steroid binding
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Author(s):  
Jorge Morales-Montor ◽  
Álvaro Colin-Oviedo ◽  
Gloria María. González-González ◽  
José Prisco Palma-Nicolás ◽  
Alejandro Sánchez-González ◽  
...  

We explored the hypothesis that progesterone direct effect on Trichinella spiralis might be mediated indeed by a new steroid-binding parasite protein. Our first results showed that Progesterone decreases the parasite molting rate. We amplify, isolated, cloned and sequenced the PGRMC2 sequence using specific primers from known species. Furthermore, we expressed the protein and developed an antibody to performance immunofluorescent confocal microscopy, where detected that parasite cells showed expression of a P4-binding protein exclusively located at the oocyte and the parasite´s cuticle. Presence of the PGRMC2 protein in these cells was also confirmed by western blot and flow cytometry. Molecular modeling studies accompanied by computer docking using the sequenced protein showed that PGRMC2 is potentially able to bind steroid hormones such as progesterone, estradiol, testosterone, and dihydrodrotestosterone with different affinities. Phylogenetic analysis and sequence alignment clearly demonstrated that Trichinella spiralis PGRMC2 is related to a steroid-binding protein of another platyhelminths. Progesterone may probably act upon Trichinella spiralis oocytes probably by binding to PGRMC2. This research has implications in the field of host-parasite co-evolution as well as the sex-associated susceptibility to this infection. In a more practical matter, present results may contribute to the molecular design of new drugs with anti-parasite actions.


Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1464
Author(s):  
Christine Bone ◽  
E. James Squires

Androstenone circulates in the plasma bound to albumin before accumulating in the fat, resulting in the development of boar taint. Androstenone sulfate is more abundant in the circulation than free androstenone; however, it is unclear how androstenone sulfate is transported in the plasma and if steroid transport affects the development of boar taint. Therefore, the purpose of this study was to characterize the binding of androstenone sulfate in boar plasma and determine if variability in steroid binding affects the accumulation of androstenone in the fat. [3H]-androstenone sulfate was incubated with plasma and the steroid binding was quantified using gel filtration chromatography. Inter-animal variability was assessed by quantifying androstenone binding specificity in plasma obtained from boars that had high or low fat androstenone concentrations at slaughter. Androstenone sulfate bound minimally in the plasma and to isolated albumin, which suggests that it is transported primarily in solution. The specific binding of androstenone quantified in plasma and isolated albumin from low fat androstenone animals was significantly higher (p = 0.01) than in high fat androstenone boars. These results indicate that the binding of androstenone to albumin varies amongst individual animals and affects the transport of androstenone in the plasma and accumulation in the fat of the boar.


2021 ◽  
Vol 76 (1) ◽  
pp. 103-110
Author(s):  
Alexandra A. Povaliaeva ◽  
Ekaterina A. Pigarova ◽  
Anastasia A. Romanova ◽  
Larisa K. Dzeranova ◽  
Artem Y. Zhukov ◽  
...  

Vitamin D-binding protein (DBP) was discovered more than half a century ago as a polymorphic serum protein and is currently characterized by a variety of physiological properties. First of all, DBP carries the bulk of vitamin D metabolites circulating in the bloodstream, while albumin is the second most important transport protein, especially in patients with a low concentration of DBP in serum. Since it was discovered that only 12% of the total circulating DBP have occupied steroid binding sites, a vigorous study of other potential biological roles of DBP was initiated: actin utilization, regulation of inflammation and innate immunity mechanisms, fatty acid binding, effects on bone metabolism and participation in the tumor pathogenesis. This review focuses on the main known biological functions of DBP.


2020 ◽  
Vol 75 (6) ◽  
pp. 653-660
Author(s):  
O. V. Krusko ◽  
L. F. Sholokhov ◽  
L. V. Belenkaya ◽  
M. A. Rashidova ◽  
I. N. Danusevich ◽  
...  

Background. PCOS is one of the most common endocrinological pathologies in women of reproductive age, manifested by a wide range of clinical manifestations. There are many unresolved issues related to the pathogenesis, diagnosis and treatment of this pathological condition in different periods of reproductive age. Aim the objective of the study was to identify the features of the functioning of the pituitary-ovarian system in women with PCOS at different periods of reproductive age. Methods. Study was performed in 20172019 at the FSPSI SCFHHRP, and involved women aged 1845 years. The study groups included women (a group of women with PCOS and a control group) in the follicular phase from 1 to 12 days of the menstrual cycle. As a result of the survey, a group of 44 women with PCOS and a group of 56 healthy women were formed. PCOS was diagnosed according to ESHRE/ASRM criteria (Rotterdam, 2003). Next, subgroups of women in early reproductive age from 35 to 45 years were formed: a group of women with PCOS (n = 29) and a control group (n = 22). And groups of women in late reproductive age from 35 to 45 years were formed: a group of women with PCOS (n = 15) and a control group (n = 34). Conducted: questionnaire survey, general and gynecological examination, ultrasound examination of the pelvic organs, laboratory tests, statistical data analysis. Results. In women with polycystic ovary syndrome of early reproductive age (1835 years), we detected an increase in the level of testosterone by 2 times, DHEA-S by 1.3 times, 17-OH-progesterone by 2 times, sex steroid-binding globulin by 1.4 times, in comparison with control group. The ratio of luteinizing hormone to follicle-stimulating hormone increased by 52%. In women with polycystic ovary syndrome of late reproductive age (3545 years), we detected an increase in the level of testosterone by 1.5 times, 17-OH-progesterone by 1.9 times, luteinizing hormone by 1.4 times, sex steroid-binding globulin by 1.6 times, in comparison with control group, without any significant differences in DHEA-S. At the same time, the ratio of luteinizing hormone to follicle-stimulating hormone increased by 60%. Conclusion. The hormonal profile of women with PCOS of early and late reproductive period is characterized by series of age-related changes in the pituitary-ovarian system, which should be taken into account in preventive and therapeutic measures.


2020 ◽  
Author(s):  
Yoshinao Katsu ◽  
Islam MD Shari ◽  
Xiaozhi Lin ◽  
Wataru Takagi ◽  
Hiroshi Urushitani ◽  
...  

Abstract Orthologs of human glucocorticoid receptor (GR) and human mineralocorticoid receptor (MR) first appear in cartilaginous fishes. Subsequently, the MR and GR diverged to respond to different steroids: the MR to aldosterone and the GR to cortisol and corticosterone. We report that cortisol, corticosterone and aldosterone activate full-length elephant shark GR, and progesterone, which activates elephant shark MR, does not activate elephant shark GR. However, progesterone inhibits steroid binding to elephant shark GR, but not to human GR. Together, this indicates partial functional divergence of elephant shark GR from the MR. Deletion of the N-terminal domain (NTD) from elephant shark GR (truncated GR) reduced the response to corticosteroids, while truncated and full-length elephant shark MR had similar responses to corticosteroids. Swapping of NTDs of elephant shark GR and MR yielded an elephant shark MR chimera with full-length GR-like increased activation by corticosteroids and progesterone compared to full-length elephant shark MR. Elephant shark MR NTD fused to GR DBD+LBD had similar activation as full-length MR, indicating that the MR NTD lacked GR-like NTD activity. We propose that NTD activation of human GR evolved early in GR divergence from the MR.


2020 ◽  
Vol 295 (33) ◽  
pp. 11495-11512 ◽  
Author(s):  
Selwyn S. Jayakar ◽  
David C. Chiara ◽  
Xiaojuan Zhou ◽  
Bo Wu ◽  
Karol S. Bruzik ◽  
...  

Allopregnanolone (3α5α-P), pregnanolone, and their synthetic derivatives are potent positive allosteric modulators (PAMs) of GABAA receptors (GABAARs) with in vivo anesthetic, anxiolytic, and anti-convulsant effects. Mutational analysis, photoaffinity labeling, and structural studies have provided evidence for intersubunit and intrasubunit steroid-binding sites in the GABAAR transmembrane domain, but revealed only little definition of their binding properties. Here, we identified steroid-binding sites in purified human α1β3 and α1β3γ2 GABAARs by photoaffinity labeling with [3H]21-[4-(3-(trifluoromethyl)-3H-diazirine-3-yl)benzoxy]allopregnanolone ([3H]21-pTFDBzox-AP), a potent GABAAR PAM. Protein microsequencing established 3α5α-P inhibitable photolabeling of amino acids near the cytoplasmic end of the β subunit M4 (β3Pro-415, β3Leu-417, and β3Thr-418) and M3 (β3Arg-309) helices located at the base of a pocket in the β+–α− subunit interface that extends to the level of αGln-242, a steroid sensitivity determinant in the αM1 helix. Competition photolabeling established that this site binds with high affinity a structurally diverse group of 3α-OH steroids that act as anesthetics, anti-epileptics, and anti-depressants. The presence of a 3α-OH was crucial: 3-acetylated, 3-deoxy, and 3-oxo analogs of 3α5α-P, as well as 3β-OH analogs that are GABAAR antagonists, bound with at least 1000-fold lower affinity than 3α5α-P. Similarly, for GABAAR PAMs with the C-20 carbonyl of 3α5α-P or pregnanolone reduced to a hydroxyl, binding affinity is reduced by 1,000-fold, whereas binding is retained after deoxygenation at the C-20 position. These results provide a first insight into the structure-activity relationship at the GABAAR β+–α− subunit interface steroid-binding site and identify several steroid PAMs that act via other sites.


2020 ◽  
Author(s):  
Jian Wu ◽  
Simon Michaeli ◽  
Gad Galili ◽  
Hadas Peled-Zehavi

AbstractER-phagy, the selective autophagy of endoplasmic reticulum (ER) components, is known to operate in eukaryotes from yeast and unicellular algae to animals and plants. Thus far, only ER-stress derived ER-phagy was reported and analyzed in plants. In this study we characterize an ER-phagy pathway in Arabidopsis thaliana that is triggered by dark-induced starvation and not by ER-stress. This pathway is defined by the previously reported ATG8-interacting proteins, ATI1 and ATI2 and is regulated by the TOR signaling pathway. We further identified ER-localized Membrane Steroid Binding Protein 1 (MSBP1) as an ATI1 and 2 interacting protein and an autophagy cargo, and show that ATI1 and 2 serve as its cargo receptors. Together, these findings expand our knowledge on plants responses during energy deprivation and highlight the role of this special type of ER-phagy in this process.


2019 ◽  
Author(s):  
Yoshinao Katsu ◽  
Islam MD Shariful ◽  
Xiaozhi Lin ◽  
Wataru Takagi ◽  
Hiroshi Urushitani ◽  
...  

AbstractOrthologs of human glucocorticoid receptor (GR) and human mineralocorticoid receptor (MR) first appear in cartilaginous fishes. Subsequently, the MR and GR diverged to respond to different steroids: the MR to aldosterone and the GR to cortisol and corticosterone. We report that cortisol, corticosterone and aldosterone activate full-length elephant shark GR, and progesterone, which activates elephant shark MR, does not activate elephant shark GR. However, progesterone inhibits steroid binding to elephant shark GR, but not to human GR. Together, this indicates partial functional divergence of elephant shark GR from the MR. Deletion of the N-terminal domain (NTD) from elephant shark GR (truncated GR) reduced the response to corticosteroids, while truncated and full-length elephant shark MR had similar responses to corticosteroids. Swapping of NTDs of elephant shark GR and MR yielded an elephant shark MR chimera with full-length GR-like increased activation by corticosteroids and progesterone compared to full-length elephant shark MR. Elephant shark MR NTD fused to GR DBD+LBD had similar activation as full-length MR, indicating that the MR NTD lacked GR-like NTD activity. We propose that NTD activation of human GR evolved early in GR divergence from the MR.


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