidence on treatment alternatives, and the relevant knowledge gaps. We wished to determine whether there are sufficient new data generated by well-designed studies to provide reason to pursue such therapies and change the current standard of care. This document is intended to inform clinical decision-making on thyroid hormone replacement therapy; it is not a replacement for individualized clinical judgment. Methods: Task force members identified 24 questions relevant to the treatment of hypothyroidism. The clinical literature relating to each question was then reviewed. Clinical reviews were supplemented, when relevant, with related...

Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement

Publisher Summary This chapter discusses the maturation of hypothalamus and thyroid function It also discusses the maturation of the neurovascular communication system between the hypothalamus and pituitary in a newborn rat It is a progressive process continuing throughout the period of hypothalamic maturation By 17 days of gestation, the pituitary gland is surrounded by a capillary network and separated from the brain by a thin layer of mesenchyme and capillaries—this is referred to as the supra-tuberal plexus, or the secondary plexus of the portal system The chapter illustrates Triiodothyronine (T3) production rates in rats at different times after birth In the illustration, T3 production rates, per 100 body weight are plotted as mean and SEM The general pattern of ontogenesis of the hypothalamic-pituitarythyroid system in the human, sheep, and rat species is similar The timing of the several stages relative to parturition differs in the rat Human and sheep fetuses are delivered toward the end of the stage of development of neuroendocrine control and early in the period of maturation of tissue metabolic systems In contrast, the rat is delivered soon after completion of embryogenesis of the thyroid and pituitary glands early in stage II maturation of the hypothalamus

Ontogenesis of hypothalamic--pituitary--thyroid function and metabolism in man, sheep, and rat.

The initial observations of Stanley Cohen in the 1960s established that EGF induced in vivo effects such as precocious eyelid opening and tooth eruption. Subsequently the actions of EGF have been extensively explored in cell culture systems. The receptor for EGF was characterized as a prototype model for other growth factors and the now extensive in vitro data indicate multiple functions for EGF. Moreover, EGF and EGF receptors have been characterized in many tissues, and EGF has been identified in most body fluids of several mammalian species. Interestingly, neither EGF antibody administration to newborn animals nor passive immunization of pregnant rodents against EGF has caused major deleterious effects (except the delay in epidermal maturation events), as might be expected from the in vitro studies. This is in contrast to the effects of nerve growth factor antiserum in developing rodents. Also, to date, no pathological EGF deficiency disorder has been characterized. However, the EGF family of growth factors appears to be important in mammalian development and function, although the precise roles and significance are not yet clear. Members of the family may have a role in embryogenesis and fetal growth since receptors have been identified in fetal tissues. Available evidence suggests that TGF alpha subserves the growth factor family roles in fetal development. In the developing postnatal animal pro-EGF mRNA, immunoreactive EGF, immunoreactive TGF alpha, and EGF receptors are present in many tissues. EGF also is produced and secreted by the maternal mammary gland, and mammary derived EGF appears to be important in gut development in the neonatal rodent. There is now extensive data to indicate important hormone-EGF interactions. In the postnatal period, thyroid and steroid hormones including retinoic acid have been shown to modulate EGF and/or EGF receptors in several tissues. GH increases EGF binding in liver and increases urine EGF concentrations. Moreover, EGF stimulates secretion of several hypothalamic and pituitary hormones, increases placental production of hCG and human chorionic somatomammotropin, increases adrenal cortisol production, and inhibits testicular, ovarian, and thyroid hormone secretions. As summarized in this review EGF has been implicated in a number of developmental events including palate and skin differentiation, growth of hair follicles, eye opening and tooth eruption, lung maturation, gut and liver growth, and differentiation of neurons. These EGF actions probably are mediated via autocrine, paracrine, and endocrine routes. A role for salivary and urine EGF in the maintenance of adult stomal, gut, and urinary epithelial surface integrity seems likely, although not yet proven.(ABSTRACT TRUNCATED AT 400 WORDS)

Metabolism and effects of epidermal growth factor and related growth factors in mammals.

Screening for congenital hypothyroidism: Results of screening one million North American infants

The present report describes the development of a sensitive and specific radioimmunoassay system (RIA) for measurement of arginine vasopressin (AVP) in serum or plasma. The RIA has a sensitivity of 0.3–0.5 μU/ml and employs an extraction procedure utilizing the diatomaceous earth Bentonite. This procedure also permits AVP measurements in maternal and fetal blood in the presence of elevated levels of vasopressinase. Serum AVP concentrations were measured in normal adult subjects in various states of hydration and in selected patients with abnormalities of AVP metabolism. The RIA results are in good agreement with previously reported bioassay results.

Radioimmunoassay measurement of arginine vasopressin in serum: development and application.

The diurnal variation in thyroidal iodine release previously observed in euthyroid subjects appears to correlate with variations in serum immunoassayable thyrotropin (TSH). The hypothesis is advanced that this diurnal rhythm seems to be primarily regulated by a negative feedback action of circulating hydrocortisone. The administration of maintenance doses of hydrocortisone to patients with primary adrenal insufficiency and pharmacological doses to euthyroid subjects was accompanied by an acute suppression in both thyroidal iodine release and serum TSH values. An escape from glucocorticoid suppression was observed to occur in 2 or 3 days with the resumption of a near-normal thyroidal iodine release rate but was accompanied by a dampening or absence of the normal diurnal rhythm. Withdrawal of pharmacological doses of glucocorticoids in euthyroid subjects and maintenance doses in primary hypoadrenal patients was accompanied by transient stimulation of both serum TSH and thyroidal iodine release values. The study of a patient before and after cryohypophysectomy indicated that the rebound response in thyroid release after steroid withdrawal may be a useful testing procedure to indirectly assess the hypothalamicpituitary reserve capacity of TSH.

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Delbert A. Fisher

Papers

Ontogenesis of hypothalamic--pituitary--thyroid function and metabolism in man, sheep, and rat.

Metabolism and effects of epidermal growth factor and related growth factors in mammals.

Screening for congenital hypothyroidism: Results of screening one million North American infants

Radioimmunoassay measurement of arginine vasopressin in serum: development and application.

The Role of Glucocorticoids in the Regulation of Thyroid Function in Man