Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 15-azasteroid, 1,10,11,11a-tetrahydro-11a-methyl-2H naphth (1,2-g)indol-7-o1, inhibits the growth of the cell culture lines KB and L-M as well as several strains of bacteria. The inhibition of growth is reversed following removal of the steroid from the growth medium. Using in vitro grown L-M cells, the compound inhibited the transport of amino acids and uracil. The action was non-detergent like and at least 100 times more effective in terminating metabolite transport than sodium azide. The azasteroid inhibited the oxidation of glutamate in isolated rat liver mitochondria. The oxidation of succinate was not effected by the azasteroid alone but in the presence of glutamate, the azasteroid uncoupled the oxidation of succinate from the ADP-ATP control. It is suggested that the azasteroid may be acting directly on the electron transport system and/or acting indirectly through membrane perturbations which disrupts the electron transport process.
Steroids 1976 Oct
PMID:15-Azasteroid blockage of cell permeability and mitochondrial respiration. 100 23

The preovulatory gonadotropin surge is induced by progesterone in the cycling female rat or in the ovariectomized estrogen-treated female rat after adequate estrogen-priming activity is present. The source of progesterone under physiological conditions could be the ovary and/or the adrenal. Since the GnRH neuron does not possess estrogen and progesterone receptors, its function is modulated by other CNS neurotransmitters and neurosecretory products. Among these, excitatory amino acids (EAAs) have now been shown to play an important role in the regulation of pulsatile gonadotropin release, induction of puberty and preovulatory and steroid-induced gonadotropin surges. Glutamate, the major endogenous EAA exerts its action through ionotropic and metabotropic receptors. The ionotropic receptors consist of two major classes, the NMDA (N-methyl-D-aspartate) and non-NMDA: kainate and AMPA (DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. EAA receptors are found in hypothalamic areas involved with reproduction. While both NMDA and non-NMDA receptors are involved in the regulation of LH secretion, the NMDA receptors appear to be involved with the regulation of puberty and FSH secretion as well. Steroids increase the release rates of glutamate and aspartate in the preoptic area during the gonadotropin surge. Steroids may also regulate the hypothalamic AMPA receptors.
 ...
PMID:Glutamate: a major neuroendocrine excitatory signal mediating steroid effects on gonadotropin secretion. 762 74

Excitatory amino acids (EAAs), such as glutamate and aspartate, are found in large concentrations in presynaptic boutons of a variety of important hypothalamic nuclei, including the arcuate nucleus, supraoptic nucleus, suprachiasmatic nucleus, paraventricular nucleus, organum vasculosa of the lamina terminalis (OVLT) and preoptic area (POA). Likewise, the different ionotropic/metabotropic EAA receptor subtypes are found in the same regions of the hypothalamus although there are differences in their individual patterns of localization. Furthermore, there is evidence supporting the presence of ionotropic N-methyl-D-aspartate (NMDA) receptors and non-NMDA (kainate and AMPA) receptors in the anterior lobe, intermediate lobe and posterior lobe of the pituitary. The majority of work to date has focused on the role of EAAs in the control of LH secretion. Administration of glutamate, NMDA, kainate or AMPA leads to rapid LH release mediated through the stimulation of hypothalamic GnRH release. The major site of NMDA action appears to be the OVLT/preoptic area--where GnRH cell bodies reside, whereas AMPA and kainate have been suggested to act primarily at the arcuate nucleus/median eminence--the site of GnRH nerve terminals. There is evidence that some of the effects of glutamate on GnRH release may involve activation of the novel neurotransmitter nitric oxide and possibly catecholamines. The physiological importance of EAAs in the control of LH surge expression is evidenced by the findings that the steroid-induced LH surge in ovariectomized animals and the preovulatory LH surge in cycling animals and in PMSG-primed animals is blocked by treatment with specific NMDA receptor antagonists, or non-NMDA receptor antagonists. EAAs also appear to be important in regulating the normal pulsatile pattern of LH release as evidenced by the finding that both the NMDA antagonist, AP5, and the AMPA/kainate antagonist, DNQX, lower mean LH levels, LH pulse amplitude and LH pulse frequency in the adult ovariectomized rat. A role for NMDA receptors in the achievement of puberty has been suggested since activation of NMDA receptors has been shown to advance the time of vaginal opening in the immature female rat, while kainate and DNQX were without effect. Steroids have been reported not to affect NMDA receptor binding in the hypothalamus; however, steroids appear to up-regulate AMPA receptor GluR1 subunit levels and non-NMDA receptor binding in the hypothalamus. Steroids also increase the release rates of glutamate and aspartate in the POA during the steroid-induced LH surge in the ovariectomized adult rat.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Glutamate: a major excitatory transmitter in neuroendocrine regulation. 789 26

We have previously shown that both epidural administration and microinjection of methylprednisolone (MP) produces neuronal hyperexcitability in the murine spinal cord in vivo. In this study, the whole-cell patch-clamp technique was used to describe and characterize MP-induced neuronal hyperexcitability. Exposure of 10- to 18-day old dissociated spinal cord cultures to 65 microM-8 mM MP caused a concentration-dependent increase in the firing rate. MP (1 mM) increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and spontaneous inhibitory postsynaptic currents (sIPSCs). The amplitude of the sEPSCs was also increased in response to 1 mM MP, whereas sIPSCs became smaller in size in the presence of MP. MP (1 mM) reduced the amplitude of the gamma-aminobutyric acid (GABA)-induced currents, whereas it increased the amplitude of the glutamate-induced currents. And finally; MP (1 mM), by itself, did not change the overall postsynaptic membrane conductance. These observations suggest that (1) MP can act as an excitatory agent in vitro, (2) it can act at the presynaptic as well as the postsynaptic level, and (3) it affects spinal cord neurons by influencing the ligand-gated (GABA and glutamate) channels.
Steroids 1996 Jun
PMID:Effects of methylprednisolone on the GABA- and glutamate-induced currents: relevance to glucocorticoid-induced neurotoxicity and brain aging. 877 98

Glutamate is an important excitatory signal in the hypothalamus for the steroid-mediated preovulatory gonadotropin surge. Steroids may exert this action by regulating glutamate receptor levels or glutamate release, or both. Work in our laboratory found no changes in NMDA and kainate receptor binding in the hypothalamus of castrated or castrated plus steroid-replaced male and female rats. Likewise, we found that NMDA and kainate binding did not change over the onset of puberty in the female rat. A competitive quantitative RT-PCR assay using exogenous internal standards was used to measure NMDAR1, GluR1, and beta-actin mRNAs levels. NMDAR1 and GluR1 expression was examined in the preoptic hypothalamic area and in the medial basal hypothalamus at Postnatal Days 10, 15, 20, 25, 30, 32, 34, 36, 40, and 63. A transient increase in GluR1 mRNA levels in the preoptic hypothalamic area was observed on Day 20, with all other time points showing comparable levels. NMDAR1 levels in the POA and medial basal hypothalamus did not change significantly at any of the time points; in contrast, however, AMPA receptor binding levels were increased in the hypothalamus at the time of puberty in the female rat. Thus, in addition to the previously reported elevation of glutamate release rates in the hypothalamus at the time of puberty, AMPA receptors may also be elevated and play a role in mediating glutamate regulatory effects on the timing of puberty in the female rat.
Steroids
PMID:Excitatory amino acid receptors and puberty. 961 83

There is considerable evidence that although estradiol may trigger the preovulatory surge of gonadotropins, progesterone is required for its full magnitude and duration and that glucocorticoids bring about selective follicle-stimulating hormone release. The luteinizing hormone-releasing hormone (LHRH) neuron does not have steroid receptors and is regulated by excitatory amino acid neurotransmission. Steroids do not appear to modulate excitatory amino acid receptors directly but increase release of glutamate in the preoptic area. This may be due to the suppression by steroids of the enzyme glutamatic acid decarboxylase67 that converts glutamate into GABA. NMDA receptors colocalize with nitric oxide synthase-containing neurons that surround the LHRH neurons in the preoptic area and intersect the LHRH fibers in the median eminence. Other potential novel pathways of LHRH release that are currently being explored include carbon monoxide generated by the action of heme oxygenase-2 on heme molecules and bradykinin acting via bradykinin B2 receptors.
Steroids
PMID:Neuroendocrine mechanisms underlying the control of gonadotropin secretion by steroids. 961 80

Estrogens have demonstrable neuroprotective effects. This fact has lead to the proposed use of estrogens for the prevention and/or treatment of Alzheimer's disease. The exact protective mechanism estrogens provide is not fully understood. In this report, a potential non-genomic mechanism for estratrienes involving alterations in membrane fluidity was studied. Steroids, such as estrogen, are known to be membrane-active and can alter the lipid packing. In this study we used fluorescent methodologies to address the effect of naturally occurring steroids (17alpha and 17beta-estradiol, testosterone, and progesterone) and new estratriene analogs on membrane fluidity using liposomes and HT-22 hippocampal cells. The study's results indicate steroids, based on the estratriene nucleus, can modulate lipid packing as evidenced by (1) decreased membrane fusion events and (2) decreased membrane fluidity. The effects on the membrane were both time and concentration dependent. It was also demonstrated through rational design estratriene analogs can be synthesized with enhanced membrane effects. Finally, in a glutamate-induced toxicity HT-22 model, we also demonstrated cellular protection with the estratriene-based molecules and analogs. The data suggest the plethora of cellular actions of estrogens may relate to or be influenced by membrane effects of the steroid.
 ...
PMID:Membrane fluidity effects of estratrienes. 1140 93

The following review focuses on neurobiological mechanisms responsible for the individual recognition of the olfactory signature of the young by the ewe at parturition. Steroids and vaginocervical stimulation are responsible for neurochemical and electrophysiological changes within the olfactory bulb that are part of the learning mechanisms of the individual lamb odour, thus allowing the establishment of a selective bond between the ewe and her lamb. There is an increase in the number of mitral cells, the principal cells of the olfactory bulb that respond to lamb odours, which is associated with increased release of glutamate and gamma-aminobutyric acid from the dendrodendritic synapses between the mitral and granule cells. The relation between the release of the two transmitters after birth suggests an increased efficacy of glutamate evoked gamma-aminobutyric acid release. Parturition is also accompanied by increased oxytocinergic, cholinergic and noradrenergic neurotransmitter release that are essential for selective recognition of lambs. These increases in transmitter release depend on maternal experience, so that greater amounts have been found in multiparous than primiparous ewes. Therefore maternal experience seems to induce a neural maturation process that facilitates effective transmitter release in the olfactory bulb.
 ...
PMID:Neurobiological mechanisms involved in recognition of olfactory signature of the young in sheep. 1213 38

Although estradiol (E2) triggers phasic increases in LH-releasing hormone (LHRH) synthesis and release, the neurocircuitry responsible for these changes is unclear. We used an ovariectomized, E2-treated animal model to investigate the possibility that glutamate, through N-methyl-D-aspartate (NMDA) receptors (NMDAR), communicates E2 signals to LHRH neurons. A neuroanatomical analysis of the region containing LHRH neurons revealed that approximately 80% of LHRH neurons in medial, but less than 40% in lateral, nuclei of the preoptic area contained NMDAR1 mRNA. Consistent with this distribution pattern, NMDA doubled LHRH mRNA levels in medial neurons, but increased them by less than 30% in cells of the lateral nuclei. Steroids did not alter NMDAR1 mRNA levels in LHRH neurons or change the percentage of LHRH neurons expressing the gene. Furthermore, in contrast to the regionalized effects of NMDA, E2 treatment increased LHRH mRNA levels to the same extent in medial and lateral neurons, and MK801 failed to block E2-induced changes in LHRH gene expression. These results demonstrate that glutamatergic signaling via NMDA receptors is direct and preferentially targets LHRH neurons in medial nuclei of the preoptic area. However, it is unlikely that NMDAR activation mediates E2-dependent increases in LHRH mRNA levels before the LH surge.
 ...
PMID:Glutamatergic signaling through the N-methyl-D-aspartate receptor directly activates medial subpopulations of luteinizing hormone-releasing hormone (LHRH) neurons, but does not appear to mediate the effects of estradiol on LHRH gene expression. 1244 11

Steroids influence neuronal function through binding to cognate intracellular receptors which may act as transcription factors in the regulation of gene expression. In addition, certain so-called neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially distinct 3alpha-reduced metabolites of progesterone and deoxycorticosterone are potent positive allosteric modulators of gamma-aminobutyric acid type A (GABA(A)) receptors. However, also classical steroid hormones such as 17beta-estradiol, testosterone and progesterone are neuroactive steroids because they may act as functional antagonists at the 5-hydroxytryptamine type 3 (5-HT(3)) receptor, a ligand-gated ion channel or distinct glutamate receptors. A structure-activity relationship for the actions of a variety of steroids at the 5-HT(3) receptor was elaborated that differed considerably from that known for GABA(A) receptors. Although a bindings site for steroids at GABA(A) receptors is still a matter of debate, meanwhile there is also evidence that steroids interact allosterically with ligand-gated ion channels at the receptor membrane interface. On the other hand, also 3alpha-reduced neuroactive steroids may regulate gene expression via the progesterone receptor after intracellular oxidation into 5alpha-pregnane steroids. Animal studies showed that progesterone is converted rapidly into GABAergic neuroactive steroids in vivo. Progesterone reduces locomotor activity in a dose-dependent fashion in male Wistar rats. Moreover, progesterone and 3alpha-reduced neuroactive steroids produce a benzodiazepine-like sleep EEG profile in rats and humans. During major depression, there is a disequilibrium of such 3alpha-reduced neuroactive steroids which is corrected by successful treatment with antidepressant drugs. Neuroactive steroids may further be involved in the treatment of depression and anxiety with antidepressants in patients during ethanol withdrawal. Studies in patients with panic disorder suggest that neuroactive steroids may also play a role in modulating human anxiety. Both the genomic and non-genomic effects of steroids in the brain may contribute to the pathophysiology of psychiatric disorders and the mechanisms of action of antidepressants. Neuroactive steroids affect a broad spectrum of behavioral functions through their unique molecular properties and may represent a new treatment strategy for neuropsychiatric disorders.
 ...
PMID:Neuroactive steroids: mechanisms of action and neuropsychopharmacological properties. 1251 9


1 2 3 Next >>