scholarly journals In Vitro Evidence Suggests Activin-A May Promote Tissue Remodeling Associated with Human Luteolysis

Endocrinology ◽  
2007 ◽  
Vol 148 (8) ◽  
pp. 3730-3739 ◽  
Author(s):  
Michelle Myers ◽  
Eva Gay ◽  
Alan S. McNeilly ◽  
Hamish M. Fraser ◽  
W. Colin Duncan
Keyword(s):  
Granulosa Cells ◽  
Primary Cultures ◽  
Gelatin Zymography ◽  
Activin A ◽  
Primary Cell ◽  
Matrix Metalloproteinase 2 ◽  
Corpora Lutea ◽  
Type I ◽  
Rt Pcr ◽  
Maternal Recognition Of Pregnancy

Luteolysis in women is associated with an up-regulation of the expression and activity of matrix metalloproteinase-2 (MMP-2), which is inhibited by human chorionic gonadotropin (hCG) during maternal recognition of pregnancy. Because the primary source of MMP-2 is fibroblasts that do not express LH/hCG receptors, we aimed to investigate the regulation of MMP-2. Women with regular cycles having hysterectomy for nonmalignant conditions and women undergoing oocyte retrieval for assisted conception were used in this current study. Novel primary cultures and cocultures of luteinized granulosa cells and fibroblast-like cells in conjunction with human corpora lutea from different stages of the luteal phase were used to investigate the role of activin-A in the corpus luteum. The effect of hCG, activin-A, and follistatin on MMP-2 activity and expression was assessed by gelatin zymography and quantitative RT-PCR in primary cell cultures. Confirmation of signaling pathways involved in the activation of MMP-2 was assessed by immunofluorescence, RT-PCR, and quantitative RT-PCR. In primary cell culture, steroidogenic cells secrete activin-A and its inhibitors, inhibin-A and follistatin. Follistatin expression is up-regulated by hCG (P < 0.05). The fibroblast-like cells producing MMP-2 have the machinery for activin reception, expressing both type I and type II activin receptors and Smad proteins. Activin-A up-regulated both activity and expression of MMP-2 in fibroblast-like cells (P < 0.05). This activity was inhibited in cocultures of luteinized granulosa cells and fibroblast-like cells in the presence of hCG (P < 0.05) or follistatin (P < 0.01). Activin-A is an excellent candidate for an effector molecule in human luteolysis whose paracrine action is inhibited during maternal recognition of pregnancy.

scholarly journals Gene expression and protein localisation for activin-A, follistatin and activin receptors in goat ovaries

2004 ◽  
Vol 183 (2) ◽  
pp. 405-415 ◽  
Author(s):  
J R V Silva ◽  
R van den Hurk ◽  
H T A van Tol ◽  
B A J Roelen ◽  
J R Figueiredo
Keyword(s):  
Mrna Expression ◽  
Granulosa Cells ◽  
Activin A ◽  
Surface Epithelium ◽  
Corpora Lutea ◽  
Rt Pcr ◽  
Primordial Follicles ◽  
Antral Follicles ◽  
Theca Cells ◽  
Activin Receptors

We studied the protein and mRNA expression of activin-A, follistatin and activin receptors in goat ovaries to find evidence of their possible role in ovarian activity, particularly in the various stages of follicle development. Ovaries of cyclic goats were collected and then either fixed in paraformaldehyde for immunohistochemical localisation of activin-A, follistatin, activin receptors IIA/B (ActR-IIA/B) and IA (ActR-IA) proteins or used to obtain samples to demonstrate mRNA expression of activin-A (βA subunit), follistatin, ActR-IIA, -IIB, -IA and -IB, using RT-PCR. For this latter goal, primordial, primary and secondary follicles were isolated mechanically, washed to remove the stromal cells and then used for RT-PCR. In addition, oocytes, cumulus, mural granulosa and theca cells from small (<3 mm) and large (3–6 mm) antral follicles, luteal cells and surface epithelium were collected to study mRNA expression. Activin-A and follistatin proteins were found in oocytes of all follicle classes, granulosa cells from the primary follicle stage onwards, theca cells of antral follicles, corpora lutea and ovarian surface epithelium. In antral follicles, these proteins were detected both in cumulus and mural granulosa cells. ActR-IIA/B protein was found at the same follicular sites, and also in granulosa cells of primordial follicles onward. The localisation of ActR-IA corresponded with that of ActR-IIA/B, but the former protein was absent in the theca of large antral follicles. The mRNAs for activin-A (βA subunit), follistatin, and ActR-IIA, -IIB, -IA and -IB were detected at all follicular and cellular types studied, except that ActR-IIB was not found in follicles that had not developed an antrum yet. In conclusion, in goat ovaries, transcripts of activin-A (βA subunit), its receptors and its binding protein follistatin are expressed and their proteins formed at all follicular stages and in corpora lutea. These findings indicate a role of activin-A in the local regulatory system during the entire follicular development and during luteal activity.

scholarly journals Detection of SARS-COV-2 receptor ACE-2 mRNA in thyroid cells: a clue for COVID-19-related subacute thyroiditis

2020 ◽  
Author(s):  
M. Rotondi ◽  
F. Coperchini ◽  
G. Ricci ◽  
M. Denegri ◽  
L. Croce ◽  
...  
Keyword(s):  
Primary Cultures ◽  
Thyroid Tissue ◽  
Subacute Thyroiditis ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Type I ◽  
Rt Pcr ◽  
Follicular Cells ◽  
Thyroid Cells ◽  
Tissue Samples

Abstract Purpose SARS-COV-2 is a pathogenic agent belonging to the coronavirus family, responsible for the current global world pandemic. Angiotensin-converting enzyme 2 (ACE-2) is the receptor for cellular entry of SARS-CoV-2. ACE-2 is a type I transmembrane metallo-carboxypeptidase involved in the Renin-Angiotensin pathway. By analyzing two independent databases, ACE-2 was identified in several human tissues including the thyroid. Although some cases of COVID-19-related subacute thyroiditis were recently described, direct proof for the expression of the ACE-2 mRNA in thyroid cells is still lacking. Aim of the present study was to investigate by RT-PCR whether the mRNA encoding for ACE-2 is present in human thyroid cells. Methods RT-PCR was performed on in vitro ex vivo study on thyroid tissue samples (15 patients undergoing thyroidectomy for benign thyroid nodules) and primary thyroid cell cultures. Results The ACE-2 mRNA was detected in all surgical thyroid tissue samples (n = 15). Compared with two reporter genes (GAPDH: 0.052 ± 0.0026 Cycles−1; β-actin: 0.044 ± 0.0025 Cycles−1; ACE-2: 0.035 ± 0.0024 Cycles−1), the mean level of transcript expression for ACE-2 mRNA was abundant. The expression of ACE-2 mRNA in follicular cells was confirmed by analyzing primary cultures of thyroid cells, which expressed the ACE-2 mRNA at levels similar to tissues. Conclusions The results of the present study demonstrate that the mRNA encoding for the ACE-2 receptor is expressed in thyroid follicular cells, making them a potential target for SARS-COV-2 entry. Future clinical studies in patients with COVID-19 will be required for increase our understanding of the thyroid repercussions of SARS-CoV-2 infection.

scholarly journals Bone morphogenetic protein (BMP) ligands and receptors in bovine ovarian follicle cells: actions of BMP-4, -6 and -7 on granulosa cells and differential modulation of Smad-1 phosphorylation by follistatin

Reproduction ◽  
2004 ◽  
Vol 127 (2) ◽  
pp. 239-254 ◽  
Author(s):  
Claire Glister ◽  
C Fred Kemp ◽  
Philip G Knight
Keyword(s):  
Granulosa Cells ◽  
Ovarian Follicle ◽  
Viable Cell ◽  
Receptor Activation ◽  
Cell Number ◽  
Activin A ◽  
Follicle Cells ◽  
Viable Cell Number ◽  
Type I ◽  
Antral Follicles

Given the paucity of information on the potential roles of bone morphogenetic proteins (BMPs) in the ruminant ovary we conducted immunolocalization and functional studies on cells isolated from bovine antral follicles. Immunocytochemistry revealed expression of BMP-4 and -7 in isolated theca cells whereas granulosa cells and oocytes selectively expressed BMP-6. All three cell types expressed a range of BMP-responsive type-I (BMPRIB, ActRI) and type-II (BMPRII, ActRII, ActRIIB) receptors supporting autocrine/paracrine roles within the follicle. This was reinforced by functional experiments on granulosa cells which showed that BMP-4, -6 and -7 promoted cellular accumulation of phosphorylated Smad-1 but not Smad-2 and enhanced ‘basal’ and IGF-stimulated secretion of oestradiol (E2), inhibin-A, activin-A and follistatin (FS). Concomitantly, each BMP suppressed ‘basal’ and IGF-stimulated progesterone secretion, consistent with an action to prevent or delay atresia and/or luteinization. BMPs also increased viable cell number under ‘basal’ (BMP-4 and -7) and IGF-stimulated (BMP-4, -6 and -7) conditions. Since FS, a product of bovine granulosa cells, has been shown to bind several BMPs, we used the Biacore technique to compare its binding affinities for activin-A (prototype FS ligand) and BMP-4, -6 and -7. Compared with activin-A (Kd 0.28 ± 0.02 nM; 100%), the relative affinities of FS for BMP-4, -6 and -7 were 10, 5 and 1% respectively. Moreover, studies on granulosa cells showed that preincubation of ligand with excess FS abolished activin-A-induced phosphorylation of Smad-2 and BMP-4-induced phosphorylation of Smad-1. However, FS only partially reversed BMP-6-induced Smad-1 phosphorylation and had no inhibitory effect on BMP-7-induced Smad-1 phosphorylation. These findings support functional roles for BMP-4, -6 and -7 as paracrine/autocrine modulators of granulosa cell steroidogenesis, peptide secretion and proliferation in bovine antral follicles. The finding that FS can differentially modulate BMP-induced receptor activation and that this correlates with the relative binding affinity of FS for each BMP type implicates FS as a potential modulator of BMP action in the ovary.

scholarly journals Activins regulate 17β-hydroxysteroid dehydrogenase type I transcription in murine gonadotrope cells

2009 ◽  
Vol 201 (1) ◽  
pp. 89-104 ◽  
Author(s):  
Beata Bak ◽  
Laura Carpio ◽  
Jinjing L Kipp ◽  
Pankaj Lamba ◽  
Ying Wang ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Intracellular Signaling ◽  
Cell Types ◽  
Hydroxysteroid Dehydrogenase ◽  
Activin A ◽  
Type I ◽  
Promoter Regions ◽  
Gene Encoding ◽  
17Β Estradiol ◽  
Smad Binding Element

Activins are pleiotropic members of the TGFβ superfamily and were initially characterized based on their abilities to stimulate FSH synthesis and secretion by gonadotrope cells of the anterior pituitary gland. Here, we identified the gene encoding the steroidogenic enzyme, 17β-hydroxysteroid dehydrogenase type I (17β-HSD1; Hsd17b1), as an activin-responsive gene in immortalized gonadotrope cells, LβT2. 17β-HSD1 catalyzes the conversion of estrone to the more active 17β-estradiol, and activin A stimulated an increase in this enzymatic activity in these cells. We demonstrated that activins signaled via the type I receptor, activin receptor-like kinase (ALK4), and the intracellular signaling protein, SMAD2, to regulate Hsd17b1 transcription in immediate-early fashion. Critical cis-elements, including a minimal SMAD-binding element, were mapped to within 100 bp of the start of transcription. Activin/ALK4 signaling also regulated Hsd17b1 transcription in both immortalized and primary cultured murine granulosa cells. The promoter regions mediating basal and activin/ALK4-regulated promoter activity were generally conserved across the different cell types. The data show that activin A rapidly regulates Hsd17b1 transcription in gonadotrope and granulosa cells and may thereby regulate local 17β-estradiol synthesis.

scholarly journals Expression of activin A and its receptors in human pheochromocytomas

2000 ◽  
Vol 165 (2) ◽  
pp. 503-508 ◽  
Author(s):  
J Liu ◽  
P Heikkila ◽  
AI Kahri ◽  
R Voutilainen
Keyword(s):  
Protein Kinase ◽  
Mrna Expression ◽  
Kinase Inhibitor ◽  
Receptor Gene ◽  
Primary Cultures ◽  
Activin A ◽  
Enzyme Linked Immunosorbent Assay ◽  
Type I ◽  
Pheochromocytoma Cells

Activin A (a homodimer of two activin betaA subunits) has been shown to induce the neuronal differentiation of rat pheochromocytoma PC12 cells. We studied activin A and its receptor gene expression in human pheochromocytomas in vivo and in vitro to clarify the potential involvement of activin A in the pathophysiology of these tumors. We first screened 20 pheochromocytomas and nine normal adrenal tissues for activin betaA mRNA expression. Northern blots hybridized with specific oligonucleotide probes detected weak signals for activin betaA transcripts in pheochromocytomas. Both type I and type II activin receptor (ActR-I, ActR-IB and ActR-II) mRNA expression was also detectable in the pheochromocytoma tissues. In primary cultures of pheochromocytoma cells, expression of activin betaA mRNA was readily detectable by Northern blotting, and secretion of activin A into the conditioned medium was confirmed by an enzyme-linked immunosorbent assay. The expression of activin betaA mRNA and secretion of activin A were induced by (Bu)(2)cAMP after 1 and 3 days of treatment (all P<0.05). A protein kinase inhibitor, staurosporine, inhibited the basal and (Bu)(2)cAMP-induced accumulation of activin betaA mRNA (P<0.05). In addition, induction of chromaffin phenotype by dexamethasone also inhibited the basal and (Bu)(2)cAMP-induced expression of activin A at both mRNA and protein levels (all P<0.05). In contrast, the expression of ActR-I and ActR-IB mRNAs was not affected by these agents in cultured pheochromocytoma cells. In summary, activin betaA subunit and activin receptors are expressed in human pheochromocytomas. Production of activin A in cultured pheochromocytoma cells is induced through the protein kinase A pathway, but reduced during chromaffin differentiation. Therefore, activin A may function as a local neurotrophic factor via an auto/paracrine manner in human pheochromocytomas.

scholarly journals Pituitary adenylate cyclase-activating polypeptide acts synergistically with relaxin in modulating ovarian cell function in rats

2000 ◽  
Vol 167 (1) ◽  
pp. 61-69 ◽  
Author(s):  
CH Teng ◽  
FC Ke ◽  
MT Lee ◽  
SW Lin ◽  
L Chen ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Gelatin Zymography ◽  
Interstitial Cells ◽  
Camp Signaling ◽  
Matrix Metalloproteinase 2 ◽  
Ovarian Cells ◽  
Camp Signaling Pathway ◽  
Pituitary Adenylate Cyclase

The interactive effects of pituitary adenylate cyclase-activating polypeptide (PACAP) and relaxin on the secretion of gelatinases, involved in matrix remodeling, in ovarian theca-interstitial cells and granulosa cells, were investigated in gonadotropin-primed immature rats. The gelatinases secreted from cultured cells were analyzed using gelatin zymography and scanning densitometry. We have previously shown that relaxin stimulated the secretion of a 71 kDa gelatinase, identified as a type IV collagenase (matrix metalloproteinase 2), in rat theca-interstitial cells. This study has demonstrated that PACAP27 and PACAP38, with similar potency, dose-dependently enhanced relaxin-induced secretion of 71 kDa gelatinase, whereas PACAP alone had no effect. In rat granulosa cells, both PACAP27 and PACAP38 alone dose-dependently increased the secretion of a 63 kDa gelatinase. In addition, this study has shown that cAMP signaling pathway mediators act similarly to that of PACAP on gelatinase secretion in rat ovarian cells. Cholera toxin, forskolin and 8-bromoadenosine cAMP augmented relaxin-induced secretion of 71 kDa gelatinase in theca-interstitial cells, and alone they had no effect. These mediators also increased the secretion of 63 kDa gelatinase in granulosa cells. It is well known that the increase in cellular cAMP level is associated with the morphological rounding-up phenomenon in granulosa cells. This study has shown that PACAP and cAMP pathway mediators, but not relaxin, could cause such changes in cell shape in granulosa cells as well as in theca-interstitial cells. In conclusion, this study provides original findings that PACAP acts synergistically with relaxin in stimulating the secretion of gelatinases in rat ovarian theca-interstitial cells and granulosa cells. This supports the idea that relaxin and PACAP may serve as ovarian physiological mediators of gonadotropin function in facilitating the ovulatory process. In addition, PACAP appears to act through the cAMP signaling pathway to affect biological functions in ovarian cells, whereas relaxin does not.

scholarly journals The localisation and expression of 5 alpha-reductase types I and II mRNAs in human hyperplastic prostate and in prostate primary cultures

1998 ◽  
Vol 156 (3) ◽  
pp. 509-517 ◽  
Author(s):  
FK Habib ◽  
M Ross ◽  
CW Bayne ◽  
K Grigor ◽  
AC Buck ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mrna Expression ◽  
Primary Cultures ◽  
Secretory Cells ◽  
Enzyme Assays ◽  
Type I ◽  
Rt Pcr ◽  
Stromal Component ◽  
Hyperplastic Tissue

The expression and localisation of mRNAs for 5 alpha reductase Type I (5 alpha R-I) and Type II (5 alpha R-II) isoenzymes in human benign prostatic hyperplasia (BPH) were investigated by RT-PCR and by in mini hybridisation (ISH) using digoxigenin labelled riboprobes. In addition, we also examined the isoenzymes mRNA expression in primary BPH cultures of separated stroma/fibroblast and epithelial cells to determine whether primary cultures are appropriate models in which to investigate 5 alpha R activity and regulation. The results demonstrated conclusively the presence of mRNA encoding both isoenzymes in all specimens so far examined. Additionally, the presence of a functional 5 alpha R-I and -II activity in BPH was confirmed by enzyme assays. ISH studies localised the mRNA expression to both the fibroblast/stromal component as well as the epithelial cells of the hyperplastic tissue. In the glandular regions the expression for both isoenzymes was particularly strong in the basal layers of the epithelium whereas mRNA expression in the secretory cells was less pronounced. Expression of 5 alpha R-I and -II mRNAs in fibroblast was on the other hand variable with high expression in some areas and little in others. These findings were supported by our primary culture experiments which demonstrated that both the fibroblast and epithelial cells maintain a capacity to express both isoenzymes in vitro. In the case of the fibroblast, the capacity to express the isoenzymes was maintained following the sequential passaging of the cells up to passage 6, after which the cells no longer expressed either isoenzyme.

scholarly journals The Value of Combined Use of Survivin mRNA and Matrix Metalloproteinase 2 and 9 for Bladder Cancer Detection in Voided Urine

2013 ◽  
Vol 34 (1) ◽  
pp. 57-62 ◽  
Author(s):  
Sanaa Eissa ◽  
Soheir Badr ◽  
Shadia Abd Elhamid ◽  
Azza Salah Helmy ◽  
Mohamed Nour ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Matrix Metalloproteinase ◽  
Urothelial Carcinoma ◽  
Gelatin Zymography ◽  
Urine Cytology ◽  
Matrix Metalloproteinase 2 ◽  
Rt Pcr ◽  
Diagnostic Efficacy ◽  
Cancer Early Detection ◽  
Combined Use

Objective: In a trial to improve the diagnostic efficacy of conventional urine cytology we determine survivin RNA and matrix metalloproteinase 2 and 9 in urine of bladder cancer cases.Method: Voided urine specimens were collected from patients with histologically confirmed bladder urothelial carcinoma (Group 1;n= 46), urological patients without urothelial carcinoma (Group 2;n= 20), and healthy volunteers (Group 3;n= 20). Urine cytology, survivin RNA was estimated by qualitative nested RT-PCR and MMP-2, MMP-9 activity were detected by gelatin zymography. The expression of survivin RNA and matrix metalloproteinase 2 and 9 in bladder cancer was compared with benign and normal cases.Results: Positivity rates of survivin RNA and MMPs zymography were significantly different among the 3 groups. Urine survivin detection by qualitative nested RT-PCR showed 76.1% sensitivity and 95% specificity. The overall sensitivity, specificity of urinary MMP zymography was 67.3%, 90% respectively. The combined use of urine cytology with urine survivin or MMPs zymography increased sensitivity of urine cytology from 50% to 84.7%. The highest sensitivity (95.6%) was obtained on combining the three markers.Conclusion: Survivin RNA and MMPS zymography can be considered as promising noninvasive markers for bladder cancer early detection. Combined use of the three markers improved the sensitivity for detecting bladder cancer.

Divergent regulation of 92-kDa gelatinase and TIMP-1 by HBECs in response to IL-1β and TNF-α

1997 ◽  
Vol 273 (4) ◽  
pp. L866-L874 ◽  
Author(s):  
P. M. Yao ◽  
B. Maitre ◽  
C. Delacourt ◽  
J. M. Buhler ◽  
A. Harf ◽  
...  
Keyword(s):  
Mrna Level ◽  
Primary Cultures ◽  
Gelatin Zymography ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Type I ◽  
Control Mechanisms ◽  
Mrna Levels ◽  
Gelatinase Activity ◽  
Twofold Increase ◽  
Tnf Α

In this study, we addressed the question of whether human bronchial epithelial cells (HBECs) contribute to the regulation of 92-kDa gelatinase activity by secreting tissue inhibitor of metalloproteinase (TIMP)-1. We investigated expression of 92-kDa gelatinase and TIMP-1 in response to lipopolysaccharide (LPS) and to the proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Confluent HBECs from explants were cultured in plastic dishes coated with type I and III collagen. We demonstrated that TIMP-1 was expressed at both the protein and mRNA levels by primary cultures of HBECs. Gelatin zymography of HBEC-conditioned media showed that exposure of HBECs to LPS, IL-1β, or TNF-α induced a twofold increase in the latent form of 92-kDa gelatinase production, as well as its activation. Also, quantitative reverse transcriptase (RT)-polymerase chain reaction (PCR) demonstrated a twofold increase in the 92-kDa mRNA level in response to both cytokines. In contrast, TIMP-1 production evaluated by immunoblotting was unchanged in the presence of LPS and IL-1β and was clearly decreased in the presence of TNF-α. Quantitative RT-PCR demonstrated that TIMP-1 mRNA levels remained unchanged in response to LPS or IL-1β but decreased by 70% in the presence of TNF-α. All of these results strongly suggest that the control mechanisms regulating the expression of 92-kDa gelatinase and TIMP-1 by HBECs in response to inflammatory stimuli are divergent and result in an imbalance between 92-kDa gelatinase and TIMP-1 in favor of the metalloproteinase. Such an imbalance may contribute significantly to acute airway inflammation.

P–664 Bone morphogenetic protein–7 (BMP–7) reduces E2 and P4 production of human luteinized granulosa cells by down-regulating the expression of the steroidogenic enzymes StAR and 3B-HSD

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
C S Yildiz ◽  
O Oktem
Keyword(s):  
Granulosa Cells ◽  
Activin A ◽  
Dependent Manner ◽  
Rt Pcr ◽  
Steroidogenic Enzymes ◽  
In Vivo Models ◽  
Viability Assay

Abstract Study question What is the biological role of BMP–7 on the granulosa cells after luteinization? Summary answer BMP–7 down regulates the steroidogenic enzymes and reduces E2 and P4 output of luteinized granulosa cells. What is known already BMP–7 is a member of TGF-B super family that is mainly produced by theca cells in the ovary. It promotes the transition of primordials into primary follicles, and the growth and preantral and antral follicles, and inhibits progesterone (P4) production during FSH-induced growth phase of Graafian follicles (luteinization inhibitor). However, limited data is available regarding the role of this hormone on the molecular luteal characteristics of granulosa cells after ovulation and luteinization processes. We therefore aimed to address this issue in the current study. Study design, size, duration A basic science study on the corpus luteum biology Participants/materials, setting, methods Human luteal granulosa cells were obtained from 10 normo-responder IVF patients undergoing ovarian stimulation with rec-FSH and GnRH antagonist protocol and cultured with recombinant forms of BMP–7, hCG and activin-A for 24h. The presence of cognate receptors for these hormones were validated using RT-PCR. The expression of the steroidogenic enzymes were analyzed with quantitative immunoblotting, real-time RT-PCR and confocal microscopy. E2 and P4 production of the cells were measured using ECLIA method. Main results and the role of chance BMP–7 significantly down-regulated the expression of StAR and 3b-HSD in immunoblotting and confocal images and caused a substantial decrease in P4 production in the luteal GCs in a dose dependent manner. It did not cause any notable change in aromatase expression, however E2 output declined in parallel with P4 due to the reduced expression of StAR, which is the rate limiting enzyme in steroidogenesis. hCG significantly up-regulated StAR and 3b-HSD expression and enhanced P4 output whereas activin-A did the opposite effect. Viability assay with Yo-PRO–1 uptake assay did not reveal any significant differences in the viability of the cells before and after treatment with these hormones. Limitations, reasons for caution In-vitro findings requires validation using in-vivo models. Wider implications of the findings: Reversal of luteinization and down-regulation of steroidogenesis with BMP–7 and other hormones with similar actions warrant further investigation to test their in-vivo effects in order to develop new strategies against ovarian hyperstimulation syndrome (OHSS). Trial registration number Not applicable

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