Showing papers in "Endocrine Reviews in 1996"
TL;DR: At the beginning of the second half of the 20th century, most efforts were directed at understanding the molecular and cellular basis of the immune response and the mechanisms of acquisition of immunologic responses.
Abstract: I. Introduction THE existence of mechanisms that provide immunity to an infective agent was inferred from empirical observations obtained through the ingenuity and deductive capacity of early investigators. The first procedures for vaccinations and serotherapy resulted from these observations. The implementation of these procedures, probably the most important contribution of immunology to medical science, was, at first, based on a very rudimentary knowledge of the immune system. During the first half of the 20th century, this rather primitive knowledge coincided with evidence showing that the endocrine and nervous systems integrate and regulate different bodily functions. Therefore, based on some supportive data, it was considered that immune mechanisms may also be influenced by these systems. However, at the beginning of the second half of the 20th century, most efforts were directed at understanding the molecular and cellular basis of the immune response and the mechanisms of acquisition of immunologic...
1,472 citations
TL;DR: A picture has emerged depicting the classic endocrine control of ovarian function by LH and FSH, entangled in a maze of regulatory systems hinging on cell-cell interactions between follicular cells, via action of a variety of molecules.
Abstract: I. Introduction IN THE adult ovary, folliculogenesis starts when follicles leave the pool of resting follicles (RF) to enter the growth phase. From there, the early growing follicle undergoes a developmental process including a dramatic course of cellular proliferation and differentiation. In primates, only one follicle commonly reaches the preovulatory stage every cycle; most follicles fail to complete this maturation scheme, dying in the process termed atresia. In recent years, a picture has emerged depicting the classic endocrine control of ovarian function by LH and FSH, entangled in a maze of regulatory systems hinging on cell-cell interactions between follicular cells, via action of a variety of molecules (1–3). Different types of cell-cell interactions have been described. In paracrine regulations, a molecule synthesized by one cellular type is released into the interstitial milieu to act directly on another cellular type. In autocrine regulations, molecules synthesized by one cellular type are rel...
1,410 citations
TL;DR: IGFs can be viewed as extracellular second messengers that mediate most, if not all, such actions of agents that stimulate cell proliferation, in contrast to the relatively large number of growth factors that inhibit the process.
Abstract: It is very clear that the GH-IGF axis plays a major role in controlling the growth and differentiation of skeletal muscles, as it does virtually all of the tissues in the animal body. One aspect of this control is unquestioned: circulating GH acts on the liver to stimulate expression of the IGF-I and IGFBP3 genes, substantially increasing the levels of these proteins in the circulation. It also seems that GH stimulates expression of IGF-I genes in skeletal muscle, although there are a number of cases in which skeletal muscle IGF-I expression is elevated in the absence of GH. It is substantially less clear that GH acts directly on skeletal muscle to stimulate its growth; the presence of GH receptor mRNA in skeletal muscle is well established, but most investigators have been unsuccessful in demonstrating any specific binding of GH to skeletal muscle or to myoblasts in culture. It has been equally difficult to show direct actions of GH on cultured muscle cells; the only positive report concludes that the early insulin-like effects of GH can result from direct interactions between GH and isolated muscle cells. The effects of the IGFs on skeletal muscle are much clearer. It is well established by studies in a number of laboratories on a variety of systems that IGFs stimulate many anabolic responses in myoblasts, as they do in other cell types. IGFs have the unusual property of stimulating both proliferation and differentiation of myoblasts, responses that are generally believed to be mutually exclusive; in myoblasts, they are in fact temporally separated. The stimulation of differentiation by IGF-I is (at least in part) a result of substantially increased levels of the mRNA for myogenin, the member of the MyoD family most directly associated with terminal myogenesis. As levels of myogenin mRNA rise, those of myf-5 mRNA (the only other member of the MyoD family expressed significantly in L6 myoblasts) fall dramatically, although myf-5 expression is required for the initial elevation of myogenin. The effects of IGFs are significantly modulated by IGFBPs secreted by myoblasts in serum-free medium, inhibitory IG-FBPs-4 and -6 are expressed and secreted by L6A1 myoblasts, while expression of IGFBP-5 rises dramatically as differentiation proceeds. Other myoblasts also secrete IGFBP-2. Even if exogenous IGFs are not added to the low-serum "differentiation" medium, myoblasts express sufficient amounts of autocrine IGF-II to stimulate myogenesis after a period of time; some myogenic cell lines, (such as Sol 8) are so active in expressing the IGF-II gene that it is not possible to demonstrate effects of exogenous IGFs. This autocrine expression of IGFs is by no means unique to skeletal muscle cells; indeed, it is so widely seen in cells responding to mitogenic stimuli that we suggest that IGFs can be viewed as extracellular second messengers that mediate most, if not all, such actions of agents that stimulate cell proliferation. The component of serum that suppresses IGF-II gene expression under "growth" conditions appears to be the IGFs themselves, which exhibit a very high potency in the feedback inhibition of IGF-II expression. In addition, IGFs have effects on the expression of other genes related to differentiation. Treatment of L6A1 cell with IGFs suppresses their expression of the myogenesis-inhibiting TGF beta s with a time course consistent with an initial proliferative step followed by differentiation, i.e. expression is first increased and then very substantially decreased. It is not established that this plays a role in control of differentiation, but experiments with FGF antisense constructs suggests that this may well be the case. Until recently, IGFs were the only circulating agents known to stimulate myoblast differentiation, in contrast to the relatively large number of growth factors that inhibit the process. It is now clear that thyroid hormones and RA also stimulate myogenesis, and that IL-15 enhances the stimulatory eff
1,138 citations
TL;DR: This chapter will focus on studies designed to elucidate the mechanisms involved in the acute regulation of steroid production in response to hormone stimulation.
Abstract: The mechanism regulating the production of steroids in response to trophic hormone stimulation has been the subject of investigation for over three decades. When considering the effects of trophic hormones on the steroidogenic process it is necessary to first distinguish between acute effects and chronic effects. Acute effects are those which result in the very rapid (within minutes) synthesis and secretion of steroids in response to hormone stimulation and involve the rapid translocation of intracellular cholesterol to the site of its cleavage, as will be discussed later. Chronic effects are those which occur on the order of hours to tens of hours and involve increased gene transcription and translation of the proteins involved in the biosynthesis of steroids. This chapter will focus on studies designed to elucidate the mechanisms involved in the acute regulation of steroid production in response to hormone stimulation. Overviews of the effects of chronic stimulation on steroidogenic enzymes have appeared in several excellent review articles (Simpson and Waterman 1983; Miller 1988; Hanukoglu 1992).
1,055 citations
TL;DR: This review has summarized the multiple endogenous and exogenous factors that have been shown to be involved in this signaling cascade and, thus, to alter glucocorticoid sensitivity.
Abstract: I. Introduction STEROID hormones are essential constituents of the intercellular communication system that maintains homeostasis in higher organisms. Glucocorticoids, a major subclass of steroid hormones, modulate a large number of metabolic, cardiovascular, immune, and behavioral functions (for a review see Refs. 1 and 2). Glucocorticoids are produced by the adrenal cortex under the regulatory influence of ACTH. The latter is produced by corticotrophs of the anterior pituitary, in turn, under the regulatory influence of hypothalamic CRH and arginine vasopressin (AVP). The hypothalamic-pituitary-adrenal (HPA) axis is kept in balance by the negative feedback effects of cortisol on the secretion of ACTH, CRH, and usually, to a lesser extent, AVP. In the resting state, basal levels of CRH, AVP, ACTH, and cortisol are released in a pulsatile and circadian fashion. At these baseline levels, the main function of cortisol is to sustain normoglycemia and to prevent arterial hypotension. Whether and to what extent...
930 citations
TL;DR: It is shown that antidepressants interfere not only with the production and release of catecholamines and indolamines but also with the signal transduction of those neurotransmitters that have long been implicated in the pathogenesis and treatment of depression.
Abstract: I. Introduction PAST studies of antidepressants have focused almost exclusively on their effects on the metabolism and receptors of monoamine neurotransmitters in various brain regions. These studies have been extended to the molecular effects of antidepressants and have led to a profoundly expanded understanding of their actions in the central nervous system. For example, long-term administration of antidepressants decreases the expression of tyrosine hydroxylase, down-regulates cAMP-dependent protein kinase, modulates the mRNA expression of central β-adrenoceptors and serotonin (5-HT) receptors, and alters the functional activity of specific G protein subunits and adenylyl cyclase (1). Taken together, these and many other recent observations clearly indicate that antidepressants interfere not only with the production and release of catecholamines and indolamines but also with the signal transduction of those neurotransmitters that have long been implicated in the pathogenesis and treatment of depression...
859 citations
TL;DR: This review addresses the concept of the dual function of PRL, as a circulating hormone and a cytokine, based on its shared properties with hematopoietic growth factors.
Abstract: I. Introduction PRL affects more physiological processes than all other pituitary hormones combined. Among these are the regulation of mammary gland development, initiation and maintenance of lactation, immune modulation, osmoregulation, and behavioral modification. At the cellular level, PRL exerts mitogenic, morphogenic, or secretory activities. This raises the question as to the mechanism by which a single hormone can modulate so many seemingly unrelated functions. This review addresses the concept of the dual function of PRL, as a circulating hormone and a cytokine. The diversity of PRL actions is derived from three components: structural polymorphism, local production and processing, and divergent intracellular signaling pathways and target genes. PRL can be easily classified as a cytokine based on its shared properties with hematopoietic growth factors. These include comparable structural motifs, multiple sites of synthesis, ubiquitous receptor distribution, homologous receptor structure, and simila...
703 citations
TL;DR: The effects of gonadal steroids on the function of the normal immune system as well as their impact on autoimmune processes are examined and current knowledge of the cellular and molecular mechanisms by which Gonadal Steroid effects on Immunity are explored.
Abstract: I. Introduction THE remarkable female predominance of such diverse autoimmune diseases as systemic lupus erythematosus (SLE), Hashimoto's thyroiditis, rheumatoid arthritis, and primary biliary cirrhosis has suggested to many clinicians that hormonal differences between the sexes must confer some protective effect on males or enhance the susceptibility of females to these diseases. This review will examine the evidence in support of such an hypothesis. We will examine the effects of gonadal steroids on the function of the normal immune system as well as their impact on autoimmune processes. We will explore current knowledge of the cellular and molecular mechanisms by which gonadal steroids might modulate both normal and disordered function of the immune system. II. Physiology and Pathophysiology of Gonadal Steroid Effects on Immunity A. Normal immune responses are sexually dimorphic A significant body of data establishes that a number of aspects of immune responsiveness normally differ between males and fe...
692 citations
TL;DR: Major advances have been made recently in the understanding of the cell biology and molecular biology of the osteoclast, as well as the role that the marrow microenvironment plays in regulating osteOClast formation and bone resorption.
Abstract: I. Introduction BONE is a dynamic tissue that constantly undergoes remodeling. Bone remodeling is a coupled process in which bone resorption is normally followed by new bone formation. During early life, bone formation exceeds bone resorption with a net increase in bone mass, while late in life, bone resorption exceeds bone formation with net loss of bone. During some pathological processes, such as in patients with advanced stages of multiple myeloma, bone remodeling is uncoupled, and bone resorption is not followed by new bone formation. The primary cell responsible for bone resorption is the multinucleated osteoclast. Although many questions still remain unanswered about the factors that regulate osteoclast formation and osteoclastic bone resorption, major advances have been made recently in our understanding of the cell biology and molecular biology of the osteoclast, as well as the role that the marrow microenvironment plays in regulating osteoclast formation and bone resorption.
519 citations
TL;DR: Bone markers can be used for a variety of important purposes: as tools for basic bone biology research, for defining general physiological phenomenon in clinical studies or drug trials, and for following individual patients.
Abstract: An ideal battery of tests would include indices of bone resorption and formation. They should be unique to bone, reflect total skeletal activity, and should correlate with traditional measures of bone remodeling activity, such as radiocalcium kinetics, histomorphometry, or changes in bone mass. Factors that confound their measurement, such as circadian rhythms, diet, age, sex, bone mass, liver function, and kidney clearance rates, should be clearly defined (Fig. 9). To date, no bone marker has been established to meet all these criteria, and each marker may have its own specific advantages and limitations. There are still questions that must be answered before there can be complete confidence in the information gained from measurement of any of the bone markers. Furthermore, it should be emphasized that none of the markers are diagnostic for any particular bone disease and cannot be used for this purpose in individual patients. Nevertheless, recent advances in research and development have provided assays with increased specificity, sensitivity, and availability. Because of this, bone markers can be used for a variety of important purposes: as tools for basic bone biology research, for defining general physiological phenomenon in clinical studies or drug trials, and for following individual patients.
508 citations
TL;DR: This work has shown that alternative tissue-specific processing of primary mRNA from the α-CT/CGRP gene in rats generates two distinct peptides, CT and CGRP, which are the most potent endogenous vasodilatory peptides that have been discovered.
Abstract: I. Introduction THE calcitonin (CT) and calcitonin gene-related peptide (CGRP) are derived from the CT/CGRP gene, which is localized in chromosome 11. Alternative splicing of the primary RNA transcript leads to the translation of CGRP and CT peptides in a tissue-specific manner. This alternative tissue-specific processing of primary mRNA from the α-CT/CGRP gene in rats generates two distinct peptides, CT and CGRP (1, 2). CGRP is a 37-amino acid neuropeptide expressed predominantly in the nervous system and CT is expressed mainly in the thyroid gland. CGRP receptors, widely distributed in the body, are the most potent endogenous vasodilatory peptides that have been discovered. Derived from the C cells of the thyroid gland, CT is the most potent peptide inhibitor of osteoclast-mediated bone resorption and is involved primarily in protecting the skeleton during periods of “calcium stress” such as growth, pregnancy, and lactation (3). In 1961, Copp and colleagues (4) postulated the existence of the calcium-lo...
TL;DR: One important message to remember is that whenever a patient has evidence of a pituitary tumor, a serum T4 and TSH level must be obtained, and the dramatic reduction in pituitsary size and resolution of endocrine dysfunction with thyroid hormone is gratifying.
Abstract: I. Introduction The term “TSH-secreting pituitary tumors” includes two opposite clinical conditions: true thyrotroph neoplasia that results in secondary hyperthyroidism, also called “central hyperthyroidism,” and pituitary hyperplasia resulting from longstanding primary hypothyroidism. The latter condition was first recognized 145 yr ago (1), while the former was not clearly identified until the RIA era (2–8). However, in the 1950s and 1960s, while it became clear that Graves' disease was not caused by hyperpituitarism (9, 10), scattered reports suggested a possible association between pituitary tumors and hyperthyroidism (11–15), although no measurement of TSH levels was available during this time. The first case of TSH-secreting pituitary adenoma (TSH-oma) was documented in 1960 by measuring serum TSH levels with a bioassay (16). In 1970, Hamilton et al. (17) reported the first case of TSH-oma proved by a RIA that was much more sensitive and specific than the previously used bioassays. Classically, TSH-...
TL;DR: In a given cell type, the responsiveness to stimulus, as well as the nature of the response, is dictated by the available complement of receptor, G protein, and effector.
Abstract: I. Introduction RECEPTORS coupled to heterotrimeric GTP-binding proteins (G proteins) comprise the largest known family of cell surface receptors and mediate cellular responses to a diverse array of signaling molecules, including peptide and glycopeptide hormones, neurotransmitters, phospholipids, odorants, and photons. The basic unit of G protein-coupled receptor (GPCR) signaling is comprised of three parts; receptor, which detects ligand in the extracellular milieu; heterotrimeric G protein, which is dissociated into active Gα-GTP and Gβγ-subunits after interaction with the liganded receptor; and effector, which interacts with dissociated Gα-GTP and Gβγ-subunits to mediate the intracellular effects of ligand binding. In a given cell type, the responsiveness to stimulus, as well as the nature of the response, is dictated by the available complement of receptor, G protein, and effector. Despite the diverse array of ligands with which they interact, GPCRs share a conserved predicted tertiary structure char...
TL;DR: Interactions of the receptors with components of the basal transcriptional machinery and with sequence-specific transcription factors the authors show how steroid hormones modulate the activity of various genes in target cells through binding to intracellular receptors.
Abstract: I. Introduction REGULATION of gene expression by steroid hormones is a traditional field of molecular endocrinology. The hormones act by binding to intracellular receptors, which themselves orchestrate the transcriptional response. After the cloning of the hormone receptors and the identification of their target sequences on DNA at the end of the 1980s, the question of how steroid hormones modulate the activity of various genes in target cells seemed to be solved. It was clear that steroid hormone receptors are ligand-activated transcriptional modulators, which in most cases act through binding to specific sequences on DNA called hormone-responsive elements (HREs) (1). Careful mutational analysis identified a modular structure of the receptors composed of a DNA-binding domain, nuclear localization signals, a ligand-binding domain, and several transactivation domains (2). Interactions of the receptors with components of the basal transcriptional machinery and with sequence-specific transcription factors we...
TL;DR: A growing number of studies has provided strong evidence that fetal membranes (amnion, chorion) and maternal decidua are capable of hormone production and metabolism and, when containing hormonal receptors, serve as endocrine organs.
Abstract: I. Introduction During the last 15 years our concepts of the role and functioning of intrauterine tissues during human pregnancy have been changing. While initially considered solely for their role in the exchange of gas and transfer of nutrients and waste, recent studies emphasize the contribution of placenta, decidua, and amnion-chorion to gestational development. Indeed, starting in the 1970s, evidence that human placenta is able to produce hormones, cytokines, and growth factors greatly expanded our knowledge of the functioning of intrauterine tissues and their putative roles in the physiology of pregnancy. A growing number of studies has provided strong evidence that fetal membranes (amnion, chorion) and maternal decidua are capable of hormone production and metabolism and, when containing hormonal receptors, serve as endocrine organs (Fig. 1). Intrauterine tissues are a source of brain, pituitary, gonadal, and adrenocortical peptide and steroid hormones, chemically identical to and biologically acti...
TL;DR: The present review will deal specifically with the putative role of PACAP as a hypophysiotropic factor regulating anterior pituitary cell activity.
Abstract: I. Introduction PITUITARY adenylate cyclase activating polypeptide (PACAP) was first isolated from ovine hypothalamus by its potent activity in stimulating cAMP production in rat anterior pituitary cells (1). Since its isolation a wealth of literature has been published describing its activity in a variety of tissues including pituitary, brain, adrenal, testis, and in the nerve fibers of both the gut and the lung. A number of reviews have discussed its actions in a variety of cell types (2–4), its binding sites (5), and the characteristics of the three PACAP receptors cloned to date, two of which it apparently shares with vasoactive intestinal polypeptide (VIP) (4, 6, 7). The present review will deal specifically with the putative role of PACAP as a hypophysiotropic factor regulating anterior pituitary cell activity: This review begins with a brief history of PACAP and a description of its structure and its receptors. We will then discuss the distribution of PACAP in the hypothalamus, which suggests its r...
TL;DR: It is now assumed that primatePLs evolved from the GH lineage while nonprimate PLs arose from the PRL/GH precursor gene.
Abstract: I. Introduction PRL PL, and GH are homologous proteins that are thought to have arisen from a common ancestral gene by two successive tandem duplications (Refs. 1–5; for review, see Ref. 6). PRL and GH are mainly secreted by the anterior pituitary of all vertebrates. The divergence of the PRL and GH lineage from the common ancestral gene has been located some 400 million years ago, which is in good agreement with the presence of distinct PRL and GH in fish (2, 3, 6, 7). PL is uniquely observed in mammals and is secreted in the placenta by syncytiotrophoblastic cells (for reviews, see Refs. 8–10). Initially, PLs were proposed to have evolved from the common PRL/GH precursor gene (1). Further cloning and analysis of PRL, GH, and PL genes from different species (chromosome carrier, gene size, splicing sites, sequence identity; see Refs. 6, 7, 11, and 12) have led to a reconsideration of this hypothesis, and it is now assumed that primate PLs evolved from the GH lineage while nonprimate PLs arose from the PRL...
TL;DR: Thyroid hormone metabolism normalizes with renal transplantation; however, glucocorticoid therapy may induce additional changes, and patients with hyperthyroidism or follicular neoplasms require reduced dosages of Na 131-I depending upon type, frequency, and duration of dialysis therapy.
Abstract: I. Introduction END-STAGE renal disease (ESRD) is a relatively common nonthyroidal illness, which induces significant morbidity and mortality (1). In the United States, more than 220,000 patients were being dialyzed for ESRD in 1992, with an 8–9% annual increase in frequency over the last 10 years (1, 2). This rising incidence of ESRD reflects improved survival rates of ESRD patients and increasing age of the general population, with the greatest increase in ESRD frequency being in people over 64 yr of age (2). ESRD is a moderate to severe nonthyroidal illness and, as such, frequently alters thyroid hormone metabolism (3). In addition to metabolic and endocrine derangements induced by ESRD, these patients frequently have a multitude of nonrenal nonthyroidal disorders that affect thyroid hormone metabolism, including diabetes mellitus (1), infections (1), and malnutrition (4–6), and they are treated by a variety of pharmacological agents. Knowledge of alterations of thyroid hormone metabolism in euthyroid ...
TL;DR: The recent cloning of a [Ca2+]o-sensing receptor from several different tissues in several species directly demonstrates that a variety of cells can directly recognize and respond to small changes in their ambient level through a G protein-coupled, cell surface receptor.
Abstract: The recent cloning of a [Ca2+]o-sensing receptor from several different tissues in several species directly demonstrates that a variety of cells can directly recognize and respond to small changes in their ambient level of [Ca2+]o through a G protein-coupled, cell surface receptor. This finding directly documents that [Ca2+]o can act as an extracellular, first messenger in addition to subserving its better known role as an intracellular second messenger. Several of the tissues expressing the CaR are important elements in the calcium homeostatic system that have long been known to be capable of sensing [Ca2+]o, such as parathyroid and thyroidal C cells. The presence of the receptor in the kidney, however, provides strong evidence that several of the long-recognized but poorly understood direct actions of [Ca2+]o on renal function could be mediated by the CaR. These actions include the up-regulation of urinary calcium and magnesium excretion in the setting of hypercalcemia, which complements the indirect inhibition of renal tubular reabsorption of calcium that results from high [Ca2+]o-mediated inhibition for PTH secretion. The impaired renal concentrating capacity in hypercalcemia is likely a manifestation of a homeostatically important interaction between the regulation of renal calcium and water handling that reduces the risk of pathological deposition of calcium in the kidney when there is a need to dispose of excess, calcium in the urine. In this regard, the availability of human syndromes of [Ca2+]o "resistance" or "overresponsiveness" due to loss-of-function or gain-of-function mutations in the CaR, respectively, have provided useful experiments in nature that have clarified the importance of the receptor in both abnormal and normal physiology. Much remains to be learned, however, about the role of the CaR in locations, such as the brain, where it likely responds to local rather than systemic levels of [Ca2+]o. In such sites, it may represent an important modulator of neuronal function, responding to [Ca2+]o as a neuromodulator or even neurotransmitter. The development of therapeutics that either activate or inhibit the function of the CaR may be useful for treating a variety of conditions in which the receptor is either under- or overactive. Finally, it would not be surprising to discover additional receptors for [Ca2+]o or for other ions (the CaR may, in fact, be an important [Mg2+]o-sensor) that could function abnormally in certain disease states and be amenable to pharmacological manipulation with ion receptor-based therapeutics.
TL;DR: The sequential studies of stable ald testosterone levels despite decreased aldosterone response to ACTH stimulation indicate that alterations in response to provocative testing do not predict the development of hormonal insufficiency in this patient population.
Abstract: Numerous alterations in endocrine function are observed in HIV infection. Direct destruction of endocrine organs by HIV itself or by invasive infection with opportunistic organisms resulting in loss of function is rare. When acutely ill, HIV patients can develop the metabolic derangements that accompany any severe systemic disorder. Studies of thyroid function tests emphasize that the presence of acute secondary infection must be analyzed when evaluating such patients. In addition to euthyroid sick syndrome other hormonal axes are affected by severe illness. These alterations may be cytokine mediated. As with seronegative patients, these changes can be transient and resolve with successful treatment of the intervening illness. Given the complexity of HIV disease, future reports should characterize patients by CD4 cell count, history of AIDS-indicating illnesses, and viral load. Viral burden is an independent predictor of immunosuppression and progression to AIDS. A large number of medications used in the treatment of HIV infection and related illnesses can alter endocrine function, mineral and electrolyte balance, and substrate turnover. Drug therapy must be considered in the evaluation of endocrine abnormalities in HIV-infected patients and carefully characterized in studies of these patients. The endocrine effects of medications used in the treatment of HIV infection are summarized in Table 3. Concomitant factors that affect endocrine function independent of the HIV virus can confound results in these patients. For example, opiate use affects PRL, gonadotropins, and cortisol response to ACTH stimulation. Investigations in HIV-infected patients must include careful descriptions of the study population and comparison to relevant controls. HIV-infected patients may also demonstrate more subtle alterations in endocrinological function in early, relatively asymptomatic, stages. The etiology and clinical significance of these changes, particularly their relationship to cytokines, continues to be investigated. The sequential studies of stable aldosterone levels despite decreased aldosterone response to ACTH stimulation indicate that alterations in response to provocative testing do not predict the development of hormonal insufficiency in this patient population. Similar longitudinal studies need to be done for the other hormonal axes to further delineate the endocrinological alterations in HIV infection. Finally, when the rationale for hormone replacement is debatable, double-blind, placebo-controlled studies are necessary. Transient improvement in clinical status during open-label treatment does not prove hormone insufficiency. The long-term efficacy and safety of hormonal therapy must be demonstrated.
TL;DR: GH receptors, IGFs, and IGF-receptors are expressed in the kidney, and their location in the different parts of the nephron suggests autocrine or paracrine as well as endocrine modes of action.
Abstract: GH receptors, IGFs, and IGF-receptors are expressed in the kidney. Their location in the different parts of the nephron suggests autocrine or paracrine as well as endocrine modes of action. A lack of GH receptors and probably of IGF-I synthesis in glomeruli in vivo suggest that all glomerular GH and IGF-I effects are mediated by circulating IGF-I through endocrine modes. GH and IGF-I increase GFR in normal rats and humans, and increase phosphate and possibly sodium reabsorption in normal and diabetic subjects. During normal renal development GH, IGF-I, and IGF-II appear to play a role. GH and IGF-I cause kidney growth, and circulating and/or renal IGF-I appear to contribute to renal hypertrophy and compensatory renal growth in experimental animal models. GH may contribute also to glomerular sclerosis and progression of renal failure in experimental models. In patients with chronic renal failure such a role of endogenous or exogenous GH has not yet been convincingly proven. In chronic or acute renal failure and in the nephrotic syndrome there are complex abnormalities in the systemic and renal IGF/IGFBP-system. In chronic renal failure there is resistance to GH and IGF-I that can be overridden by pharmacological administration of each of the peptides. GH is used therapeutically in children with chronic renal failure to accelerate growth. GH and IGF-I may be useful agents to improve nitrogen balance and nutritional status in patients with chronic renal failure. In rats with ARF, administration of IGF-I accelerates the recovery of renal function. Whether this treatment is also successful in patients with ARF remains to be demonstrated by ongoing clinical trials.
TL;DR: In addition to their role as adhesion receptors, integrins also function as signaling receptors and have been shown to regulate reorganization of the cytoskeleton, intracellular ion transport, lipid metabolism, and cell surface receptors.
Abstract: I. Introduction INTEGRINS are a family of more than 20 different transmembrane receptors composed of noncovalently associated α- and β-subunit heterodimers (1). Twelve different α-subunits, each approximately 1000 residues in length, and eight different β-subunits, each approximately 750 residues, have been identified. The receptor consists of a very large extracellular domain, a transmembrane region, and a relatively short cytoplasmic region. The extracellular domain binds to various ligands including extracellular matrix (ECM) proteins, such as fibronectin (FN), vitronectin (VN), and collagen (Col), and to other cell surface receptors such as ICAM-1 (intercellular adhesion molecule) and VCAM-1 (vascular cell adhesion molecule). The receptor cytoplasmic domains interact with cytoskeletal proteins. In addition to their role as adhesion receptors, integrins also function as signaling receptors and have been shown to regulate reorganization of the cytoskeleton, intracellular ion transport, lipid metabolism,...
TL;DR: Hormonal testing shows an increased secretion of cortisol, which is not suppressed by the overnight dexamethasone test, and in patients with chronic alcohol abuse, clinical or biochemical features or both of Cushing's syndrome can be found.
Abstract: I. Introduction Cushing's syndrome is clinically characterized by truncal obesity, moon face, supraclavicular fat pads, buffalo hump, hirsutism, blue-red striae, easy bruisability, osteoporosis, hypertension, and proximal myopathy. Biochemically, impaired glucose tolerance and hypokalemic alkalosis can be present. Leukocytosis with lymphocytopenia and decreased numbers of eosinophils are often found. Hormonal testing shows an increased secretion of cortisol, which is not suppressed by the overnight dexamethasone test (1 mg). Depending on the etiology of the syndrome, decreased or increased secretion of ACTH is found. In patients with chronic alcohol abuse, clinical or biochemical features or both of Cushing's syndrome can be found. Because both the physical and the hormonal abnormalities disappear after discontinuation of alcohol this phenomenon was called alcohol-induced pseudo-Cushing's syndrome (1, 2). Alcohol-induced pseudo-Cushing's syndrome is indistinguishable from true Cushing's syndrome, although...
TL;DR: This review will focus on three axes: pituitary-adrenal, entero-pancreatic, and GH, which can provide important insights into the structure-function and physiological relationships in these axes.
Abstract: I. Introduction THE guinea pig, a New World hystricomorph, is one of the most commonly used laboratory animals and, as a consequence, much information has accrued detailing its biochemical characteristics. This information remained relatively inaccessible until a decade ago, when a partial checklist of the comparative biochemistry of the guinea pig was compiled by Wriston (1). Since then, it has become apparent that the guinea pig has a number of anomalies in its endocrine axes and metabolic pathways which may not only be of interest to those working with the guinea pig as an animal model, but which, by comparison with other species, including humans, can provide important insights into the structure-function and physiological relationships in these axes. This review will focus on three axes: pituitary-adrenal, entero-pancreatic, and GH. These axes and the components that have been characterized at a structural level are listed in Table 1; their various interactions are shown schematically in Fig. 1.
TL;DR: There is now ample evidence that cytoskeletal fibers play a pivotal role in cell motility and various forms of intracellular movements including axonal transport, chromosome migration, and pigment dispersion.
Abstract: I. Introduction THE cytoskeleton is formed by three types of high molecular weight polymers, namely microtubules, microfilaments, and intermediate filaments. Microtubules and microfilaments are homogeneous and ubiquitous structures (1), whereas intermediate filaments represent a heterogeneous family of fibers whose expression depends upon the level of differentiation of the cells (2–4). All three types of cytoskeletal elements are intimately associated with cytoplasmic organelles, particularly mitochondria (5–7), lysosomes (8, 9), and secretory vesicles (10, 11). Microtubules, microfilaments, and intermediate filaments also interact with the nucleus (12–14), the plasma membrane (15, 16), and, indirectly, with the extracellular matrix (17–19). There is now ample evidence that cytoskeletal fibers play a pivotal role in cell motility (20–23) and various forms of intracellular movements including axonal transport (24, 25), chromosome migration (26–28), and pigment dispersion (29, 30). Cytoskeletal components ...
TL;DR: The role of steroidal feedback between ovary, pituitary, and hypothalamus has been known for many years, and knowledge of the mechanisms involved continues to expand, and recent reviews of a novel ovarian factor have supported the evidence for its existence.
Abstract: I Introduction REGULATION of the ovarian cycle is by a complex series of positive and negative feedback mechanisms between ovary, hypothalamus, and pituitary The role of steroidal feedback between ovary, pituitary, and hypothalamus has been known for many years, and our knowledge of the mechanisms involved continues to expand Nonsteroidal ovarian secretagogues also have endocrine regulatory function, some acting centrally The best known of these is inhibin, although its central function is now uncertain Since the late 1970s it has become evident that there are ovarian nonsteroidal products with specific inhibitory effects on pituitary responsiveness to GnRH As early as 1979 (1) it was suggested that follicular fluid contained a factor other than inhibin that suppressed GnRH-induced LH secretion in vitro Recent reviews of a novel ovarian factor, which has been called gonadotropin surge-attenuating factor (GnSAF) or gonadotropin surge-inhibiting factor (GnSIF), have supported the evidence for its exi