Showing papers in "Endocrine Reviews in 1982"
TL;DR: Assessment of thyroid function in patients with systemic nonthyroidal illness, as well as in those undergoing a variety of other stresses, is complicated by effects at all levels of the hypothalamic-pituitary-thyroid axis.
Abstract: GENERALLY, the purpose of assessing thyroid function in a given patient is to determine his metabolic status. In patients with systemic nonthyroidal illness, as well as in those undergoing a variety of other stresses, this determination is complicated by effects at all levels of the hypothalamic-pituitary-thyroid axis. With the availability of thyrptropin releasing hormone (TRH) and the recent development of sensitive methods for the direct measurement of serum 3,5,3′-triiodothyronine (T3) and 3,3′,5′-triiodothyronine (reverse T3 (rT3)), considerable progress has been made in gaining an understanding of the significance of the alterations in thyroid hormone economy that accompany nonthyroidal illness, stress, and the administration of certain pharmacological agents. According to basic tenets of negative feedback control of thyrotropin (TSH) secretion by circulating free thyroid hormones, alterations in hormone binding in nonthyroidal illness that produce increases in free hormone should result in predicta...
885 citations
TL;DR: Vitamin D was first identified through the nutritional studies of Sir Edward Mellanby (243), which identified rickets as a disease state resulting from a deficiency of vitamin D, as well as through the biochemical/chemical studies of McCollum and co-workers (242), who demonstrated that there was more than one fat-soluble vitamin.
Abstract: Introduction Vitamin D is generally accepted as being essential for life in higher animals (278). It is one of the most important biological regulators of calcium and phosphorus (406) metabolism. Along with the two peptide hormones PTH and calcitonin, vitamin D is responsible for the minute-to-minute as well as the day-to-day establishment and maintenance of calcium homeostasis. The substance vitamin D, or cholecalciferol, was first identified through the nutritional studies of Sir Edward Mellanby (243), which identified rickets as a disease state resulting from a deficiency of vitamin D, as well as through the biochemical/chemical studies of McCollum and co-workers (242), who demonstrated that there was more than one fat-soluble vitamin. Together these studies established a deficiency state, namely rickets, which was attributable to the newly discovered, nutritionally important fat-soluble component, vitamin D. In retrospect, however, the most important discovery related to the appreciation by Huldschins...
625 citations
TL;DR: The development of male germ cells in the seminiferous tubules of the testis involves three main phases: spermatogonial multiplication, meiosis, and spermiogenesis, which follows each other in regular fashion, giving rise to the wave of the seminifierous epithelium in most mammals.
Abstract: The development of male germ cells in the seminiferous tubules of the testis involves three main phases: spermatogonial multiplication, meiosis, and spermiogenesis. In the seminiferous epithelium, cells in these developmental phases are arranged in defined associations or stages. Along the seminiferous tubules, these stages follow each other in regular fashion, giving rise to the wave of the seminiferous epithelium in most mammals. The time interval between the appearance of the same cell association at a given point of the tubule is called the cycle of the seminiferous epithelium. The dependence of spermatogenesis on pituitary FSH and on androgens secreted by Leydig cells in the testicular interstitial tissue is well documented. The somatic components of the seminiferous epithelium, the Sertoli cells, are the primary targets of these hormones. However, the local mechanisms, i.e. how Sertoli cells interact with the germ cells at various stages of the seminiferous epithelial cycle, have remained poorly und...
608 citations
TL;DR: Two distinct lipoprotein-specific, hormonally regulated mechanisms for Lipoprotein cholesterol uptake by steroidogenic tissues have been elucidated.
Abstract: I. Introduction Cholesterol is an obligate intermediate in steroidogenesis. It may be synthesized by steroidogenic cells or taken up from circulating lipoproteins. In the adrenal, ovary, placenta, and possibly the testes of many species, including man, lipoprotein cholesterol is the major source of steroidogenic substrate. Lipoprotein cholesterol uptake is hormonally regulated in these tissues, with the exception of the placenta, and coordinated with intracellular cholesterol synthesis and mobilization of cholesteryl esters to ensure a continuous supply of free cholesterol for steroid synthesis. When the rate of cholesterol uptake exceeds the rate of steroidogenesis, intracellular cholesterol synthesis is suppressed and cholesterol in excess of cellular needs is esterified and stored for future use. During the last decade the mechanisms and regulation of lipoprotein cholesterol uptake by steroidogenic tissues have been elucidated. Two distinct lipoprotein-specific, hormonally regulated mechanisms for taki...
574 citations
TL;DR: Since saliva samples can be collected at frequent intervals by both adults and children, they facilitate short term dynamic tests, pharmacokinetic analyses, and studies of chronobiological changes and measurement of steroids in saliva is attractive.
Abstract: SOME difficulties in clinical studies of endocrine function based on plasma sampling regimens include time-consuming venipuncture and measurement of the “total” rather than the “free” biologically active fraction in plasma. Simple methods for determining plasma free steroids have not yet been developed, and most current procedures involve technically demanding ultrafiltration or equilibrium dialysis. In this context measurement of steroids in saliva is attractive. Steroid concentrations in saliva are independent of flow rate and reflect those in the free fraction in plasma. Recent improvements in immunoassay techniques have allowed development of simple, high output assays for salivary steroids which are well suited for routine use. Since saliva samples can be collected at frequent intervals by both adults and children, they facilitate short term dynamic tests, pharmacokinetic analyses, and studies of chronobiological changes. Problems of viscosity, which restrict processing of freshly collected saliva, m...
437 citations
TL;DR: This work has followed an arduous and often tortuous route to reach the current understanding of the physiological role of catecholamines (CAs) in the regulation of gonadotropin secretion.
Abstract: I. Introduction We have followed an arduous and often tortuous route to reach our current understanding of the physiological role of catecholamines (CAs) in the regulation of gonadotropin secretion. More often than not, the vast amounts of confusing literature on this subject have bewildered the novice and discouraged the faint of heart and, as such, research into the complexities of this system have waxed and waned over the 32 or more years since CAs first were implicated as regulators of gonadotropin secretion. Much of this confusion was due to: 1) lack of adequate methodology to measure CA secretion; 2) the use of complex and at times unusual experimental animal preparations and paradigms; 3) an inadequate understanding of the neuroanatomy of CA pathways in the brain; and 4) the use of many drugs which lack the specificity required to delineate the interplay that exists between CAs and the secretion of gonadotropic hormones. This is not to say that we now have deciphered the many complex central nervou...
369 citations
TL;DR: The purpose of this review is to compare the findings on various steroid receptors and to suggest that there may be certain broad similarities about these receptors.
Abstract: I. Introduction Steroid hormones act on a wide variety of target cells to alter their structure and function in remarkably diverse ways. However, much evidence has accumulated to suggest that the different steroid hormones, and even the sterol 1,25-dihydroxyvitamin D, act via similar pathways to produce the same general effects, i.e. the induction of RNA and protein synthesis. These effects are mediated by specific, high affinity hormone-binding proteins termed “receptors.” Steroid receptors have been described in many different target tissues, and they often seem to display as many differences as similarities in both their native structure and their various in vitro physicochemical transformations. Yet the homologies of structure of the different steroid hormones, and the similarities in their effector pathways and general metabolic effects, suggest that there may be certain broad similarities about these receptors. It is the purpose of this review to compare the findings on various steroid receptors and...
314 citations
TL;DR: It is shown that stress-induced activation of the central nervous system is transduced from a neural into a humoral signal in the hypothalamus, and chemical transmitter substances elaborated are transported to the adenohypophysis via the hypophyseal portal circulation to stimulate the secretion of ACTH from the corticotrophs.
Abstract: IN 1948 Geoffrey Harris (1) hypothesized that stress-induced activation of the central nervous system is transduced from a neural into a humoral signal in the hypothalamus. Resultant chemical transmitter substances elaborated are transported to the adenohypophysis via the hypophyseal portal circulation to stimulate the secretion of ACTH from the corticotrophs. Despite intensive studies by many investigators throughout the world in the intervening years, identification of this putative neurotransmitter has been extremely difficult. Slusher and Roberts (2) were the first to describe ACTH-releasing activity in a hypothalamic extract. Unfortunately, the assay using intact, untreated rats employed in their experiments was inadequately refined (2, 3) since such animals will secrete ACTH in response to a variety of nonspecific stresses. In 1955 more specific experimental evidence for the existence of a brain extract that stimulated ACTH secretion was independently presented by Saffran and Serially (4) and Guille...
312 citations
TL;DR: A large group of in vivo and in vitro studies indicate that, in adult male mammals, the anterior pituitary and several central nervous structures (in descending order: the hypothalamus, the midbrain, the amygdala,...
Abstract: Introduction It is now well established that the prostate and other androgen-sensitive peripheral structures (seminal vesicles, sebaceous gland, kidney, etc.) metabolize testosterone into 5α-androstane-17β-ol-3-one (dihydrotestosterone, DHT) and subsequently into 5α-androstane-3α, 17β diol (3α-diol) (1–6). In the peripheral androgen-responding tissues little amounts of 5α-androstane-3β,17β-diol (3β-diol) are also formed from DHT (7–9). These conversions occur under the influence of an enzymatic complex that includes a 5α-reductase, and two (3α- and 3β-) hydroxysteroid dehydrogenases. According to a theory which is now generally accepted, these 5α-reduced metabolites act as the intracellular mediators for many of the multiple actions testosterone exerts on its target structures (1–3, 10). A large group of in vivo and in vitro studies indicate that, in adult male mammals, the anterior pituitary (11–25) and several central nervous structures (in descending order: the hypothalamus, the midbrain, the amygdala,...
246 citations
TL;DR: It is suggested that malignant parathyroid disease usually presented somewhat differently than the much more common benign form of primary hyperparathyroidism, which has documented a rather dramatic change in its incidence and clinical presentati...
Abstract: CARCINOMA of the parathyroid gland is a rare cause of primary hyperparathyroidism, accounting for approximately 3–4% of patients with hypercalcemia and elevated parathyroid hormone levels (1, 2). In 1969, Holmes et al. (3) reviewed the data on 46 patients with parathyroid carcinoma published since the original description of the disease in 1938. The subjects of that report had, in general, marked and symptomatic hypercalcemia as well as the frequent presence of both skeletal and renal complications of hyperparathyroidism. These observations suggested that malignant parathyroid disease usually presented somewhat differently than the much more common benign form of primary hyperparathyroidism. Since the report of Holmes et al. (3) there have been additional clinical descriptions of parathyroid carcinoma but no further comprehensive reviews in English. Over this same period of time, surveys of benign primary hyperparathyroidism have documented a rather dramatic change in its incidence and clinical presentati...
222 citations
TL;DR: The present review is devoted to those aspects of simple goiter which have not been explained by the investigations on iodine deficiency, including structural and functional heterogeneity between single follicles or between different regions of a goiter.
Abstract: IN THE past two decades, research on simple goiter has concentrated on the mechanisms which govern the adaptation of the thyroid gland to iodine deficiency. As a result of these investigations, the pathogenesis of goiters induced by shortage of iodine is rather well understood at the present time. The accumulated knowledge has been laid down in a number of easily accessible reviews (1–57). In contrast to previously published work, the present review is devoted to those aspects of simple goiter which have not been explained by the investigations on iodine deficiency. They include structural and functional heterogeneity between single follicles or between different regions of a goiter, the growth of goiters in spite of abundant iodine supply, the development of single and multiple nodules, the pathogenesis of cold and hot follicles, and the pathogenesis of hyperthyroidism in simple goiter. A. Definition of Simple Goiter Simple goiter is a slowly developing diffuse or nodular enlargement of the thyroid gland...
TL;DR: The present status of relaxin is such that it directly impinges on reproductive endocrinology and perhaps on those endocrinologists who appreciate that connective tissue metabolism is controlled by hormones and who wish to share in the task of refurbishing a hormone long left on the shelf.
Abstract: RELAXIN was described as a hormone some 55 years ago but despite some persistent pioneering work, passed into relative obscurity for a long period of time. The present status of relaxin is such that it directly impinges on reproductive endocrinology and perhaps on those endocrinologists who appreciate that connective tissue metabolism is controlled by hormones and who wish to share in the task of refurbishing a hormone long left on the shelf. There is no question but that work on relaxin was at a low ebb for 40 years after its initial discovery by Frederick Hisaw in 1926. Certainly part of the resurgence of work on relaxin in the early 1970s is identified with initiatives of Dr. Steinetz, and there is now a sufficient body of knowledge to warrant its integration into general endocrinology. A documentation of the reasons for the neglect of relaxin would make an interesting exercise in the history of endocrinology but is outside the scope of this review. I mention my perceptions below because they may becom...
TL;DR: For a long time the function of this organ remained unidentified, and tetany after thyroid surgery was considered the result of the absence of the thyroid, while it was discovered that the parathyroid glands were closely linked to tetany did they begin to receive attention.
Abstract: ONE HUNDRED years ago, the Swedish medical student Ivan Sandstrom (1) discovered the parathyroid glands in dogs and described their existence in man, horses, oxen, rabbits, and cats. He never realized the significance of his discovery or the important function of this organ in the control of calcium metabolism. For a long time the function of this organ remained unidentified, and tetany after thyroid surgery was considered the result of the absence of the thyroid. Not until it was discovered that the parathyroid glands were closely linked to tetany did they begin to receive attention. Gley (2) observed that 14 of 16 rabbits died of tetany if, together with the thyroid gland, two other glands lying underneath it were removed. Subsequent attempts to repeat these experiments failed because nothing was known about the internal and external arrangements of these glands. Not until Kohn (3) described these internal glands as existing in a great variety of animals did the basis exist for the experiments of two It...
TL;DR: Receptor-mediated endocytosis, a device for both selecting and concentrating specific solutes for internalization by virtue of their binding to cell surface receptors, has now been described for a first time.
Abstract: ENDOCYTOSIS refers to the uptake of materials into cells from the external environment by means of vesicles derived from invaginations of the cell surface. Several types of endocytosis have been distinguished (1). Phagocytosis (cell eating) describes the uptake of large particulate matter; whereas pinocytosis (cell drinking) refers to the internalization of fluid and small particles. Although the term endocytosis in its general sense subsumes phagocytototic behavior, it has frequently been used interchangeably with pinocytosis, a universal activity of living cells. The terms adsorptive and fluid phase endocytosis (pinocytosis) distinguish between the uptake of macromolecules bound to the cell surface (and eventually the inner membrane of vesicles) and the uptake of solute in the extracellular fluid. The former is a device for both selecting and concentrating specific solutes for internalization by virtue of their binding to cell surface receptors. Receptor-mediated endocytosis has now been described for a...
TL;DR: It has been demonstrated that most, if not all, estrogen formed in children, men, and anovulatory and postmenopausal women arises by the extraglandular aromatization of plasma C19-steroids.
Abstract: EXTRAGLANDULAR steroid hormone formation is now established as a physiological as well as a pathophysiological phenomenon in men, women, and children (1–8). Indeed, it has been demonstrated that most, if not all, estrogen formed in children (9, 10), men (1, 6, 11, 12), and anovulatory (13–15) and postmenopausal (1, 12, 13, 16–21) women arises by the extraglandular aromatization of plasma C19-steroids. Greater than normal extraglandular estrogen formation can give rise to feminization in men (1, 3–6, 8, 9, 22–25) and to uterine bleeding (1, 13–15, 17, 19, 21, 26, 27) and possibly to endometrial carcinoma in women (17, 19, 21, 26). It also is known that the biologically potent androgen testosterone can be produced in extraglandular tissues from circulating precursors (28–33). In fact, most of the testosterone produced in young women arises by this mechanism (28, 29, 31, 32). In addition to the extraglandular formation of biologically active steroid hormones, it now is known that potent steroid hormones are ...
TL;DR: The approach to these problems is illustrated by seven cases, and it is emphasized that the proper management of CS requires both correct diagnosis and the logical application of all available therapies.
Abstract: CS comprises a group of disorders characterized by hypercortisolism. The variety of causes--pituitary-dependent CS (CD), adrenal tumor, and the ectopic ACTH syndrome--necessitates a variety of therapies--surgical, radiotherapeutic, and medical. Once a specific diagnosis is made, specific therapy can be instituted. Although some controversy persists regarding treatment, particularly that of CD, for most patients it is straightforward. However, in our experience with more than 60 patients, therapeutic dilemmas can arise in a number of circumstances, e.g. the patient with the radiologically normal sella or recurrent CD after adrenalectomy. In addition, the treatment of such conditions as the large ACTH-producing pituitary tumor, Nelson's syndrome, the malignant ectopic ACTH syndrome, and adrenal carcinoma is not entirely satisfactory. Our approach to these problems is illustrated by seven cases, and we emphasize that the proper management of CS requires both correct diagnosis and the logical application of all available therapies.
TL;DR: This review will outline the general methodology and recent developments in the production of monoclonal antibodies and then focus on the many successful applications of these techniques to endocrine research.
Abstract: “IMMUNOLOGICAL” techniques (at times pioneered by “endocrinologists”) such as RIAs, immunoradiometric assays, immunocytochemistry, and affinity chromatography are central to current endocrine research. Development of a methodology that would allow the production of unlimited quantities of homogeneous antibody reagents would therefore have a major impact on the field of endocrinology. In addition to the provision of large quantities of homogeneous antibody, monoclonal antibody techniques allow investigators to produce antibodies reacting with single antigenic determinants, despite immunization with impure antigens. The production of monoclonal antibodies to cell surface differentiation antigens after immunization with whole cells is a striking example of immunization with “impure” antigens. In this review we will outline the general methodology and recent developments in the production of monoclonal antibodies and then focus on the many successful applications of these techniques to endocrine research. I. ...