scholarly journals Regulation by Progestins, Corticosteroids and RU486 of Activation of Elephant Shark and Human Progesterone Receptors: An Evolutionary Perspective

2021 ◽  
Author(s):  
Xiaozhi Lin ◽  
Wataru Takagi ◽  
Susumu Hyodo ◽  
Shigeho Ijiri ◽  
Yoshinao Katsu ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Progesterone Receptors ◽  
Cartilaginous Fish ◽  
Evolutionary Perspective ◽  
Elephant Shark ◽  
Hydroxy Progesterone

AbstractWe investigated progestin and corticosteroid activation of the progesterone receptor (PR) from elephant shark (Callorhinchus milii), a cartilaginous fish belonging to the oldest group of jawed vertebrates. Comparison with human PR experiments provides insights into the evolution of steroid activation of human PR. At 1 nM steroid, elephant shark PR is activated by progesterone, 17-hydroxy-progesterone, 20β-hydroxy-progesterone, 11-deoxycorticosterone (21-hydroxyprogesterone) and 11-deoxycortisol. At 1 nM steroid, human PR is activated only by progesterone and11-deoxycorticosterone indicating increased specificity for progestins and corticosteroids during the evolution of human PR. RU486, an important clinical antagonist of human PR, did not inhibit progesterone activation of elephant shark PR. Cys-528 in elephant shark PR corresponds to Gly-722 in human PR, which is essential for RU486 inhibition of human PR. Confirming the importance of this site on elephant shark PR, RU486 inhibited progesterone activation of the Cys528Gly mutant PR. There also was a decline in activation of elephant shark Cys528Gly PR by 11-deoxycortisol, 17-hydroxy-progesterone and 20β-hydroxy-progesterone and an increase in activation of human Gly722Cys PR by 11-deoxycortisol and decreased activation by corticosterone. One or more of these changes may have selected for the mutation corresponding to human glycine-722 PR that first evolved in platypus PR, a basal mammal.

scholarly journals Regulation by Progestins, Corticosteroids and RU486 of Activation of Elephant Shark and Human Progesterone Receptors: An Evolutionary Perspective

2021 ◽  
Author(s):  
Xiaozhi Lin ◽  
Wataru Takagi ◽  
Susumu Hyodo ◽  
Shigeho Ijiri ◽  
Yoshinao Katsu ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Progesterone Receptors ◽  
Cartilaginous Fish ◽  
Evolutionary Perspective ◽  
Elephant Shark ◽  
Hydroxy Progesterone

Abstract We investigated progestin and corticosteroid activation of the progesterone receptor (PR) from elephant shark (Callorhinchus milii), a cartilaginous fish belonging to the oldest group of jawed vertebrates. Comparison with human PR experiments provides insights into the evolution of steroid activation of human PR. At 1 nM steroid, elephant shark PR is activated by progesterone, 17-hydroxy-progesterone, 20b-hydroxy-progesterone, 11-deoxycorticosterone (21-hydroxyprogesterone) and 11-deoxycortisol. At 1 nM steroid, human PR is activated only by progesterone and11-deoxycorticosterone indicating increased specificity for progestins and corticosteroids during the evolution of human PR. RU486, an important clinical antagonist of human PR, did not inhibit progesterone activation of elephant shark PR. Cys-528 in elephant shark PR corresponds to Gly-722 in human PR, which is essential for RU486 inhibition of human PR. Confirming the importance of this site on elephant shark PR, RU486 inhibited progesterone activation of the Cys528Gly mutant PR. There also was a decline in activation of elephant shark Cys528Gly PR by 11-deoxycortisol, 17-hydroxy-progesterone and 20b-hydroxy-progesterone and an increase in activation of human Gly722Cys PR by 11-deoxycortisol and decreased activation by corticosterone. One or more of these changes may have selected for the mutation corresponding to human glycine-722 PR that first evolved in platypus PR, a basal mammal.

An immunohistochemical study of estrogen and progesterone receptors in adenocarcinoma of the endometrium and in the adjacent mucosa

1995 ◽  
Vol 5 (4) ◽  
pp. 275-281 ◽  
Author(s):  
H. Kerner ◽  
E. Sabo ◽  
M. Friedman ◽  
D. Beck ◽  
O. Samare ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Endometrial Cancer ◽  
Progesterone Receptor ◽  
Estrogen Receptor Status ◽  
Endometrial Adenocarcinoma ◽  
Progesterone Receptors ◽  
Myometrial Invasion ◽  
Inverse Correlation ◽  
Immunohistochemical Analysis ◽  
Receptor Status

The immunoperoxidase stain for estrogen and progesterone receptor content in endometrial adenocarcinoma was correlated with the grade and stage, level of myometrial invasion, age and survival of the patients. Anti-estrogen and anti-progesteone receptor monoclonal antibodies were applied to paraffin-embedded tissue from hysterectomy specimens of 100 patients with adenocarcinoma of the endometrium. In 34 of the cases the receptors were studied in the endometrium adjacent to the tumor and compared to the nuclear receptor content in the carcinoma. There was a high inverse correlation between the estrogen receptor status and the grade of tumor (R= − 0.45,P= 0.006). The estrogen receptor measured in the endometrium near the tumor showed a negative correlation with the grade of the tumor (R= −0.42,P= 0.013). The estrogen, but not the progesterone, receptor content, was positively related to the age of the patient (P< 0.05). No significant correlation of the receptor status with the depth of myometrial invasion was found, despite the obvious interdependence between the grade and myometrial invasion. The progesterone receptor staining index appeared to be a distinct independent prognostic factor in endometrial cancer. The immunohistochemical analysis of the steroid hormone status in endometrial cancer therefore offers an alternative to the quantitative ligand-binding assay.

scholarly journals The Expression of Progesterone Receptors in Meningiomas of Different Grades

2019 ◽  
Vol 8 (2) ◽  
pp. 65-69
Author(s):  
Mohammad Tahir ◽  
Tehreem Atif ◽  
Summaya Sohail ◽  
Arfa Nawazish ◽  
Huma Mushtaq
Keyword(s):  
Progesterone Receptor ◽  
Treatment Options ◽  
Progesterone Receptors ◽  
Lower Grade ◽  
Immunoperoxidase Method ◽  
Nuclear Staining ◽  
Who Grade ◽  
Grade Ii ◽  
Who Grade Iii ◽  
Grade Iii

Background: Meningiomas are slow growing intracranial and intraspinal neoplasms with a tendency to recur locally. WHO grades them as I (benign), II (atypical) and III (anaplastic) in order of their increasing aggressiveness, based on histological parameters and brain parenchymal invasion. Progesterone receptors (PR) are more prevalent amongst the lower grade meningiomas. The objective of this study was to determine the immunohistochemical expression of progesterone receptors in meningiomas of different grades.Material and Methods: A total of 100 cases were selected over a period of 2.5 years. Three to five microns’ thick sections stained with Hematoxylin and Eosin were examined microscopically by a team of two Histopathologists and graded into grades I, II and III, according to 2016 WHO classification criteria. Another section of the original tumor was stained with progesterone receptor antibody using the conventional immunoperoxidase method. Stained slides were than examined by the same team of Histopathologists and declared positive (if nuclear staining was observed in more than 10% of tumor cells) or negative. Statistical analysis was done using SPSS version 21.Results: Out of a total of 100 cases of meningioma, there were 79 cases of benign/typical WHO grade I, 15 cases of atypical/ WHO grade II and 6 cases of anaplastic/ WHO grade III tumor. PR status was positive in 89.8 % (71/79) of grade I meningiomas and 46.6 % (7/15) of grade II/Atypical meningiomas. The 06 cases of Anaplastic/WHO grade III tumors were negative for PR. There was a higher prevalence of Progesterone receptors in female patients (89.8%; 53/59) as compared to male meningioma patients (60.9%; 25/41).Conclusion: We observed a decreased expression of progesterone receptor in higher grades of meningioma in this study. It is an effort to explore conservative treatment options for inoperable lesions, as anti-progesterone therapy may hold a promise as a new treatment option in the near future.

scholarly journals Methamphetamine Administration Increases Proceptive Behavior by Activating Src Kinase and Upregulating Progesterone Receptor in the Medial Amygdala

2018 ◽  
Author(s):  
Katrina M Williams ◽  
Sarah A Rudzinskas ◽  
Jessica A Mong
Keyword(s):  
Progesterone Receptor ◽  
Phosphorylation Site ◽  
Progesterone Receptors ◽  
Receptor Expression ◽  
Medial Amygdala ◽  
Specific Manner ◽  
Receptor Action ◽  
Necessary And Sufficient ◽  
Motivated Behaviors

Methamphetamine, a psychostimulant drug of abuse, increases sexual motivation both in humans and in rodent models. The activation of dopamine type-1 receptors (D1Rs) within the medial amygdala, in the presence of ovarian hormones (EB+P), are both necessary and sufficient for increases in proceptive, or sexually motivated, behaviors. Here, we demonstrate that methamphetamine increases progesterone receptor expression in the medial amygdala independently of D1R activation, and that lentiviral overexpression of the progesterone receptor was able to recapitulate the methamphetamine-induced enhancement of proceptive behaviors. Furthermore, we found that within the medial amygdala, these progesterone receptors show an increase in phosphorylation of serine 294 of the progesterone receptor in a region-specific manner. The involvement of this phosphorylation site suggests a role for cytosolic kinases, which may be responsible for enhanced progesterone receptor action. The phosphorylation of serine 294 is blocked by D1R antagonists, and by inhibiting cSrc and ERK1/2, downstream of D1R signaling, we identified that Src and ERK1/2 are required for enhanced proceptive behavior. Taken together, we propose that within the medial amygdala, methamphetamine enhances progesterone receptors sensitivity to its cognate ligand via interaction with cSrc kinase and ERK1/2, as well as an increase total progesterone receptors, thus leading to enhanced proceptive behaviors in the rat.

scholarly journals Non-genomic progesterone receptors in the mammalian ovary: some unresolved issues

Reproduction ◽  
2003 ◽  
pp. 3-15 ◽  
Author(s):  
T Bramley
Keyword(s):  
Progesterone Receptor ◽  
Steroid Receptors ◽  
Surface Membrane ◽  
Progesterone Receptors ◽  
Signalling Pathways ◽  
Mediated Effects ◽  
Genomic Effects ◽  
Vitamin D 3 ◽  
Membrane Progesterone Receptor ◽  
Different Tissues

In addition to their well-documented genomic effects, steroid hormones may also exert actions that are: (i) rapid, (ii) insensitive to inhibitors of transcription, (iii) mimicked by steroids coupled to cell membrane-impermeant molecules, and (iv) demonstrable in cells that do not express the classic genomic progesterone receptor (gPR). Such 'non-genomic' effects have been described for all the major classes of steroids (progesterone, oestrogens, androgens and corticoids), as well as for thyroid hormones, retinoids and vitamin D(3). Rapid, membrane-mediated effects of progesterone have been studied most intensively in human spermatozoa and in the Xenopus oocyte. However, similar non-genomic actions of progesterone and other steroids have now been described in a wide variety of different tissues in many species. The first putative membrane steroid receptor to be cloned was that for the pig membrane progesterone receptor (mPR). Subsequently, similar genes were cloned from rats and cattle, and two related mPRs have been described in humans. Despite accumulating evidence for cell-surface membrane actions of steroids, a number of uncertainties remain as to the properties and identity of such 'receptors' and their cellular actions. Furthermore, some rapid steroid effects may be mediated through membrane-associated 'classical' steroid receptors, and steroid receptors may be capable of activating other signalling pathways non-classically. This review focuses on some of these unresolved issues, taking as its model the actions of progesterone in the mammalian ovary.

COMPARISON OF THE CHARACTERISTICS AND OF THE HORMONAL CONTROL OF ENDOMETRIAL AND MYOMETRIAL PROGESTERONE RECEPTORS

1975 ◽  
Vol 66 (3) ◽  
pp. 349-356 ◽  
Author(s):  
M. T. LUU THI ◽  
E. E. BAULIEU ◽  
E. MILGROM
Keyword(s):  
Progesterone Receptor ◽  
Guinea Pig ◽  
Binding Sites ◽  
Guinea Pigs ◽  
Progesterone Receptors ◽  
Relative Increase ◽  
Hormonal Control ◽  
Diploid Genome ◽  
The Absolute ◽  
Hormone Specificity

SUMMARY The characteristics of endometrial and myometrial progesterone receptor of guinea-pig were compared. Affinity for progesterone, hormone specificity, sedimentation properties (in oestrogen-primed animals), inhibition of binding by p-hydroxymercuribenzoate were found to be identical in both tissues. Differences were, however, observed in the hormonal control of the concentration of receptor. In all the situations studied, the concentration of receptors was higher in the endometrium than in the myometrium. In guinea-pigs ovariectomized at dioestrus the concentration was 3500 binding sites per diploid genome in the myometrium and 20300 in the endometrium; 1–3 days after oestradiol injection, this concentration was raised to 46000–38000 and 65000–83000 binding sites respectively. Thus the absolute rise was similar in both tissues but the relative increase was about 15-fold in the myometrium and only three- to fourfold in the endometrium. After injection of 2 mg progesterone, the concentration of receptor previously induced by oestrogen returned to very low values similar to those observed in non-hormonally treated controls. This difference between endometrial and myometrial receptors could be due either to a faster turnover of the latter or to the existence of a stable non-hormonally controlled population of receptors, present only in the endometrium.

scholarly journals Parathyroid hormone gene family in a cartilaginous fish, the elephant shark (Callorhinchus milii)

2010 ◽  
Vol 25 (12) ◽  
pp. 2613-2623 ◽  
Author(s):  
Yang Liu ◽  
Alexander S Ibrahim ◽  
Boon-Hui Tay ◽  
Samantha J Richardson ◽  
Justin Bell ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Gene Family ◽  
Cartilaginous Fish ◽  
Elephant Shark
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