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Biomedical subjects

H S Choi

Publications and source records attributed to H S Choi.

At least 91 records · Page 5Linked to original sources
PubMed1999

The role of sarcolemmal Ca2+-ATPase in the regulation of resting calcium concentration in rat ventricular myocytes.

1. The aim of this work was to investigate the role of sarcolemmal Ca2+-ATPase in rat ventricular myocytes. We have measured intracellular Ca2+ concentration ([Ca2+]i) using indo-1. The actions of the ATPase inhibitor carboxyeosin were studied. 2. Carboxyeosin increased resting [Ca2+]i and the magnitude of the systolic Ca2+ transient and slowed the rate of its relaxation by 5 %. 3. Carboxyeosin increased the magnitude of the caffeine-evoked increase in [Ca2+]i and slowed its relaxation by 20 %. Removal of extracellular Na+ slowed the rate constant by 80 %. When Na+ was removed in a carboxyeosin-treated cell, the caffeine-evoked increase in [Ca2+]i did not decay. 4. Carboxyeosin increased the integral of the Na+-Ca2+ exchange current activated by caffeine. This is, in part, due to an increase in sarcoplasmic reticulum Ca2+ content. 5. When extracellular Na+ was removed, there was a transient increase in [Ca2+]i which then decayed. The rate of this decay was slowed by carboxyeosin by a factor of about four. The residual decay could be abolished with caffeine. 6. In the absence of extracellular Na+, increasing extracellular Ca2+ concentration ([Ca2+]o) elevated [Ca2+]i. In carboxyeosin-treated cells, [Ca2+]i was much more sensitive to [Ca2+]o. 7. These results demonstrate the role of a carboxyeosin-sensitive Ca2+-ATPase in the control of resting [Ca2+]i and the reduction in [Ca2+]i following an increase in [Ca2+]i.

Animals↗
PubMed1999

Effects of water extract of 1:1 mixture of Phellodendron cortex and Aralia cortex on polyol pathway and oxidative damage in lenses of diabetic rats.

Enhanced activity of the polyol pathway and oxidative damage have been implicated in the pathogenesis of diabetic cataract. We decided to investigate whether these changes in diabetic lenses could be prevented by the water extract of Phellodendron cortex and Aralia cortex (P55A). Aldose reductase activity was inhibited significantly by the treatment with P55A. Consequently, it caused a dramatic reduction in the high sorbitol contents observed in the lenses of diabetic rats. In addition, the greatly elevated content of thiobarbituric acid reactive substances (TBARS) and carbonylated protein in diabetic rats were reduced by P55A treatment. These results suggest that P55A extract exerts an antioxidant effect by reducing lipid peroxidation and protein carbonylation as well as having an inhibitory action against aldose reductase in the lenses of diabetic rats.

Aldehyde Reductase↗
PubMed1999

Inhibition of S6 kinase by rapamycin blocks maturation of Rana dybowskii oocytes.

Studies were carried out to define the hormone-induced signal transduction pathway during maturation of Rana dybowskii oocytes. Rapamycin, a specific inhibitor of S6 kinase, blocked progesterone-induced oocyte germinal vesicle breakdown (GVBD) in a dose-dependent manner indicating that S6 kinase is required for meiotic maturation of Rana oocytes. Addition of rapamycin within 3 h, but not 6 h, of progesterone treatment inhibited GVBD. In contrast, cycloheximide, a general protein synthesis inhibitor, blocked GVBD even when added 9 h after progesterone addition. A twofold increase in S6 kinase activity occurred within 1 h of progesterone stimulation and rapamycin inhibited this activity. Rapamycin also suppressed, in a dose-dependent manner, progesterone-induced protein synthesis during the first 12 h of culture but less effectively later. Histone H1 kinase activity (maturation-promoting factor, MPF) was observed in oocyte extracts at two different times (between 6 and 9 h and at 24 h) following progesterone stimulation. Rapamycin blocked H1 kinase activity between 6 and 9 h of culture but not that observed at 24 h. In contrast, cycloheximide suppressed progesterone-induced H1 kinase activity as well as protein synthesis throughout the course of incubation. Such results indicate that rapamycin and cycloheximide have common and unique effects on oocyte maturation and suggest that progesterone-induced S6 kinase activity is closely associated with induction of protein synthesis and activation of MPF during oocyte maturation. Results in Rana contrast with those obtained in Xenopus where rapamycin inhibited S6 kinase but failed to inhibit GVBD or protein synthesis. Differences in the response of Rana and Xenopus oocytes to rapamycin are discussed in relation to seasonal, biochemical, and species variations.

Animals↗
PubMed1999

NMDA receptor antagonists enhance 5-HT2 receptor-mediated behavior, head-twitch response, in PCPA-treated mice.

Previous work in our laboratory has shown that the N-methyl-D-aspartate (NMDA) receptor antagonists, AP-5, CPP, MK-801, ketamine, dextrorphan and dextromethorphan cause a pronounced enhancement of 5-hydroxytryptamine (5-HT)-induced head-twitch response (HTR) in intact mice, suggesting the involvement of NMDA receptors in the glutamatergic modulation of serotonergic function at the postsynaptic 5-HT2 receptors. The purpose of this study was to extend our previous work on the behavioral interaction between glutamatergic and serotonergic receptors. In the present study, both competitive (AP-5 and CPP) and noncompetitive (MK-801, ketamine, dextrorphan and dextromethorphan) NMDA receptor antagonists markedly enhanced 5-HT-induced selective serotonergic behavior, HTR, in p-chlorophenylalanine (PCPA)-treated mice which were devoid of any involvement of indirect serotonergic function, to establish the involvement of the NMDA receptor in 5-HT-induced HTR at the postsynaptic 5-HT2 receptors. In addition, the enhancement of 5-HT-induced HTR was inhibited by a dopamine agonist, apomorphine, NMDA receptor antagonist, NMDA and a serotonin 5-HT2 receptor antagonist, cyproheptadine, in PCPA-treated mice. Therefore, the present results support our previous conclusion that the NMDA receptors play an important role in the glutamatergic modulation of serotonergic function at the postsynaptic 5-HT2 receptors.

Animals↗
PubMed1999

Experience of 1446 rectal cancer patients in Korea and analysis of prognostic factors.

In order to investigate the changing pattern of rectal cancers in Korea and to identify prognostic factors, we investigated the case histories of 1446 rectal cancer patients who had received surgical treatment. During the study period there were trends toward a decrease in the ratio of rectal cancer to colon cancer, earlier detection (more Dukes' stages A and B and fewer C), a decrease in the number of abdominoperineal resections, and an increase in the number of sphincter-preserving operations. Univariate analysis of prognostic factors showed that gender, obstruction symptoms, preoperative serum carcinoembryonic antigen (CEA) level, tumor size, depth of bowel wall invasion, lymph node metastases (presence and number), tumor differentiation, operative method, and date of operation were significant, but age, symptom duration, and tumor location were not. The use of sphincter-saving operations did not adversely affect the clinical outcome. Multivariate analysis showed lymph node metastasis factor to be the most significant factor (P < 0.001); the depth of bowel wall invasion, differentiation, CEA level, and date of operation were also significant (0.001 < P < 0.05). This study shows that although anatomical extent of disease (depth of invasion and lymph node metastasis) is the most reliable prognostic predictor in rectal cancer, other factors such as preoperative CEA level and tumor differentiation also provide important information on the outcome and use of an anal-preserving operation does not adversely affect the patient survival.

Adult↗
PubMed1999

The effects of inhibition of the sarcolemmal Ca-ATPase on systolic calcium fluxes and intracellular calcium concentration in rat ventricular myocytes.

The effects of carboxyeosin, an inhibitor of the sarcolemmal Ca-ATPase, were studied on intracellular Ca and membrane currents in isolated rat ventricular myocytes. In the absence of carboxyeosin, 150-ms-duration depolarizing pulses from -40 to 0 mV resulted in an L-type Ca current on depolarization and a Na-Ca exchange "tail" current on repolarization. The calculated entry of Ca on the L-type current was 1.3 times greater than the efflux via the Na-Ca exchange. The addition of carboxyeosin (20 microM) resulted in either an increase of the Na-Ca exchange current or a decrease of the L-type Ca current such that the Ca entry and efflux were exactly equal. These results suggest that, under control conditions, a carboxyeosin-sensitive Ca-ATPase contributes about 24% of the total Ca efflux from the cell and, therefore, that the sarcolemmal Ca-ATPase has a significant role in regulation of sarcolemmal Ca fluxes.

Animals↗
PubMed1999

Proliferation not apoptosis as a prognostic indicator in retinoblastoma.

The balance between proliferation and cell death is the major determinant of tumour growth. We analysed the proliferative and apoptotic indices (PI and AI, respectively) of 33 children with retinoblastoma. PI and AI were assessed by immunohistochemistry for Ki-67 antigen and TUNEL staining, respectively. The mean PI was 21.0+/-21.1%, and higher PI was associated with more advanced tumour stage (P<0.0001) and poor clinical outcome (P<0.05). Patients in whom amplified N-myc oncogene was found (n=6) determined by the multiplex polymerase chain reaction tended to have a higher PI (37.6+/-27.2%) than those without amplified N-myc (n=27; PI=17.3+/-18.1). A PI value of over 40% was clearly associated with an unfavourable prognosis. The AI, however, did not correlate with any of the other variables analysed. The findings suggest that proliferation, but not apoptosis, is of critical significance in retinoblastoma biology. PI, as determined by the Ki-67 antigen labelling index, seems to be a relevant histopathological parameter that can predict the clinical outcome of retinoblastoma.

Apoptosis↗
PubMed1999

Postoperative pelvic lymphocele: treatment with simple percutaneous catheter drainage.

PURPOSE: To evaluate the effectiveness of simple percutaneous catheter drainage in the treatment of postoperative lymphocele. MATERIALS AND METHODS: Percutaneous catheter drainage of 23 symptomatic lymphoceles was performed with ultrasonographic (US) guidance in 20 patients who had undergone radical pelvic lymphadenectomy because of uterine malignancy. All lymphoceles were diagnosed on the basis of biochemical and cytologic findings in aspirated fluid. The drainage catheter was removed when the amount of daily drainage was less than 10 mL per day and when the lymphocele was seen at imaging to have resolved. Follow-up US was performed at 1, 3, and 6 months after catheter removal. The results were classified as success, partial success, or failure. RESULTS: Lymphoceles ranged in size from 5 x 4 x 3 to 25 x 10 x 10 cm. Mean total drainage volume was 2,012 mL (range, 300-17,240 mL). Fluid from 10 lymphoceles (43%) was positive at Gram staining and bacteriologic culture; fluid from 13 (57%) was sterile. Duration of catheter drainage was 3-49 days (mean, 22 days). Twenty (87%) lymphoceles resolved completely; three (13%) recurred. Two recurrent lymphoceles were again treated with percutaneous catheter drainage; the third resolved spontaneously 5 months after catheter removal. Successful treatment was ultimately achieved in all patients. Postprocedural complications occurred in four patients. One had a secondary infection of lymphocele; one, catheter dislodgment; and two, skin infection at the site of catheter insertion. CONCLUSION: Percutaneous catheter drainage is safe and effective for treatment of symptomatic postoperative lymphoceles.

Catheterization↗
PubMed1999

Effect of isoprenaline, carbachol, and Cs+ on Na+ activity and pacemaker potential in rabbit SA node cells.

Effects of isoprenaline, carbachol, and Cs+ on intracellular Na+ activity (a(i)Na) and spontaneous action potentials were studied in multicellular and single cell preparations isolated from rabbit sinoatrial (SA) nodes. a(i)Na was measured with double-barreled Na+-selective microelectrodes and the fluorescent Na+-indicator sodium-binding benzofuran isophthalate (SBFI). In spontaneously beating cells, aiNa measured with Na+-selective microelectrodes and SBFI were 4.5 +/- 1.2 mM (means +/- SD, n = 21) in multicellular preparations and 4.0 +/- 1.1 mM (n = 16) in single cells, respectively. Measurements of a(i)Na with microelectrodes showed that isoprenaline increased a(i)Na from 4.7 +/- 1.2 to 5.5 +/- 1.6 mM (n = 16, P < 0.01) and shortened the action potential cycle length (ACL) from 338 +/- 46 to 269 +/- 35 ms (n = 16, P < 0.01). However, increasing the action potential rate by pacing produced a much smaller increase in a(i)Na. Changes in a(i)Na and ACL produced by isoprenaline were blocked by Cs+. The selective hyperpolarization-activated inward current (If) blocker ZD-7288 decreased a(i)Na from 5.2 +/- 1.0 to 4.6 +/- 1.3 mM (n = 4, P < 0.01) and prolonged ACL from 394 +/- 20 to 553 +/- 68 ms (n = 4, P < 0.01). The If blocker substantially inhibited the increase in a(i)Na produced by isoprenaline. Carbachol and Cs+ decreased aiNa from 4.6 +/- 1.4 to 3.9 +/- 1.2 mM (n = 15, P < 0.01) and from 4.9 +/- 1.0 to 3.9 +/- 1.3 mM (n = 18, P < 0.01), respectively. In addition, carbachol and Cs+ prolonged ACL from 345 +/- 44 to 587 +/- 100 ms (n = 15, P < 0.01) and from 353 +/- 30 to 464 +/- 87 ms (n = 18, P < 0.01), respectively. However, carbachol and Cs+ almost did not change a(i)Na when SA node cells became quiescent in a 25.4 mM extracellular K+ concentration. The results suggest that isoprenaline, ZD-7288, carbachol, or Cs+ might have changed a(i)Na and action potential rate by possibly stimulating or inhibiting If carried by Na+. Measurements of a(i)Na with SBFI showed that isoprenaline, carbachol, and Cs+ produced a(i)Na changes that were similar to those measured with the microelectrodes.

Action Potentials↗
PubMed1999

Protopanaxatriol ginsenosides inhibit glucose uptake in primary cultured rabbit renal proximal tubular cells by arachidonic acid release.

Ginsenosides are involved in protective action against renal dysfunction and the regulation of renal functions. However, the effects of ginsenosides on glucose reabsorption are not yet known in renal proximal tubular cells. The aim of this study was to examine the effects of ginsenosides, protopanaxadiol (PD) saponin and protopanaxatriol (PT) saponin, on alpha-methyl-D-glucopyranoside (alpha-MG) uptake and its mechanism of action in primary cultured rabbit renal proximal tubular cells (PTCs). The alpha-MG uptake was inhibited by 90% by 0.5mM phloridizin and by removal of Na+ in the PTCs. These are typical characteristics described for the proximal tubule. To determine the time- and dose-dependent effects of PD and PT saponins on alpha-MG uptake, PTCs were incubated with different concentrations of PD and PT saponins (10-100 microg/ml) and for different time periods (from 10 min to 24 h). PT saponin (>/=50 microg/ml) from 30 min inhibited alpha-MG uptake; however, PD saponin did not alter the alpha-MG uptake at any doses and time periods. In the kinetic analysis of alpha-MG uptake, PT saponin produced a significant decrease in Vmax. The PT saponin induced inhibition of alpha-MG uptake was blocked by mepacrine, a phospholipase A2 inhibitor. In addition, PT saponin increased [3H] arachidonic acid release by 218% of that of control, and this effect was also completely blocked by mepacrine. In conclusion, PT saponin inhibited, in part, alpha-MG uptake through the phospholipase A2 signal pathway in primary cultured rabbit renal PTCs.

Animals↗
PubMed1999

Gonadotropin stimulation of pituitary adenylate cyclase-activating polypeptide (PACAP) messenger ribonucleic acid in the rat ovary and the role of PACAP as a follicle survival factor.

Pituitary adenylate cyclase-activating polypeptide (PACAP), a novel neuropeptide with considerable homology to vasoactive intestinal peptide and GH-releasing hormone, exists in two biologically active forms, PACAP-38 and -27. The presence of PACAP in the ovary has been demonstrated, where it stimulates steroidogenesis and cAMP accumulation in cultured granulosa cells. In the present study, gonadotropin regulation of PACAP gene expression was examined in PMSG/human (h)CG-treated immature rat ovaries and cultured preovulatory follicles. Northern blot analysis of ovaries obtained from PMSG/hCG-treated immature animals revealed the transient induction of PACAP transcripts by hCG, reaching a maximum at 6 h. The major cell types expressing PACAP messenger RNA were granulosa cells of preovulatory follicles and some theca/interstitial cells. In preovulatory follicles cultured in serum-free medium, PACAP transcripts were transiently induced by LH and FSH, reaching a maximum 6-9 h after stimulation in granulosa cells but not in theca cells. Treatment with cycloheximide or alpha-amanitin abolished LH-induced PACAP transcripts, indicating that new protein synthesis and transcription are necessary. Treatment with MDL-12,330A, an inhibitor of adenylate cyclase, inhibited LH-induced PACAP messenger RNA, and forskolin mimicked the LH action, implying the role of adenylate cyclase activation. In contrast, treatment with chelerythrine, an inhibitor of protein kinase C, and 2-O-tetradecanol-phorbol-13-acetate had no effect. We further tested the role of PACAP in follicle apoptosis using apoptotic DNA fragmentation analysis. Treatment with PACAP-38 suppressed follicle apoptosis in a dose-dependent manner. Moreover, the LH suppression of follicle apoptosis was partially blocked by cotreatment with PACAP-38 antagonist, indicating mediation by endogenous PACAP-38. These results suggest that PACAP, transiently induced by the gonadotropin surge, could be a local regulator of a number of events and may act as a follicle survival factor during the periovulatory period.

Adenylyl Cyclases↗
PubMed1999

Peutz-Jeghers syndrome: a new understanding.

Peutz-Jeghers syndrome is an autosomal dominant inherited disorder characterized by hamartomatous polyps in the small bowel and mucocutaneous pigmentation. Patients with Peutz-Jeghers syndrome often present as surgical emergencies with complications of the polyps, such as intussusception, bowel obstruction and bleeding. Furthermore, repeated operations may be needed in some patients, which may result in short bowel syndrome. Although early reports did not demonstrate a predisposition to cancer in patients with this syndrome, more recent studies have described an increased risk for both gastrointestinal and extra-gastrointestinal cancers. Women with the Peutz-Jeghers syndrome have the extremely high risk for breast and gynecologic cancer. Recently, Peutz-Jeghers syndrome susceptibility gene, encoding the serine threonine kinase STK11 (also called LKB1), was identified in families with Peutz-Jeghers syndrome. The identifications of germline mutations in families with Peutz-Jeghers syndrome could be a turning point in the management of Peutz-Jeghers syndrome.

Female↗
PubMed1999

Noise level of drilling instruments during mastoidectomy.

Exposure to intense noise has been identified as a potential risk in the development of hearing impairment. Social concern about excessive noise is increasing and this also extends to the operating room. A noise level study was performed in the operating room during mastoidectomy with a sound level meter and it was analyzed by a sound-analyzing program. The drilling instruments used included the Stryker, Midas, M.P.S. and Med-Next. The operator was exposed to sound levels from 69 to 83 dBA. The loudest drilling instrument was the Midas and it produced an average sound level of 83 dBA to the operator. The mean exposure time was 41 minutes during mastoidectomy. This is below the occupational noise-level regulations in Korea. However, considering that individual susceptibility to noise varies and that the otologic surgeon is repeatedly exposed to prolonged drilling noise, ear protection is recommended for the operators of high-speed drilling instruments.

Chronic Disease↗
PubMed1998

Differential modulation of transcriptional activity of oestrogen receptors by direct protein-protein interactions with retinoid receptors.

Control of oestradiol-responsive gene regulation by oestrogen receptors (ERs) may involve complex cross-talk with retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Recently, we have shown that ERalpha directly interacts with RARalpha and RXRalpha through their ligand binding domains (LBDs). In the present work, we extend these results by showing that ERbeta binds similarly to RARalpha and RXRalpha but not to the glucocorticoid receptor, as demonstrated by the yeast two-hybrid tests and glutathione S-transferase pull-down assays. These direct interactions were also demonstrated in gel-shift assays, in which the oestrogen response element (ERE) binding by ERalpha was enhanced by the RXRalpha LBD but was abolished by the RARalpha LBD. In addition, we showed that RARalpha and RXRalpha bound the ERE as efficiently as ERalpha, suggesting that competition for DNA binding may affect the transactivation function of the ER. In transient transfection experiments, co-expression of RARalpha or RXRalpha, along with ERalpha or ERbeta, revealed differential modulation of the ERE-dependent transactivation, which was distinct from the results when each receptor alone was co-transfected. Importantly, when the LBD of RARalpha was co-expressed with ERalpha, transactivation of ERalpha on the ERE was repressed as efficiently as when wild-type RARalpha was co-expressed. Furthermore, liganded RARalpha or unliganded RXRalpha enhanced the ERalpha transactivation, suggesting the formation of transcriptionally active heterodimer complexes between the ER and retinoid receptors. Taken together, these results suggest that direct protein-protein interactions may play major roles in the determination of the biological consequences of cross-talk between ERs and RARalpha or RXRalpha.

Animals↗
PubMed1998

Bcl3, an IkappaB protein, as a novel transcription coactivator of the retinoid X receptor.

We have recently shown that the IkappaB protein IkappaBbeta interacted with the retinoid X receptor (RXR) and inhibited the 9-cis-retinoic acid (RA)-dependent transactivations (Na, S.-Y., Kim, H.-J., Lee, S.-K., Choi, H.-S., Na, D. S., Lee, M.-O., Chung, M., Moore, D. D., and Lee, J. W. (1998) J. Biol. Chem. 6, 3212-3215). Herein, we show that a distinct IkappaB protein Bcl3 also interacts with RXR, as shown in the yeast two-hybrid tests and glutathione S-transferase pull-down assays. The Bcl3 interaction involved two distinct subregions of RXR, i.e. constitutive interactions of the N-terminal ABC domains and 9-cis-RA-dependent interactions of the C-terminal DEF domains. In contrast to IkappaBbeta, Bcl3 did not interact with the AF2 domain of RXR. Bcl3 specifically interacted with the general transcription factors TFIIB, TBP, and TFIIA but not with TFIIEalpha in the GST pull-down assays. TBP and TFIIA, however, were not able to interact with IkappaBbeta. Accordingly, Bcl3 coactivated the 9-cis-RA-induced transactivations of RXR, in contrast to the inhibitory actions of IkappaBbeta. In addition, coexpression of SRC-1 but not p300 further stimulated the Bcl3-mediated enhancement of the 9-cis-RA-induced transactivations of RXR. These results suggest that distinct IkappaB proteins differentially modulate the 9-cis-RA-induced transactivations of RXR in vivo.

Alitretinoin↗
PubMed1998

Ionophores and receptors using cation-pi interactions: collarenes.

Cation-pi interactions are important forces in molecular recognition by biological receptors, enzyme catalysis, and crystal engineering. We have harnessed these interactions in designing molecular systems with circular arrangement of benzene units that are capable of acting as ionophores and models for biological receptors. [n]Collarenes are promising candidates with high selectivity for a specific cation, depending on n, because of their structural rigidity and well-defined cavity size. The interaction energies of [n]collarenes with cations have been evaluated by using ab initio calculations. The selectivity of these [n]collarenes in aqueous solution was revealed by using statistical perturbation theory in conjunction with Monte Carlo and molecular dynamics simulations. It has been observed that in [n]collarenes the ratio of the interaction energies of a cation with it and the cation with the basic building unit (benzene) can be correlated to its ion selectivity. We find that collarenes are excellent and efficient ionophores that bind cations through cation-pi interactions. [6]Collarene is found to be a selective host for Li+ and Mg2+, [8]collarene for K+ and Sr2+, and [10]collarene for Cs+ and Ba2+. This finding indicates that [10]collarene and [8]collarene could be used for effective separation of highly radioactive isotopes, 137Cs and 90Sr, which are major constituents of nuclear wastes. More interestingly, collarenes of larger cavity size can be useful in capturing organic cations. [12]Collarene exhibits a pronounced affinity for tetramethylammonium cation and acetylcholine, which implies that it could serve as a model for acetylcholinestrase. Thus, collarenes can prove to be novel and effective ionophores/model-receptors capable of heralding a new direction in molecular recognition and host-guest chemistry.

Benzene Derivatives↗
PubMed1998

Androstane metabolites bind to and deactivate the nuclear receptor CAR-beta.

The orphan receptor CAR-beta binds DNA as a heterodimer with the retinoid-X receptor and activates gene transcription in a constitutive manner. Here we show that, in contrast to the classical nuclear receptors, the constitutive activity of CAR-beta results from a ligand-independent recruitment of transcriptional co-activators. While searching for potential ligands of CAR-beta, we found that the steroids androstanol and androstenol inhibit the constitutive activity of CAR-beta. This effect is stereospecific: only 3alpha-hydroxy, 5alpha-reduced androstanes are active. These androstanes do not interfere with heterodimerization or DNA binding of CAR-beta; instead, they promote co-activator release from the ligand-binding domain. These androstane ligands are examples of naturally occurring inverse agonists that reverse transcriptional activation by nuclear receptors. CAR-beta (constitutive androstane receptor-beta), therefore, defines an unanticipated steroidal signalling pathway that functions in a manner opposite to that of the conventional nuclear receptor pathways.

Androstanes↗