Showing papers in "Trends in Endocrinology and Metabolism in 1991"
TL;DR: The photoperiodic message that the pineal gland conveys to the organism is encoded in the circadian melatonin rhythm, a ubiquitously acting hormone that mediates seasonal changes in reproduction in nonhuman mammals and may have reproductive consequences in humans as well.
Abstract: The photoperiodic message that the pineal gland conveys to the organism is encoded in the circadian melatonin rhythm. Melatonin is a ubiquitously acting hormone that mediates seasonal changes in reproduction in nonhuman mammals and may have reproductive consequences in humans as well. Additionally, melatonin may relate to the function o f the immune system, hormone-responsive tumor growth, circadian rhythm disturbances, and a number of other processes.
189 citations
TL;DR: Insulinlike growth factors, their binding proteins, and receptors are expressed by many different tissues, suggesting that they may act as parts of an autocrine paracrine system in addition to having a classic endocrine role.
Abstract: Insulinlike growth factors (IGFs), their binding proteins, and receptors are expressed by many different tissues, suggesting that they may act as parts of an autocrine paracrine system in addition to having a classic endocrine role. Since these growth factors are essential for the normal growth and development of the organism, their altered rate of production in a number of important disease states results in severe growth alterations. These include nutritional deprivation, growth hormone deficiency, diabetes, and malignancy.
102 citations
TL;DR: Because the brain regulates the endocrine system and also responds to it, the changing environment as well as the experiences of the animal can change and shape properties of hormone-sensitive nerve cells.
Abstract: Because the brain regulates the endocrine system and also responds to it, the changing environment as well as the experiences of the animal can change and shape properties of hormone-sensitive nerve cells. Depending upon the physiologic status of the organism, the effects of actions of steroid hormones can be trophic or damaging to the nervous system. Future research on the actions of steroids on the brain may advance the notion that the endocrine system has some responsibility for determining the individual traits of an animal in brain function and behavior.
85 citations
TL;DR: Vasoactive intestinal polypeptide (VIP), a neuropeptides with wide distribution in the central and peripheral nervous systems, has a broad spectrum of biologic actions and may be an important factor in the pathogenesis of several diseases.
Abstract: Vasoactive intestinal polypeptide (VIP), a neuropeptide with wide distribution in the central and peripheral nervous systems, has a broad spectrum of biologic actions. Usually acting as a neurotransmitter or neuromodulator but sometimes also as a blood-borne hormone, it participates in the regulation of a variety of major body functions and may be an important factor in the pathogenesis of several diseases.
71 citations
TL;DR: Congenital adrenal hypoplasia with gonadotropin deficiency is a rare X-linked recessive disorder that usually manifests with symptoms of adrenal insufficiency early in infancy, and considerations of genetic heterogeneity, possible chromosomal abnormalities, and prenatal diagnostic studies warrant medical genetic evaluations.
Abstract: Congenital adrenal hypoplasia with gonadotropin deficiency is a rare X-linked recessive disorder that usually manifests with symptoms of adrenal insufficiency early in infancy. Adequate replacement therapy with glucocorticoids, mineralocorticoids, and salt has resulted in an increased survival. Slow growth and failure to undergo sexual maturation during the adolescent years usually ensues, secondary to hypogonadotropic hypogonadism. The X-linked congenital adrenal hypoplasia locus has been mapped to region Xp21.3-p21.2. Interstitial deletions of the X chromosome overlapping this region have been observed to cause complex clinical problems, with adrenal hypoplasia as a prominent component. Within a family segregating the disease, there is a 50% risk of having an affected male and a 50% risk of having a carrier female; considerations of genetic heterogeneity, possible chromosomal abnormalities, and prenatal diagnostic studies warrant medical genetic evaluations. The following case presentations illustrate the clinical spectrum of this condition.
69 citations
TL;DR: The implications of recent discoveries concerning hsp90 (heat-shock protein M(r) approximately 90,000)-receptor interaction, receptor-DNA binding, and the involvement of transcription factors in the mechanism of action of RU486 are discussed.
Abstract: RU486 is a very powerful antisteroid hormone compound, with antiprogestin and antiglucocorticosteroid clinical applications. High-affinity binding to the receptor ligand-binding domain results in essentially antagonistic function; however, some agonistlike effects have been observed. This review discusses the implications of recent discoveries concerning hsp90 (heat-shock protein M(r) approximately 90,000)-receptor interaction, receptor-DNA binding, and the involvement of transcription factors in the mechanism of action of RU486.
57 citations
TL;DR: Paget's disease of bone is a common disorder of older patients that may sometimes cause a variety of signs and symptoms referable to the skeleton, and typically the serum alkaline phosphatase level and total urinary hydroxyproline excretion are elevated.
Abstract: Paget's disease of bone is a common disorder of older patients that may sometimes cause a variety of signs and symptoms referable to the skeleton. An intrinsic bone-remodeling abnormality in this disease may lead to bone deformity, pain, and various arthritic or neurologic complications. Characteristic radiographic changes can be seen, and typically the serum alkaline phosphatase level and total urinary hydroxyproline excretion are elevated. Current therapies that interfere with excess osteoclast activity are helpful in many cases, but treatment choices and expected responses must be considered in the context of the individual patient.
51 citations
TL;DR: The hypertriglyceridemia of infection is produced by many of the cytokines that regulate the immune response, including the tumor necrosis factors, interleukin-1, interferons, and the interferon.
Abstract: The hypertriglyceridemia of infection is produced by many of the cytokines that regulate the immune response, including the tumor necrosis factors, interleukin-1, interleukin-6, and the interferons. In rodents, this hypertriglyceridemia is primarily due to the ability of these cytokines to stimulate hepatic lipogenesis and very low density lipoprotein production without causing significant changes in adipose tissue lipoprotein lipase or triglyceride clearance. Induction of hypertriglyceridemia is not directly linked to the syndrome of wasting. Rather, the increase in hepatic production of lipoproteins is part of the acute-phase response and may contribute to host defense.
46 citations
TL;DR: AMH assays and genetic studies now provide meaningful information regarding testicular function in infancy and the molecular basis of a rare form of male pseudohermaphroditism, the persistent Müllerian duct syndrome.
Abstract: Anti-Mullerian hormone (AMH), alias Mullerian-inhibiting substance or factor, plays a key role in fetal sex differentiation. The cloning of the human gene, a member of the transforming growth-factor-beta family and the development of immunochemical reagents recognizing circulating human AMH have opened new perspectives for clinical research. AMH assays and genetic studies now provide meaningful information regarding testicular function in infancy and the molecular basis of a rare form of male pseudohermaphroditism, the persistent Mullerian duct syndrome.
45 citations
TL;DR: Evidence is presented to suggest thatterior pituitary cells that contain adrenocorticotropin are multipotential cells with the capacity to augment corticotropes or one of the other cell populations.
Abstract: Anterior pituitary cells that contain adrenocorticotropin (ACTH) are morphologically and functionally heterogeneous. Immunolabeling has identified stellate subtypes with scattered or peripherally arranged granules, and ovoid or irregularly shaped cells with a denser accumulation of granules, which overlap morphologically with other cell types such as small gonadotropes or thyrotropes. Dual cytochemical labeling studies on the same or serial fields have identified cells that store ACTH with LH, FSH, TSH, or prolactin. Evidence is presented to suggest that they are multipotential cells with the capacity to augment corticotropes or one of the other cell populations.
36 citations
TL;DR: Any boy or adult male with Addison's disease must be tested for X-linked ALD, because of the prognostic implications, the need for genetic counseling, and the potential benefit of therapeutic interventions.
Abstract: X-linked adrenoleukodystrophy (ALD) is a peroxisomal genetic disorder that causes adrenal insufficiency, demyelination in the central nervous system, and increased levels of very long chain fatty acids in tissues and body fluids. Although most cases appear in childhood as a devastating degenerative disorder or in adulthood as a milder disorder affecting the spinal cord, many patients have adrenal insufficiency prior to the onset of their neurologic deterioration for many years. Addison's disease without neurologic involvement may also remain the only clinical manifestation of X-linked ALD. Because of the prognostic implications, the need for genetic counseling, and the potential benefit of therapeutic interventions, any boy or adult male with Addison's disease must be tested for X-linked ALD.
TL;DR: Understanding of the normal processes by which peak adult bone mass is acquired and maintained, the physical, nutritional, and hormonal factors that regulate bone mass throughout adult life, and the critical role of reproductive hormonal replacement within the early years after menopause are improved.
Abstract: Recent years have seen considerable progress in our understanding of the normal processes by which peak adult bone mass is acquired and maintained, the physical, nutritional, and hormonal factors that regulate bone mass throughout adult life, and the critical role of reproductive hormonal replacement for maintaining bone mass within the early years after menopause. It is now apparent that loss of bone quantity is not sufficient to explain increased fracture risk. Bone fragility depends not only on its material properties, of which mineral content is an important component, but also on its microarchitecture and geometry. Age-related trabecular bone loss is manifest not simply as a global loss of bone, but is characterized by a loss of trabecular connectivity and increased cortical porosity. Appreciation of these issues along with understanding the lifelong process of bone remodeling are central to formulating rational strategies for preventing and treating osteoporosis.
TL;DR: Evidence is presented that the high percentage of body fat in mature women is necessary for regular ovulatory cycles and may influence reproductive ability directly, by influencing the direction of estrogen metabolism to more potent or less potent forms, or by changes in the binding properties of sex-hormone-binding globulin.
Abstract: Women with moderate weight loss (10%–15% of ideal weight) have secondary or primary amenorrhea. Athletic women also may have amenorrhea, or anovulatory cycles, though body weight may be in the normal range, since muscles are heavy (80% water compared with 5%–10% water in adipose tissue). The amenorrhea, which is usually reversible with weight gain, decreased exercise, or both, is due to hypothalamic dysfunction; the pituitary-ovary axis is intact, suggesting that this type of amenorrhea is adaptive, preventing an unsuccessful pregnancy. Evidence is presented that the high percentage of body fat (26%–28%) in mature women is necessary for regular ovulatory cycles and may influence reproductive ability directly: (a) as an extragonadal source of estrogen by aromatization of androgen to estrogen, (b) by influencing the direction of estrogen metabolism to more potent or less potent forms, or (c) by changes in the binding properties of sex-hormone-binding globulin. Indirect signals may be abnormal control of temperature and changes in energy metabolism that accompany excessive leanness.
TL;DR: A body of evidence suggests the involvement of protein kinases C and A in intermediary steps of gonadotropin synthesis and release.
Abstract: Genes encoding pituitary gonadotropins, luteinizing hormone, and follicle-stimulating hormone, as well as their transcripts, have been isolated from different species and characterized. The position of introns in the genes is highly conserved in different species, and it appears that sequences encoding gonadotropin subunits evolved from an ancestral gene. Expression of gonadotropin genes is regulated mainly by gonadotropin-releasing hormone (GnRH) and by gonadal steroids (estradiol and testosterone). Other factors, notably thyroid hormones and gonadal peptides (follistatin, inhibin, and activin), also play a role in this regulation. Although the intracellular mechanisms of GnRH signal transduction are still unclear, now a body of evidence suggests the involvement of protein kinases C and A in intermediary steps of gonadotropin synthesis and release.
TL;DR: Starting treatment by age three months has been shown to prevent severe intellectual deficit; thus mass screening can be considered cost-effective as compared with outlays for special care, education, and institutionalization.
Abstract: Population screening for congenital hypothyroidism was introduced in the early 1970s and now is routine in most of the industrialized world. Such screening has facilitated the characterization and refined the nosology of a spectrum of thyroid disorders in the neonatal period. Moreover, newborn screening has fulfilled the promise of minimizing the mental retardation otherwise common in infants with congenital hypothyroidism. Careful management of detected infants is essential, and physicians must remember that some infants, perhaps 10% of the total, may escape detection in screening programs. A high index of suspicion is necessary to assure early clinical detection and treatment of these infants.
TL;DR: In this paper, the thyroid-stimulating hormone (TSH) receptor was cloned by a strategy exploiting its belonging to the superfamily of G-protein-coupled receptors, and the recombinant human TSH receptor stably expressed in cell lines provides the tool to identify the targets of autoimmune reactions leading to Graves' disease and idiopathic myxedema.
Abstract: Thyroid-stimulating hormone (TSH) receptor has been cloned by a strategy exploiting its belonging to the superfamily of G-protein-coupled receptors. Comparison with the luteinizing hormone and follicle-stimulating hormone receptors shows that the glycoprotein hormone receptors constitute a subfamily of G-protein-coupled receptors with a large extracellular domain probably responsible for hormone binding. The recombinant human TSH receptor stably expressed in cell lines provides the tool to identify the targets of autoimmune reactions leading to Graves' disease and idiopathic myxedema.
TL;DR: The gene for generalized thyroid hormone resistance has been mapped to the c- erb Aβ thyroid hormone receptor on chromosome 3 in multiple kindreds and different mutations have been identified in the triiodothyronine (T 3 )-binding domain of c- erase Aβ and result in variable changes in T 3 binding affinity.
Abstract: The gene for generalized thyroid hormone resistance has been mapped to the c- erb Aβ thyroid hormone receptor on chromosome 3 in multiple kindreds. Different mutations have been identified in the triiodothyronine (T 3 )-binding domain of c- erb Aβ and result in variable changes in T 3 binding affinity. The variant phenotypes of thyroid hormone resistance are likely due to different mutations in the c- erb Aβ receptor.
TL;DR: Stringent dietary restrictions such as fasting may produce GH resistance by reducing the number of GH receptors, and less severe nutritional deprivation such a short-term protein restriction may cause GH insensitivity mainly through postreceptor mechanisms.
Abstract: Malnutrition results in poor growth and is associated with resistance to growth hormone (GH) action The mechanisms involved in the GH resistance depend on the severity and the timing of the nutritional insult Stringent dietary restrictions such as fasting may produce GH resistance by reducing the number of GH receptors Less severe nutritional deprivation such a short-term protein restriction may cause GH insensitivity mainly through postreceptor mechanisms
TL;DR: Although GH receptor expression is widespread, the cellular mechanisms by which GH binding to those receptors initiates cellular responses are still unclear, and functional expression of the cloned receptor in tissue culture has resulted in substantial progress toward that goal.
Abstract: Growth hormone (GH), synthesized in and secreted from the anterior pituitary lobe, has multiple effects at both the cellular and the organismal levels, including promotion of body growth, stimulation of intermediary metabolism, and transcriptional regulation of specific genes These effects are believed to be mediated by high-affinity cell-surface receptors, which have recently been cloned and characterized and found to be members of a newly described receptor family Although GH receptor expression is widespread, the cellular mechanisms by which GH binding to those receptors initiates cellular responses are still unclear Functional expression of the cloned receptor in tissue culture has resulted in substantial progress toward that goal
TL;DR: There is evidence that angiotensin II, in addition to being generated in the circulating blood, is synthesized in the anterior pituitary lobe and other endocrine tissues.
Abstract: There is evidence that angiotensin II, in addition to being generated in the circulating blood, is synthesized in the anterior pituitary lobe and other endocrine tissues. Angiotensin II produced locally may act on pituitary cell receptors to modulate or mediate the action of other hormonal factors. However, tissue angiotensins may be synthesized by a different mechanism than most other neuroendocrine peptides. A precise understanding of the mode of formation of local angiotensin II is necessary for the comprehension of its physiologic role in the pituitary gland.
TL;DR: Clinical assays for estrogen and progesterone receptors improve the selection of patients who may benefit from hormonal therapy and help to distinguish among patients with primary breast cancer who are at risk for early recurrence.
Abstract: The study of steroid hormone receptors in human breast cancer provides insight into tumor biology and forms the rationale for many therapeutic modalities. Clinical assays for estrogen and progesterone receptors improve the selection of patients who may benefit from hormonal therapy. In addition, receptor content in breast cancer tissue is useful for determining prognosis. Together with other new prognostic factors, hormone receptors help to distinguish among patients with primary breast cancer who are at risk for early recurrence.
TL;DR: In the normal thyroid, but not necessarily in the goitrous gland, the bulk of iodine is bound to thyroglobulin, and any change of thyroid function profoundly affects intrathyroidal iodine kinetics and produces a redistribution of stored iodine.
Abstract: In the normal thyroid, but not necessarily in the goitrous gland, the bulk of iodine is bound to thyroglobulin. Even in the normal thyroid—and much more so in goiters—iodine is contained in many different compartments with widely differing kinetics, biochemical composition, localization, and physiologic significance. Any change of thyroid function profoundly affects intrathyroidal iodine kinetics and produces a redistribution of stored iodine. This must be taken into account whenever the impact of a global change in intrathyroidal iodine stores on thyroid function and growth is studied in vivo.
TL;DR: Analysis of patients with Laron-type dwarfism should provide insight into the mechanisms of hormone receptor binding and signal transduction pathways of this receptor, which belongs to a new class of transmembrane receptors.
Abstract: An autosomal recessive disorder, Laron-type dwarfism, results from peripheral unresponsiveness to growth hormone. Mutations in the growth hormone receptor have recently been identified in this syndrome. Analysis of patients with Laron-type dwarfism should provide insight into the mechanisms of hormone receptor binding and signal transduction pathways of this receptor, which belongs to a new class of transmembrane receptors.
TL;DR: Based on retrograde tracing studies in combination with immunocytochemistry, the origin of many nerve terminals in the median eminence has been determined and may function as neurohormones acting an the pituitary or neurotransmitters affecting the activity of other neurons in the central nervous system.
Abstract: Nearly 40 putative neurotransmitters and other chemical messengers, mostly peptides, are present in the median eminence that constitutes the final common pathway for signals from the brain to the pituitary. The majority of them are produced in perikarya located in different nuclei of the hypothalamus; however, some of them arise from the brainstem. The neurons contacting capillaries of the median eminence (hypophysiotropic neurons) are intermixed with neurons containing the same transmitter (hypophysiotropic factor 1 ), but projecting to other areas of the brain. Depending on their site of release, the hypophysiotropic factors may function as neurohormones acting an the pituitary or neurotransmitters affecting the activity of other neurons in the central nervous system. Based on retrograde tracing studies in combination with immunocytochemistry, the origin of many nerve terminals in the median eminence has been determined.
TL;DR: The results support the overall hypotheses that the quality as well as the quantity of FSH are significant contributors to target cell signal transduction and that distinct FSH isoforms with different functional capabilities influence the expression of acute (ovulation) and chronic reproductive events.
Abstract: Specific and sensitive in vitro bioassays suitable for measurement of follicle-stimulating hormone (FSH) in small quantities of serum and urine have recently been validated. Comparisons of bioassay (B-FSH) potencies with immunoassay (I-FSH) estimates and chromatofocusing patterns have facilitated new discoveries regarding the regulation of FSH biosynthesis, storage, secretion, serum concentrations and target cell responsiveness, plasma clearance, and the significance of excreted forms. A review of recent studies reveals that luteinizing hormone and FSH, as well as B-FSH and I-FSH, appear to be differentially regulated by GnRH, GnRH agonists and antagonists, sex steroids and gonadal peptides in both sexes, with significant differences between the sexes. The results support the overall hypotheses that the quality as well as the quantity of FSH are significant contributors to target cell signal transduction and that distinct FSH isoforms with different functional capabilities influence the expression of acute (ovulation) and chronic reproductive events.
TL;DR: Although more extensive investigation is required, delineation of an immune axis involving prolactin, VIP, and somatostatin in mucosal immune tissue such as mammary gland is a promising area of research with clinical relevance to neonatal resistance to infection.
Abstract: Prolactin, estrogen, and progesterone together induce proliferation of the mammary glands with a coincident increase in the IgA-secreting plasma cells in the tissue. Of these three hormones, Prolactin is the most effective single peptide in stimulating IgA production. Vasoactive intestinal peptide (VIP) and somatostatin have also been shown to modulate IgA production. Although more extensive investigation is required, delineation of an immune axis involving prolactin, VIP, and somatostatin in mucosal immune tissue such as mammary gland is a promising area of research with clinical relevance to neonatal resistance to infection.
TL;DR: Evidence from a variety of experimental systems indicates that insulin plays a role in neuronal growth and differentiation; additional functions may exist in the adult brain.
Abstract: Insulin and insulin receptors are present in brain and appear to function outside the realm of glucose homeostasis. Insulin receptors in the brain are structurally unique and appear to be found exclusively on neurons. Evidence from a variety of experimental systems indicates that insulin plays a role in neuronal growth and differentiation; additional functions may exist in the adult brain. Insulin action in neurons may be associated with unique signal transduction pathways.
TL;DR: Islet amyloid polypeptide (IAPP or amylin) as mentioned in this paper is a peptide produced in the pancreatic beta-cell secretory granule that is costored and coreleased with insulin.
Abstract: Islet amyloid polypeptide (IAPP or amylin), first identified as the peptide deposited as amyloid in type-2 diabetic pancreas and insulinoma, turns out to be a peptide produced in the pancreatic beta-cell secretory granule that is costored and coreleased with insulin. Experimental evidence suggests that, under certain conditions, IAPP can counter insulin action in peripheral tissue and inhibit insulin release from the pancreas. IAPP therefore appears to respond to the same physiologic stimuli as insulin, but has opposing biologic actions. The role of IAPP, both in normal physiology and in pathology, remains unclear, but current evidence suggests against a role as a circulating hormone in favor of a paracrine or autocrine modulator of insulin secretion.
TL;DR: Bone mass measurements, when considered in the context of age, life expectancy, expected bone loss, and other risk factors, enable improved patient risk stratification, and more rational treatment choices.
Abstract: Initiation of estrogens or other drugs as preventive measures for osteoporosis should be based upon objective estimates of actual, future fracture risk. Bone mass measurements, when considered in the context of age, life expectancy, expected bone loss, and other risk factors, enable improved patient risk stratification, and more rational treatment choices.
TL;DR: In suckling mammals, hormones and neuropeptides are absorbed through the gastrointestinal tract and appear intact in the plasma, which is age dependent and could have physiologic significance in neonatal development.
Abstract: Milk, which is a mammal-specific biologic fluid, contains several neuroendocrine peptides at concentrations higher than those found in plasma. These neuroendocrine peptides can be synthesized or processed in the mammary gland or excreted into milk through various pathways. In addition, certain milk proteins, notably casein, can be enzymatically processed to release "exorphins," peptides with opioid activities. In suckling mammals, hormones and neuropeptides are absorbed through the gastrointestinal tract and appear intact in the plasma. This absorption is age dependent and could have physiologic significance in neonatal development.