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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucocorticoids regulate the activity of the hypothalamic-pituitary-adrenal axis through both mineralocorticoid (MR) and glucocorticoid (GR) receptors in the hippocampus. In addition, glucocorticoids down-regulate hippocampal expression of MR and GR mRNA and protein, presumably decreasing their own effect. Marmosets are a New World primate characterized by extraordinarily high levels of circulating ACTH and cortisol. The relative glucocorticoid insensitivity of these animals to their massive levels of glucocorticoids was attributed to a decreased affinity of their GR for glucocorticoids, as well as a compromised ability of this receptor to transactivate glucocorticoid-responsive genes. The lack of mineralocorticoid excess, on the other hand, was attributed to a renal MR which responded poorly to cortisol, but normally to aldosterone. The purpose of this study was to examine MR and GR mRNA expression in the marmoset (Callithrix jacchus jacchus) hippocampus. Overall, steady state levels of both MR and GR mRNA were elevated in all of the hippocampal subfields of the marmoset, and this was obvious in rough comparisons with those of a typical glucocorticoid-sensitive Old World primate, the rhesus monkey (Macaca mulata). Notable were the extremely high levels of GR mRNA in the dentate gyrus and field CA3 of the marmoset. The GR mRNA density distribution of the marmoset also appeared to differ from that in the rhesus and from those previously reported in rats and humans. These findings suggest that there is a compensatory elevation of MR and GR mRNAs in the marmoset hippocampus, which appears to be the result of target tissue resistance to glucocorticoids and inappropriate down-regulation by the elevated, but ineffective, circulating cortisol.
Steroids 1996 Feb
PMID:Distribution of hippocampal mineralocorticoid and glucocorticoid receptor mRNA in a glucocorticoid resistant nonhuman primate. 875 Apr 35

For collection of saliva, cotton buds (Q-tips) were inserted into the guinea pig's cheek pouch, parallel with the cheek teeth. Within 5 min, sufficient fluid was collected for cortisol and testosterone measurements. In saline-treated animals, saliva cortisol and testosterone were about 15 ng/mL and 1.5 ng/mL, corresponding to plasma levels of 52 ng/mL and 5.9 ng/mL. Within 2-4 h after administration of 20 IU ACTH, saliva and plasma cortisol concentrations were strikingly elevated: saliva: 125 ng/mL (2 h), 157 ng/mL (4 h); plasma: 458 ng/mL (2 h), 736 ng/mL (4 h). This treatment did not influence testosterone in saliva, but reduced it in plasma (2.4 ng/mL (4 h)). In animals receiving 100 IU HCG, saliva testosterone remained unchanged, whereas its plasma levels were markedly raised (9.6 ng/mL (2 h), 12.5 ng/mL (4 h)). These results show that saliva cortisol offers promise as a noninvasive method of monitoring changes in guinea pig adrenocortical function. Saliva testosterone, on the other hand, does not correlate with plasma values; hence it cannot be used to assess testicular function in the guinea pig.
Steroids 1996 Nov
PMID:Saliva cortisol and testosterone in the guinea pig: measures for the endocrine function of adrenals and testes? 891 59

The transcription of steroid hydroxylase genes is controlled by ACTH and cAMP in the adrenal cortex. In most instances the regulation appears to rely on transcription factors traditionally not associated with cAMP-dependent gene expression. For the non-traditional factors it remains necessary to elucidate the coupling of increases in intracellular cAMP and cAMP-dependent protein kinase (PKA) activity to the function of these proteins. The bovine CYP17 gene, which encodes the steroid 17 alpha-hydroxylase, contains two discrete DNA elements within its promoter and upstream region (CRS1 and CRS2) that individually can confer cAMP responsiveness. The CRS1 element is a target for PKA signalling and for negative regulation via the protein kinase C signal transduction pathway. The homeodomain protein Pbx1 enhances CRS1-dependent transcription, but additional CRS1-binding proteins remain to be identified. Furthermore it is not known how PKA regulates the activity of Pbx1 or its possible binding partners. Closer to the promoter, the nuclear orphan receptors SF-1 and COUP-TF have overlapping binding sites in CRS2 and they bind in a mutually exclusive manner with very similar affinities; 8 and 10 nM, respectively. SF-1 stimulates whereas COUP-TF inhibits transcription from the bovine CYP17 promoter. Together, the data suggest that cAMP-dependent control of the amounts of the activator SF-1 vs. the repressor COUP-TF could influence CRS2-dependent transcription. In addition, PKA may influence the phosphorylation of SF-1, thus increasing its activity. In vitro, PKA will elicit phosphorylation of SF-1. However, although SF-1 can be immunoprecipitated from adrenocortical cells as a phosphroprotein, we have not been able to show cAMP-dependent increase in net phosphorylation in intact cells. More careful examination of individual phosphorylation sites in SF-1 may still reveal hormone- and cAMP-induced phosphorylation of SF-1.
Steroids 1997 Jan
PMID:Transcriptional regulation of the bovine CYP17 gene by cAMP. 902 13

Development of the human fetal adrenals is characterized by rapid growth and high levels of steroidogenic activity during the latter two-thirds of pregnancy. By midgestation, the human fetal adrenals are composed of two distinct cortical zones: the predominant fetal zone, which occupies 80-90% of the cortical volume and produces large amounts of the delta 5-steroid dehydroepiandrosterone sulfate, and the narrow definitive zone, which surrounds the fetal zone. Late in gestation, the peripheral portion of the fetal zone develops into a third, functionally distinct compartment, the transitional zone, which is the likely site of cortisol synthesis. Soon after birth, the adrenal cortex is remodeled and the fetal zone disappears. The adult cortical zones are thought to arise from the definitive zone, which persists postnatally. Development of the human fetal adrenals is regulated primarily by corticortropin (ACTH) secreted from the fetal pituitary. However, as ACTH is not a mitogen per se, its proliferative actions on human fetal adrenal cortical cells are thought to be mediated by autocrine/paracrine growth factors produced by adrenal cortical cells in response to ACTH. In addition, these growth factors appear to modulate the functional response of fetal adrenal cortical cells to ACTH. The roles of several growth factors, including the insulin like growth factors I and II (IGF-I and IGF-II), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), activin, inhibin, and the transforming growth factors alpha and beta (TGF-alpha and TGF-beta) have been examined. In cultured human fetal adrenal cortical cells, EGF, bFGF, and IGF-I and -II are mitogenic, whereas activin and TGF-beta inhibit proliferation. IGF-II, activin, and TGF-beta also modulate ACTH-stimulated steroidogenesis. Human fetal adrenal cortical cells express IGF-II, bFGF and the activin/inhibin subunits, and the abundance of mRNAs for each of these factors is up-regulated by ACTH, suggesting that these growth factors are autocrine/paracrine mediators of ACTH action. Thus, although human adrenal development is primarily regulated by ACTH, its actions appear to be mediated/modulated by a cohort of locally expressed growth factors, the net effect of which results in the unique growth and steroidogenic activity of the human fetal adrenal cortex.
Steroids 1997 Jan
PMID:Role of growth factors in the developmental regulation of the human fetal adrenal cortex. 902 17

The rate of steroid synthesis is regulated by the rate of transport of cholesterol to mitochondria. The transport process involves two elements of the cytoskeleton (microfilaments and intermediate filaments) and Ca2+/ calmodulin. Electron microscopy and immunofluorescence reveal that lipid droplets in which steroidogenic cholesterol is stored in the cytoplasm are tightly attached to vimentin intermediate filaments. Mitochondria are also attached to intermediate filaments. Ca2+/calmodulin is known to be essential for the steroidogenic response to ACTH and acts to increase transport of cholesterol to mitochondria. Ca2+/ calmodulin promotes phosphorylation of two important adrenal proteins: vimentin via its protein kinase and myosin light chain via the calmodulin-dependent light-chain kinase. In permeabilized adrenal cells Ca2+/calmodulin causes an ATP-dependent contraction of the cells. Phosphorylation of vimentin is known to cause breakdown of intermediate filaments. Electron microscopy reveals that actin filaments cross-link intermediate filaments in adrenal cells. It is proposed that ACTH has at least two second messengers, Ca2+/calmodulin and cAMP. Ca2+/calmodulin causes breakdown of vimentin filaments and activates a contractile event dependent on ATP and myosin light chain. These changes reorganize the cytoskeleton in such a way as to facilitate the interaction of lipid droplets with mitochondria, resulting in transport of cholesterol to these organelles and hence increased steroid synthesis.
Steroids 1997 Jan
PMID:The roles of calmodulin, actin, and vimentin in steroid synthesis by adrenal cells. 902 35

Using transgenic mice, we targeted SV40 T antigen and the bacterial neomycin resistance gene to steroidogenic tissues using a human P450 cholesterol side-chain cleavage promoter. Expression of SV40 T antigen resulted in adrenocortical tumors. Adrenocortical cell lines from one of these tumors (ST5R) was previously characterized. We have now obtained clonal lines from the second more differentiated tumor. After dispersion of the left adrenal tumor, ST5L parental cells were selected with G418 and subcloned. The resulting adrenocortical subcloned cell lines are more highly differentiated than those cell lines resulting from the right adrenal tumor (ST5R). ST5L cell lines secrete progesterone and corticosterone to varying degrees, whereas ST5R cells secrete only progesterone. One of the clonal cell lines, ST5Lc16, expresses both P450c11 beta and P450c11AS mRNAs, which normally are regionally distributed in different zones of the adrenal cortex. Thus, ST5Lc16 cells may be progenitor cells for both glomerulosa and fasciculata cells and may provide clues to the cellular and molecular events leading to the differentiation of the glomerulosa and the fasciculata-reticularis. Other ST5Lc cell lines are more representative of the fasciculata-reticularis, because they express P450c11 beta mRNA and secrete corticosterone, and they neither express P450c11AS mRNA nor do they secrete aldosterone. All cell lines also have 21-hydroxylase activity, but none express P450c21, indicating that some other, as yet unidentified, enzyme has this activity. In all cell lines, steroid secretion is regulable by cAMP stimulation but not by ACTH stimulation. All ST5L cell lines also express mouse renin-1 mRNA. In addition to their utility in studies of adrenal steroidogenesis, these cell lines may also be useful in studying the etiology of adrenocortical tumors.
Steroids 1997 Feb
PMID:Characterization of adrenocortical cell lines produced by genetically targeted tumorigenesis in transgenic mice. 905 83

Insulin and the insulin-like growth factors (IGFs) have multiple role in gene expression in steroidogenic cells. We investigated the regulation of steroidogenic enzyme gene expression by insulin and IGF-I in primary cultures of human adrenocortical cells from donors of ages 19-77 years. The effects of insulin and IGF-I observed here were independent of age and sex of the donor. After 5 days in serum-containing medium, cultures were exposed to insulin or IGF-I together with cyclic AMP analogs or ACTH in serum-free defined medium. Insulin and IGF-I at physiological concentrations increased mRNA levels for 17 alpha-hydroxylase and type II 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) in the absence of cyclic AMP or ACTH. They had lesser effects on 21-hydroxylase and cholesterol side-chain cleavage enzyme mRNA levels and were3 without effect on 11 beta-hydroxylase mRNA. All steroidogenic enzyme mRNAs were strongly increased by cyclic AMP or ACTH, and this increase was potentiated by insulin or IGF-I. These effects of insulin and IGF-I were accompanied by decreases in the ratio of dehydroepiandrosterone/cortisol synthesized from pregnenolone by the cultures. Induction of steroidogenic enzyme genes in adult human adrenocortical cells by insulin and IGF-I is unlikely to occur by means of a cyclic AMP-dependent mechanism. These data increase the evidence for an important regulation of steroidogenesis by these hormones.
Steroids 1997 Feb
PMID:Induction of steroidogenic enzyme genes by insulin and IGF-I in cultured adult human adrenocortical cells. 905 86

The regulation of the hypothalamo-pituitary-adrenal (HPA) axis in the operative and perioperative period of major surgical procedures is necessary for successful adaption to surgical stress. We report evidence on an altered response of HPA axis regulation in patients who underwent coronary artery bypass grafting (CABG) surgery. Plasma levels of adrenocorticotropin (ACTH), beta-endorphin, and cortisol were determined with radio-immune assay in 50 males for elective CABG surgery. The patients received general anesthesia using a balanced technique with sufentanil, isoflurane, and midazolam. Pre- and intraoperatively, there was no significant increase in plasma cortisol, ACTH, and beta-endorphin levels. On the evening of surgery, all plasma hormone levels were increased. On the evening of the first and second postoperative day, plasma ACTH and beta-endorphin levels returned to the preoperative baseline values. During the same time interval, plasma cortisol levels were significantly elevated and remained high until the end of the study period (p < 0.001). Our results indicate an altered regulation of the HPA axis in the postoperative period of patients after CABG surgery, as they are compatible with similar results in patients after major abdominal surgery, burned patients, and critically ill patients. Therefore, it is assumed that the finding of a postoperative dissociation between ACTH and cortisol is a result of the severity of perioperative adaptive mechanisms rather than of the specific conditions related to cardiac surgery.
Steroids 1997 Nov
PMID:Postoperative dissociation of blood levels of cortisol and adrenocorticotropin after coronary artery bypass grafting surgery. 936 7

In this paper, we studied the effect of heme availability on corticosterone and aldosterone synthesis in rat adrenal. We found that hemin stimulated corticosterone and aldosterone production in adrenal homogenates in a dose-dependent fashion. Hemin administration to rats also provoked an increase in both corticosterone and aldosterone content in adrenal. 3,5-Diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC), an inhibitor of liver ferrochelatase activity, was able to inhibit this enzyme in rat adrenal. This resulted in an impairment of heme concentration and consequently adrenal ALA-synthase and porphyrin content were increased. Thus, it was proven that DDC inhibits heme biosynthesis in adrenal as it does in liver. In vivo experiments with rats showed that DDC was able to partially blocked ACTH-mediated corticosterone and aldosterone production while hemin administration was able to partially restore it. These data indicate that heme availability affects steroid biosynthesis in rat adrenal.
Steroids 1997 Dec
PMID:Heme availability affects corticosterone and aldosterone biosynthesis in rat adrenal. 943 40

In the present paper, we report that an inositolphosphoglycan (IPG), derived from a Trypanosoma cruzi glycoinositolphosphoceramide (LPPG), is able to inhibit ACTH-mediated accumulation of a glucocorticoid, cortisol, in calf adrenocortical cells. This IPG is also able to inhibit the stimulation by ACTH of the production of the main glucocorticoid, corticosterone and the main mineralocorticoid, aldosterone, in rat adrenocortical cells. Nitrous acid deamination confirmed that IPG is responsible for this inhibition. In order to study the involvement of glycosylphosphatidylinositol (GPI) in ACTH response in rat adrenal cortex, the activation of a phospholipase that hydrolyzes GPI (GPI-PLC) was evaluated. It was found that the release of alkaline phosphatase, a GPI-anchored enzyme, to the extracellular medium is increased in rat adrenocortical cells by ACTH treatment. In addition, ACTH stimulates the release of ceramide from the glycoinositolphosphoceramide purified from T. cruzi. These data suggest that ACTH activates a GPI-PLC in rat adrenal cortex, which is in agreement with our previous data in calf adrenocortical cells; thus, the hydrolysis of GPI provoked by ACTH takes place in different mammals and the IPG released could inhibit ACTH-mediated synthesis of aldosterone, corticosterone and cortisol.
Steroids 1998 Feb
PMID:ACTH-mediated glucocorticoid and mineralocorticoid production is inhibited by an inositolphosphoglycan and a glycosylphosphatidylinositol-phospholipase C is activated by the hormone in mammalian adrenocortical cells. 951 15


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