Showing papers in "Endocrine Reviews in 1984"

Physiological Functions of Glucocorticoids in Stress and Their Relation to Pharmacological Actions

Abstract: Introduction and Background Modern glucocorticoid endocrinology is a colorful, richly varied, but formless discipline—a profusion of cellular, physiological and pharmacological effects, seemingly unrelated through any central hormonal function. A current list of glucocorticoid effects might include such disparate items as stimulation of hepatic gluconeogenesis, inhibition of glucose uptake by peripheral tissues, suppression of inflammation, enhanced excretion of a water load, induction in various cells of tryptophan oxygenase and glutamine synthetase, suppression of numerous immune reactions, inhibition of secretion of several hormones and neuropeptides, and inhibition of activity of plasminogen activator and other neutral proteinases. Judging from recent writings on glucocorticoid physiology, an item that might be low on the list or missing altogether is “increased resistance to stress”.

Corticosteroid inhibition of ACTH secretion.

Abstract: THE LEVEL of activity within the adrenocortical system is determined by endogenous (circadian) and exogenous (stress) excitatory inputs, by inhibitory neural modulation and also by corticosteroid negative feedback control. Although corticosteroid feedback on (CRF and) ACTH secretion is easily demonstrated by treatment of mammals with exogenous glucocorticoids and subsequent measurement of either basal or stimulated activity in the system, the physiological role of this negative feedback is not so easily discerned. It is likely that most disagreement about feedback regulation of ACTH secretion has arisen because of three characteristics of the system. First, it now appears that there are at least three distinct time domains in which negative feedback by glucocorticoids on ACTH secretion are exerted. These can be distinguished at the level of the corticotrope in vitro by the different cellular effects of glucocorticoid action. Thus, interpretation of results of in vivo experiments is critically dependent on...

Hormonal regulation of the differentiation of cultured ovarian granulosa cells

Abstract: 1. Cell Culture Approach to the Study of Granulosa Cells In 1672, Regnier de Graaf first described the differentiation of ovarian follicles into the corpus luteum. He stated that “age and coitus cause very great changes in eggs (follicles). In young animals, they are very small and in more developed ones they are larger. After coitus, they (the follicles) so alter as to resemble the globules (the corpora lutea) …, being one or more according as the animal will produce one or more fetuses.” (1) Follicles as the functional unit: Ovarian follicles have since been shown to be the basic functional unit of the ovary and consist of an outer layer of theca interna cells which encircle inner layers of granulosa cells. Granulosa cells, in turn, surround the innermost oocyte-cumulus cell complex. The maturation of ovarian follicles and their transformation into corpora lutea is regulated by a specific set of hormones and has been a major research area for ovarian physiologists for several hundred years.

Regulation of the Immune System by Sex Steroids

Abstract: Introduction IN THE PAST 10 years there has been a significant increase in studies relating to the function of the immune system. The recent popularity of research in this area is due in part to the awareness by the medical and scientific community of the importance of immune function in the maintenance of a disease-free homeostasis, to technological advances in the field of immunological research, and to the increased availability of funds for investigation in this area. From the rapidly expanding literature in this field it has become increasingly apparent that the immune system interacts with most, if not all, of the body systems. One of the most intriguing of these interrelationships is that which occurs between the immune and reproductive systems and involves interactions of pituitary hormones, gonadal steroid hormones and thymic hormones. Because of the complexity of this area the present review will concentrate on only one aspect of the interaction between the two systems, namely the effects of gon...

Autoimmune thyroid disease: developments in our understanding.

Abstract: INTRODUCTION THIS REVIEW of autoimmune thyroid disease will highlight the recent advances made in understanding the control of the autoimmune process particularly at pathogenetic and therapeutic levels Many novel techniques have recently been applied to the investigation of thyroid autoimmunity although the results obtained have not always clarified the overall picture These new methodologies are discussed and attention is also focused upon experimental thyroiditis produced in a variety of animals We believe that these models have been neglected somewhat by clinically oriented investigators Yet their use originally led to the foundation of autoimmune concepts, and experimental thyroiditis continues to provide major insights into the possible etiology and pathogenesis of the human counterpart Before discussing thyroid disease in detail however, it is worth considering the current themes in autoimmunity in general

Ovarian and Steroidal Influences on Neuroendocrine Aging Processes in Female Rodents

Abstract: Some Mammalian aging processes involve effects of steroids on the brain and pituitary. An ovary-dependent, neuroendocrine aging syndrome of laboratory rats and mice is described in this article. This syndrome can be attenuated during aging by chronic ovariectomy and can be prematurely induced in young rodents by sustained exposure to estradiol (E2). The limited follicular stock in the ovary is proposed to be a major pacemaker of aging in this neuroendocrine syndrome; ovarian aging may interact with neuroendocrine aging. Ovary-independent neuroendocrine changes occur as well. We also discuss developmental influences on adult aging in rodents and other examples in which adult lower mammals are sensitive to long lasting effects of steroids on the brain and pituitary. Possible molecular mechanisms are considered. In view of the long lasting effects of E2 and other steroids on lower mammals, the potential for long term effects of ovarian steroids on the human brain and pituitary warrants continued evaluation.

The Deiodination of the Iodothyronines and of Their Derivatives in Man

Abstract: THYROIDAL secretion is the only source of thyroxine (T4) in the human systemic circulation, and in euthyroid man, T4 is the main secretory product of the gland. The metabolic fate of the hormone once thyroidal secretion has occurred is complex and involves deiodination, deamination and decarboxylation of the amino acid side chain, and esterification of the phenolic hydroxyl group with glucuronic or sulfuric acid. These pathways are not to be considered as mutually exclusive, but are interrelated in an exceedingly complex manner. Deiodination of T4 is the most important degradative pathway and accounts for up to 85% of the disposal of the hormone (1–3). At least two major mechanisms exist within the peripheral tissues by which the iodine atoms may be removed from the molecule. Of these, monodeiodination is quantitatively the most important pathway and has been subjected to the most intensive investigation.

Growth-stimulatory actions of insulin in vitro and in vivo.

Abstract: Insulin stimulates the growth and proliferation of a variety of somatic cells in culture, and evidence suggests that insulin is also an important regulator of growth in vivo. In cell culture, insulin interacts synergistically with other hormones and growth factors such as platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), tumor-promoting phorbol esters, and thrombin, to stimulate progression through the cell cycle of cells that have been arrested in G1 by deprivation for serum. In addition, insulin is required by most cells for optimal long term growth in hormone-supplemented serum-free media. In some cells, such as human skin fibroblasts, the growth-promoting effects of insulin appear to be mediated primarily by its low affinity interaction with receptors for insulin-like growth factor I (IGF-I). In other cells, such as hepatocytes, hepatoma cells, adrenocortical tumor cells, mammary carcinoma cells, and F9 embryonal carcinoma cells, insulin appears to stimulate growth by binding to high affinity insulin receptors. The insulin and IGF-I receptor proteins, like the receptor proteins for other growth-promoting hormones such as EGF and PDGF, are closely associated with tyrosine-specific protein kinase activities. The mechanism by which the binding of insulin to its receptor and activation of the receptor-associated tyrosine protein kinase activity control intracellular protein phosphorylation and dephosphorylation reactions, such as the phosphorylation of ribosomal protein S6, is a subject of considerable current interest. The phosphorylation of ribosomal protein S6 may be related mechanistically to the activation by insulin of protein synthesis, and hence the passage of cells through the G1 phase of the cell cycle. Malignant transformation does not generally result in a total loss of the growth requirement of cells for insulin or insulin-like growth factors, although transformation is accompanied in some cases by a qualitative reduction in the insulin/IGF requirement. Abnormalities in insulin production or sensitivity in vivo are accompanied by abnormalities in growth; thus, insulin appears to be an important regulator of growth in vivo. Some of the growth-promoting effects of insulin in vivo may be attributable to direct action of insulin, while other effects may be caused by the regulatory effect of insulin on somatomedin production, and possibly on somatomedin action.

Endocrine Response in the Fallopian Tube

Abstract: I. INTRODUCTION: STRATIFICATION OF TUBAL ENDOCRINE RESPONSE THE FALLOPIAN TUBE has, until very recently, been essential for human reproduction. Sperm transport and capacitation, ovum transport, fertilization, and early embryogenesis are fundamental reproductive events that normally take place in its lumen. Although in recent times in vitro fertilization (IVF) procedures have sought to mimic the tube's luminal environment, the still limited success of IVF carries the certain implication that more detailed knowledge of fallopian tube function may not only improve treatment of its anatomical and physiological disturbances but also should provide a better empirical basis for its in vitro counterpart. Fallopian tube physiology is exquisitely dependent on hormones. The responsive tissues include the muscle layer (or myosalpinx), the vasculature, the epithelium (or endosalpinx) and, most important, the fluids contained in the lumen. Intricate tiers of endocrine influences and responses in the human fallopian tub...

Endocrine ophthalmopathy: current ideas concerning etiology, pathogenesis, and treatment

Abstract: ALTHOUGH the association of exophthalmos with goiter was recognized as early as the twelfth century (1), the modern focus on the constellation of hyperthyroidism, diffuse goiter, and endocrine ophthalmopathy is best attributed to the work of Caleb Parry (1825) (2), Robert Graves (1835) (3), and Carl von Basedow (1840) (4). Since their early descriptions a plethora of reports have been published detailing the clinical and histologic features of endocrine ophthalmopathy and coining a variety of colorful synonyms and eponyms (5, 6). There remained, however, a number of important unanswered questions. These deal with the nature of the inciting factor, the pathogenesis of the disease, the unique and often asymmetric involvement of extraocular muscles, the relationship between the eye disease and the thyroid abnormality, and the most rational and efficacious methods of treatment. We will review the clinical, anatomic, histologic, and immunologic features of endocrine ophthalmopathy particularly as they apply to...

Aspects of the pathogenesis of type 2 diabetes.

Abstract: SINCE pancreatectom in dogs resulted in hyperglycemia (1) which was reversed by treatment with the product of the pancreatis islets (2, 3), diabetes was considered to be due to insulin deficiency. This view was questioned almost 50 years ago when Himsworth suggested that diabetic patients could be subdivided into two groups: insulin-sensitive and insulin-insensitive (4). Later, Himsworth pointed out that insulin-sensitive patients tended to be ketosis-prone, while insulin-insensitive patients were usually middle-age diabetics without tendency to ketosis (5). Himsworth's concept gained support by the findings that plasma insulin activity, determined by biological assays, was absent in diabetics with weight loss and ketosis but was essentially normal in overweight diabetics without ketosis (6). Subsequently, a strong proof for the concept was provided when Yalow and Berson (7), using their specific sensitive radioimmunoassay for insulin, demonstrated that, in response to provocative testing, plasma insulin ...

Thyroid Hormones, Gonadal and Adrenocortical Steroids and the Function of the Islets of Langerhans

Abstract: Thyroid hormones, gonadal and adrenocortical steroids, are glucoregulatory hormones. Thyroid hormones increase the provision of glucose to meet the enhanced energy demands which they impose. Glucose tolerance is decreased, associated with increased hepatic glucose production, although the glucose-raising effects of thyroid hormones are partially offset by an increased rate of glucose utilization especially in the postabsorptive state. The insulin secretory capacity of the pancreatic B cells is reduced by an excess of thyroid hormones, and the onset of diabetes may be hastened as pancreatic insulin reserves are depleted. Natural estrogens can improve glucose tolerance through a beta-cytotropic effect and enhanced insulin sensitivity. Progesterone may produce similar effects in the absence of estrogens, but progestins appear to antagonize the effects of estrogens. Testosterone exerts only marginal effects on glucose tolerance. Glucocorticoids decrease glucose tolerance by increased hepatic glucose production and impaired peripheral glucose utilization. Glucocorticoids reduce insulin sensitivity and responsiveness in peripheral tissues. However, the diabetogenic influence of glucocorticoid excess is partly compensated by a beta-cytotropic effect and a condition of diabetes develops when the functional reserve of the endocrine pancreas becomes limiting.

Normal and Abnormal Function of the Hypothalamic Pituitary-Adrenocortical System in Man*

Abstract: The first half of this manuscript is devoted to a review of the methods used and the results obtained in the published measurements of the normal responses to tests of the three main types of hypothalamic-pituitary-adrenocortical (HPA) activity in man. These are, I, basal, unstressed activity leading to appropriate levels of total daily production of cortisol in the characteristic circadian pattern; II, responses to feedback stimulation of HPA activity by metyrapone administration; and III, responses to tests of the effects of stress on the HPA system including the effects of hypoglycemia, induced fever, vasopressin administration, and ACTH injections and infusions. The advantages and shortcomings of each type of procedure are discussed. The second half of this paper describes the authors' attempts to establish the limits of normality of standard and modified methods of evaluating the HPA system. The defined limits of normality have been used to assess the HPA function in 158 patients with known or suspected disorders of the HPA system. In normal controls, halfhourly plasma cortisol determinations established the normality of circadian and postprandial fluctuations and of mean plasma cortisol concentration, 6.2 +/- 0.3 (SEM) micrograms/dl, which were closely approximated by determinations every 6 h. Metyrapone, given in a dose of 500 mg every 2 h for 24 h increased urinary 17-OHCS excretion to 10.5-32.6 mg/day or to 1.7-7.8 times basal excretion rate. Increasing rates of insulin infusion disclosed significant relationships between resulting plasma glucose and cortisol concentrations. The slopes of the delta cortisol/delta glucose responses were similar after insulin infusions (0.46 +/- 0.05) and after insulin injections, 0.15 U/kg (0.43 +/- 0.09), and were always greater than 0.20 micrograms/mg. This index provides a useful objective measure of the normality of responses to hypoglycemic stress, 0.20-0.87 micrograms/mg. Adrenocortical responses to iv infusions of ACTH (cosyntropin 0.25 mg) may be equivocal at 2 h but are clear cut at 4, 6 and 8 h. Of 158 patients in whom hypopituitarism was known or suspected because of the presence of a pituitary tumor, acromegaly, hyperprolactinemia, or clinical features, HPA function was found to be entirely normal in 88 patients and partially or severely abnormal in the remaining 70 patients.(ABSTRACT TRUNCATED AT 400 WORDS)

A Heuristic Proposal for Understanding Steroidogenic Processes

Abstract: Introduction The generally accepted pathways of steroidogenesis are customarily presented by a scheme such as that shown in Fig. 1. This two-dimensional picture can be conveniently reproduced on a printed page and is easily memorized. It provides, however, too simplistic a view which can lead to serious misconceptions. By depicting the biochemical transformations it concentrates on the apparent common features of the various pathways but ignores many important differences. The scheme indicates that one sterol, cholesterol, serves as a precursor for all the hormones. The possibility that other derivatives of cholesterol may also be progenitors of important steroidal products is not taken into account. Cholesterol esters, particularly cholesterol sulfate, are examples of such precursors. For more than 15 years (1) it has been known that the abundant adrenal secretory product, dehydroisoandrosterone sulfate, can be biosynthesized from cholesterol sulfate through pathways that involve sulfated intermediates w...

The Renin-Angiotensin System in Nonmammalian Vertebrates*

Abstract: Introduction The purpose of this review is to appraise the results of the comparative approach to an endocrine system, the renin-angiotensin system (RAS). Recognizing that animal life is a product of history, comparative endocrinology tries to account for the structure and function of endocrine systems as products of evolution. Its characteristic method is the study of homologies, those resemblances among species resulting from derivation from a common ancestry on which natural selection has operated to produce adaptations. Why the comparative approach to the RAS? In addition to their intrinsic interest, comparative studies are of contextual importance to the understanding of mammalian endocrinology. Insights gained from the study of primitive organisms often are valid even at the level of complexity represented by the most recent vertebrates because animals considered primitive on phylogenetic scales nevertheless possess many of the same components as organisms at higher levels. Furthermore, the comparat...

The cold thyroid nodule: an analysis of diagnostic and therapeutic options.

Abstract: We applied decision analysis to the controversy over the management of the solitary nonfunctioning thyroid nodule. Three standard management plans were considered: immediate subtotal thyroidectomy; a six month trial of thyroid suppression with L-thyroxine, with non-suppressible lesions being removed surgically; and aspiration cytology followed by surgery or thyroid suppression based on the cytologic examination. The literature formed the basis for quantitative assumptions of the analysis, including the consequences of thyroidectomy, the probability of malignancy, the types and prognoses of cancers found at operation, the likelihood of successful suppression adn relapse, and the possible results of aspiration cytology. We used Bayes' rule to revise the probability of cancer on the basis of cytological results. The relative worths of the 59 possible diagnostic and therapeutic outcomes were expressed as quality-adjusted life expectancies. The expected utility of each management plan was determined by "folding back" the decision tree. Although we found that each possible approach yielded a quality-adjusted life expectancy very close to that of the healthy population, aspiration biopsy with cytologic examination appeared slightly superior. Extensive sensitivity analyses demonstrated that either aspiration biopsy or immediate thyroid suppression was the treatment of choice over a wide range of assumptions, although in no case did the benefit exceed 1 year of life. We conclude that all therapies for cold thyroid nodule are essentially equal, viewed in terms of mortality and morbidity. The decision to operate, suppress or aspirate is thus a " tossup ", dependent in the individual case upon such subjective factors as psychological disutility , relative cost, and attitudes toward operative risk and long-term medical therapy. The controversy concerning the "best" management of the cold thyroid nodule is an illusion: quantitative analysis shows the futility of pursuing the debate any further.

Update on in vitro fertilization.

Abstract: I. Introduction THE TECHNIQUE for in vitro fertilization was originally devised by Edwards and Steptoe (1) for the relief of otherwise uncorrectable tubal infertility. Oocytes are retrieved surgically from the Graafian follicles and fertilized in the laboratory with the husband's sperm. The conceptus is cultured for 40 h, at which time it is transferred into the uterus at the four-cell stage. A program for in vitro fertilization, therefore, involves the marriage of three major disciplines: reproductive surgery, embryology, and endocrinology; with surgery for the retrieval and transfer of the oocyte and conceptus; embryology for the oocyte culture and fertilization; and endocrinology for stimulation of multiple follicle development. The importance of surgical skills is self-evident, as laparoscopic oocyte retrieval may be difficult in patients who have had multiple operative procedures. Because the procedures are done under anesthesia, hospital facilities, at least on an outpatient basis, are a requirement.

Hypothyroidism: diversity of presentation.

Abstract: Hypothyroidism has a number of signs and symptoms known to most all clinicians. However, the disorder has many other presentations that are less frequently recognized. These other manifestations, though not seen often, are also not uncommon. Hypothyroidism is an easily treated, frequent disease, and can be misdiagnosed for years before becoming apparent. Although its symptoms are usually readily reversible with treatment, lack of recognition of its rarer signs and symptoms can lead to unnecessary morbidity. Awareness of the diversity of presentation of this disease may lead to early, effective treatment.

The Pineal Gland: Basic Implications and Clinical Correlations

Abstract: Introduction THE PINEAL gland has received increasing interest from investigators during the past decade. As the pineal has become more intensively investigated, its involvement in the modulation of specific endocrine systems, in particular the gonadal system, has become more clearly delineated. Due to the obvious difficulty in obtaining human material with which to work, investigators by necessity have concentrated their efforts in determining pineal gland function by utilizing a number of subhuman mammals, primarily the rat and the hamster. This review will discuss the historical literature relevant to the pineal gland, the anatomy of the pineal gland including neural and vascular connections, and the histological appearance of the vertebrate pineal gland. The biologically active substances which have been identified within the pineal gland will be discussed, with particular emphasis on the synthesis of melatonin and the photoperiodic and hormonal modulation of melatonin synthesis. Evidence which is cur...

Multiple Effects of 5,5'-Diphenylhydantoin on the Thyroid Hormone System*

Abstract: The studies described above indicate the likelihood of a significant effect of DPH on cellular functions that are regulated by T3 at concentrations of DPH that occur during treatment of patients with Dilantin. Thus, it is possible that sensitive measures of cellular thyroid status in man, if available, might indicate that DPH treatment causes a mild hypothyroid state which may be partially compensated for by an activity of DPH as a partial thyroid hormone agonist. This review illustrates the complex array of interactions of DPH with multiple elements of the thyroid hormone system ranging from effects on T4 and T3 metabolism, serum protein binding, serum and cellular concentration of thyroid hormones, nuclear T3 binding and biologic actions of T3, to effects on hypothalamic and pituitary regulation of TSH. At the present time, no single biological mechanism common to these manifold interactions is apparent. Moreover, many of these interactions are not yet completely understood despite clinical and basic biological investigation for over 20 years. Continued investigation would appear fruitful especially for further understanding of hypothalamic regulation of TSH secretion, of cellular uptake of T3, and of the use of DPH as a partial thyroid hormone agonist. Finally, since DPH attenuates the effect of T3 at the level of the nuclear T3 receptor, the drug may serve as a prototype of agents that may be useful in the management of thyrotoxicosis.

Female hirsutism: pathophysiological considerations and therapeutic implications.

Abstract: INTRODUCTION FEMALE HIRSUTISM may be defined as excessive hair growth in anatomical sites where such growth is considered a secondary male characteristic. Although this disorder can be a symptom of a number of endocrine diseases such as polycystic ovarian disease (PCO) or Cushing's syndrome, most patients present with no obvious abnormalities of endocrine function. The term that has been applied to this condition is idiopathic or simple hirsutism. Idiopathic hirsutism shows no clinical differences from other types of hirsutism. However, it is generally not associated with other signs of hyperandrogenism such as virilization of the external genitalia, deepening of the voice, breast atrophy, or development of a male-type muscle bulk. Although racial differences have been noted in the occurrence of this disorder (Mediterranean women being more subjected to abnormal hair growth), no such differences have been found in androgenic steroids (1). Starting with the concept that hair follicles as well as sebaceous ...

The Scintigraphic Imaging of Endocrine Organs

Abstract: The nuclear medicine approach to the portrayal of endocrine organs is unique; the scintigraphic images provide not only anatomic and localization information, but in many instances allow a quantitative assessment of organ function. The ability to image endocrine glands is based upon the design of radionuclides and radiopharmaceuticals with characteristics to take advantage of many unique and specific biochemical and advantage of many unique and specific biochemical and metabolic functions of these tissues. The recent introduction of new radiopharmaceutical and tracers has provided the consulting endocrinologist with imaging procedures that allow localization and functional characterization not available by other single, noninvasive diagnostic modalities. This review will serve as an update of the available techniques to image and quantitate the function of the endocrine glands using the nuclear medicine approach.