Differential Biological Activity of Estradiol Metabolites

PEDIATRICS ◽  
1978 ◽  
Vol 62 (6) ◽  
pp. 1128-1133
Author(s):  
Jack Fishman ◽  
Charles Martucci
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Biological Activity ◽  
Estrogenic Activity ◽  
Critical Role ◽  
Pituitary Hormone ◽  
Clear Cut ◽  
The Central Nervous System ◽  
Estradiol Metabolites ◽  
The One

Assessment of the biological potency of an estrogen in the human has been and remains a formidable task. The problem arises not only from the lack of a readily distinguished physiological endpoint, but also from the diversity of the biological actions of the estrogens. Estrogens exert proliferative effects in recognized target tissues such as endometrium, vagina, and breast,1 and this action is the one commonly associated with the term "estrogenicity." Estrogens, however, also participate in inducing a host of other peripheral responses in tissues such as blood, bone, skin, and others.2 More importantly, the estrogens also exercise major regulatory functions in the central nervous system, including control of pituitary hormone secretion3 and influencing behavior such as food intake4 and sexual receptivity.5 Much attention had been devoted to the design of estrogen structures that would exhibit a specific type of estrogenic activity, such as gonadotropic regulation, without retaining any uterotropic action. Despite the vast numbers of structures synthesized, little clear-cut separation of these activities has been achieved, suggesting that these dual actions of estrogens may be inextricably linked to each other. On the other hand, much effort has also gone into the study of the mechanism of estrogen action in the uterus and in the central nervous system; despite much progress in both directions, little evidence of a commonality between these two responses to estradiol has so far emerged, suggesting that they may not be directly linked. In our studies, we sought to examine whether estradiol metabolism may play a critical role in the expression of the biological activity of the female sex hormone.

Central Nerve System Impairment, AMA Guides, Sixth Edition: An Overview

2018 ◽  
Vol 23 (1) ◽  
pp. 10-13
Author(s):  
James B. Talmage ◽  
Jay Blaisdell
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Neurological Impairment ◽  
Sixth Edition ◽  
Central Nerve System ◽  
The Central Nervous System ◽  
The One ◽  
Nerve System ◽  
The Brain

Abstract Injuries that affect the central nervous system (CNS) can be catastrophic because they involve the brain or spinal cord, and determining the underlying clinical cause of impairment is essential in using the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), in part because the AMA Guides addresses neurological impairment in several chapters. Unlike the musculoskeletal chapters, Chapter 13, The Central and Peripheral Nervous System, does not use grades, grade modifiers, and a net adjustment formula; rather the chapter uses an approach that is similar to that in prior editions of the AMA Guides. The following steps can be used to perform a CNS rating: 1) evaluate all four major categories of cerebral impairment, and choose the one that is most severe; 2) rate the single most severe cerebral impairment of the four major categories; 3) rate all other impairments that are due to neurogenic problems; and 4) combine the rating of the single most severe category of cerebral impairment with the ratings of all other impairments. Because some neurological dysfunctions are rated elsewhere in the AMA Guides, Sixth Edition, the evaluator may consult Table 13-1 to verify the appropriate chapter to use.

Heterogeneity and Proliferative and Differential Regulators of NG2-glia in Physiological and Pathological States

2020 ◽  
Vol 27 (37) ◽  
pp. 6384-6406 ◽  
Author(s):  
Zuo Zhang ◽  
Hongli Zhou ◽  
Jiyin Zhou
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Physiological State ◽  
Critical Role ◽  
Adult Brain ◽  
Pathological State ◽  
Peripheral Neurons ◽  
Neuronal Synapses ◽  
The Central Nervous System ◽  
Rapid Modulation

NG2-glia, also called Oligodendrocyte Precursor Cells (OPCs), account for approximately 5%-10% of the cells in the developing and adult brain and constitute the fifth major cell population in the central nervous system. NG2-glia express receptors and ion channels involved in rapid modulation of neuronal activities and signaling with neuronal synapses, which have functional significance in both physiological and pathological states. NG2-glia participate in quick signaling with peripheral neurons via direct synaptic touches in the developing and mature central nervous system. These distinctive glia perform the unique function of proliferating and differentiating into oligodendrocytes in the early developing brain, which is critical for axon myelin formation. In response to injury, NG2-glia can proliferate, migrate to the lesions, and differentiate into oligodendrocytes to form new myelin sheaths, which wrap around damaged axons and result in functional recovery. The capacity of NG2-glia to regulate their behavior and dynamics in response to neuronal activity and disease indicate their critical role in myelin preservation and remodeling in the physiological state and in repair in the pathological state. In this review, we provide a detailed summary of the characteristics of NG2-glia, including their heterogeneity, the regulators of their proliferation, and the modulators of their differentiation into oligodendrocytes.

Central mineralocorticoid receptor blockade decreases plasma TNF-α after coronary artery ligation in rats

2003 ◽  
Vol 284 (2) ◽  
pp. R328-R335 ◽  
Author(s):  
Joseph Francis ◽  
Robert M. Weiss ◽  
Alan Kim Johnson ◽  
Robert B. Felder
Keyword(s):  
Heart Failure ◽  
Central Nervous System ◽  
Nervous System ◽  
Mineralocorticoid Receptor ◽  
Critical Role ◽  
Evaluation Study ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Tnf Α ◽  
The Central Nervous System

The Randomized Aldactone Evaluation Study (RALES) demonstrated a substantial clinical benefit to blocking the effects of aldosterone (Aldo) in patients with heart failure. We recently demonstrated that the enhanced renal conservation of sodium and water in rats with heart failure can be reduced by blocking the central nervous system effects of Aldo with the mineralocorticoid receptor (MR) antagonist spironolactone (SL). Preliminary data from our laboratory suggested that central MR might contribute to another peripheral mechanism in heart failure, the release of proinflammatory cytokines. In the present study, SL (100 ng/h for 21 days) or ethanol vehicle (Veh) was administered via the 3rd cerebral ventricle to one group of rats after coronary ligation (CL) or sham CL (Sham) to induce congestive heart failure (CHF). In Veh-treated CHF rats, tumor necrosis factor-α (TNF-α) levels increased during day 1 and continued to increase throughout the 3-wk observation period. In CHF rats treated with SL, started 24 h after CL, TNF-α levels rose initially but retuned to control levels by day 5 after CL and remained low throughout the study. These findings suggest that activation of MR in the central nervous system plays a critical role in regulating TNF-α release in heart failure rats. Thus some of the beneficial effect of blocking MR in heart failure could be due at least in part to a reduction in TNF-α production.

scholarly journals Identification of a Novel BRCA1 Alteration in Recurrent Melanocytoma Resulting in Increased Proliferation

2020 ◽  
Vol 79 (11) ◽  
pp. 1233-1238
Author(s):  
Teresa San-Miguel ◽  
Lara Navarro ◽  
Beatriz Sánchez-Sendra ◽  
Javier Megías ◽  
Lisandra Muñoz-Hidalgo ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Prognostic Value ◽  
Proliferation Index ◽  
Benign Neoplasms ◽  
Epigenetic Changes ◽  
Epigenetic Landscape ◽  
Meningeal Melanocytoma ◽  
The Central Nervous System ◽  
The One

Abstract Primary meningeal melanocytomas are rare tumors of the central nervous system. Although they are considered benign neoplasms, some reports describe recurrent rates up to 45%. Little is known about their genetic and epigenetic landscape because of their infrequency. Even less has been described about markers with prognostic value. Here we describe a patient who developed a primary meningeal melanocytoma, suffered 3 recurrences in a period of 6 years and died of the tumor. The genetic and epigenetic changes explored confirmed GNAQ mutation as an initiating event. We found an epigenetic alteration of GSTP1, a feature that has recently been described in meningiomas, from the beginning of the disease. In addition, there was loss of heterozygosity in BRCA1 beginning in the second recurrence that was linked to an increase in the proliferation index; this suggested a progression pathway similar to the one described in uveal melanomas. These findings underscore the necessity of further research focused on these tumors.

scholarly journals Snapin deficiency is associated with developmental defects of the central nervous system

2010 ◽  
Vol 31 (2) ◽  
pp. 151-158 ◽  
Author(s):  
Bing Zhou ◽  
Yi-Bing Zhu ◽  
Lin Lin ◽  
Qian Cai ◽  
Zu-Hang Sheng
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Protein Quality ◽  
Third Ventricle ◽  
Critical Role ◽  
Developmental Defects ◽  
Lysosomal Function ◽  
Quality Control Process ◽  
The Central Nervous System

The autophagy–lysosomal pathway is an intracellular degradation process essential for maintaining neuronal homoeostasis. Defects in this pathway have been directly linked to a growing number of neurodegenerative disorders. We recently revealed that Snapin plays a critical role in co-ordinating dynein-driven retrograde transport and late endosomal–lysosomal trafficking, thus maintaining efficient autophagy–lysosomal function. Deleting snapin in neurons impairs lysosomal proteolysis and reduces the clearance of autolysosomes. The role of the autophagy–lysosomal system in neuronal development is, however, largely uncharacterized. Here, we report that snapin deficiency leads to developmental defects in the central nervous system. Embryonic snapin−/− mouse brain showed reduced cortical plates and intermediate zone cell density, increased apoptotic death in the cortex and third ventricle, enhanced membrane-bound LC3-II staining associated with autophagic vacuoles and an accumulation of polyubiquitinated proteins in the cortex and hippocampus. Thus our results provide in vivo evidence for the essential role of late endocytic transport and autophagy–lysosomal function in maintaining neuronal survival and development of the mammalian central nervous system. In addition, our study supports the existence of a functional interplay between the autophagy–lysosome and ubiquitin–proteasome systems in the protein quality-control process.

scholarly journals Expression of c-kit and kit ligand proteins in normal human tissues.

1994 ◽  
Vol 42 (11) ◽  
pp. 1417-1425 ◽  
Author(s):  
A Lammie ◽  
M Drobnjak ◽  
W Gerald ◽  
A Saad ◽  
R Cote ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Critical Role ◽  
Regional Distribution ◽  
Cervix Uterus ◽  
Sweat Glands ◽  
Human Tissues ◽  
Mouse Development ◽  
Normal Tissues ◽  
The Central Nervous System

The c-kit receptor and its cognate ligand, KL, play a critical role in melanogenesis, gametogenesis, and hematopoiesis. Studies on the expression of c-kit and KL have been primarily focused on mouse development. We undertook the present study to characterize the pattern of expression of these molecules in normal adult human tissues. Using immunohistochemistry and consecutive tissue sections from the same block, we evaluated a variety of well-preserved normal tissues for c-kit and KL microanatomic distribution. c-kit protein was identified in tissue mast cells, melanocytes, glandular epithelial cells of breast, parotid, dermal sweat, and esophageal glands. Scattered c-kit immunoreactivity was also observed for testicular and ovarian interstitial cells. A striking regional distribution of c-kit was detected in the central nervous system, particularly in the cerebellum, hippocampus, and dorsal horn of the spinal cord. KL protein was identified in cells complementary to staining for the receptor, such as glandular myoepithelium of breast and sweat glands. Intense KL immunoreactivity was observed in smooth muscle cells of the bladder, cervix, uterus, and gastrointestinal tract, as well as in striated and cardiac muscle. Strong KL staining was also detected in prostate fibromuscular stroma cells. In the central nervous system, KL expression was confined to Golgi and Purkinje cells in the cerebellum. These results suggest a role for this receptor and its ligand in the maintenance of a variety of fully differentiated tissues.

scholarly journals Death of developing neurons: New insights and implications for connectivity

2013 ◽  
Vol 203 (3) ◽  
pp. 385-393 ◽  
Author(s):  
Martijn P.J. Dekkers ◽  
Vassiliki Nikoletopoulou ◽  
Yves-Alain Barde
Keyword(s):  
Central Nervous System ◽  
Cell Death ◽  
Nervous System ◽  
Growth Factors ◽  
Axonal Degeneration ◽  
Neuronal Development ◽  
Critical Role ◽  
Synaptic Function ◽  
The Central Nervous System ◽  
Developing Neurons

The concept that target tissues determine the survival of neurons has inspired much of the thinking on neuronal development in vertebrates, not least because it is supported by decades of research on nerve growth factor (NGF) in the peripheral nervous system (PNS). Recent discoveries now help to understand why only some developing neurons selectively depend on NGF. They also indicate that the survival of most neurons in the central nervous system (CNS) is not simply regulated by single growth factors like in the PNS. Additionally, components of the cell death machinery have begun to be recognized as regulators of selective axonal degeneration and synaptic function, thus playing a critical role in wiring up the nervous system.

Infestations expérimentales de crabes juvéniles par la sacculine. Ultrastructure des racines parasitaires en croissance et relations avec la niasse ganglionnaire ventrale de l'hôte

1981 ◽  
Vol 59 (9) ◽  
pp. 1818-1826 ◽  
Author(s):  
Geneviève G. Payen ◽  
Michelle Hubert ◽  
Yves Turquier ◽  
Claudio Rubiliani ◽  
Colette Chassard-Bouchaud
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Connective Tissue ◽  
Host Defense ◽  
Root Cells ◽  
Sacculina Carcini ◽  
The Central Nervous System ◽  
The One ◽  
Host Tissues

Experimental infestations of young Carcinus with Sacculina carcini indicate that the ventral ganglionic mass (VGM) is the first "target" of the parasite roots into the host tissues. As in pubescent crabs naturally parasitized, either with or without an external visceral sac, the roots penetrate and invade that area of the central nervous system during the first month of infestation.Ultrastructural study of the developing roots, in contact with the VGM, leads to the conclusion that apart from a few embryonic characters, the root cells show a cytostructure similar to the one that has been observed in the roots naturally parasitizing pubescent crabs, whether the external visceral sac is present or not.In the two cases of infestation the roots which cross the neurolemma bring about a marked disorganization of ganglia in consequence of the alteration of the neuroglia, neuropiles and neurosecretory areas.An action of the parasite at a distance, i.e. in the absence of contact of the roots with the ganglia, also occurs. It is especially marked as early as 1 month after infestation by a degeneration of the secretory perikarya.A thin sheath of connective tissue is sometimes visible between the growing roots and the VGM of juvenile crabs. However, the existence of that tissue cannot be definitely attributed to a host defense reaction.No effect of the developing parasite on the already differentiated external sex characters of the host has been noticed within the limits of the experiments.

Distribution, metabolism and biological activity of deoxycorticosterone in the central nervous system

1975 ◽  
Vol 88 (1) ◽  
pp. 1-14 ◽  
Author(s):  
I. Kraulis ◽  
G. Foldes ◽  
H. Traikov ◽  
B. Dubrovsky ◽  
M.K. Birmingham
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Biological Activity ◽  
The Central Nervous System
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