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  1. Article ; Online: Triiodothyronine stimulates steroid and VEGF production in murine Leydig cells via cAMP-PKA pathway.

    Dhole, Bodhana / Gupta, Surabhi / Kumar, Anand

    Andrologia

    2021  Volume 53, Issue 3, Page(s) e13972

    Abstract: Thyroid hormones affect testicular development as well as functions like spermatogenesis and steroidogenesis, thereby influencing male fertility. Our group earlier showed that the stimulatory role of the thyroid hormone, ... ...

    Abstract Thyroid hormones affect testicular development as well as functions like spermatogenesis and steroidogenesis, thereby influencing male fertility. Our group earlier showed that the stimulatory role of the thyroid hormone, T
    MeSH term(s) Animals ; Cyclic AMP ; Cyclic AMP-Dependent Protein Kinases ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Leydig Cells ; Male ; Mice ; Phosphatidylinositol 3-Kinases ; Steroids ; Triiodothyronine ; Vascular Endothelial Growth Factor A/genetics
    Chemical Substances Hypoxia-Inducible Factor 1, alpha Subunit ; Steroids ; Vascular Endothelial Growth Factor A ; Triiodothyronine (06LU7C9H1V) ; Cyclic AMP (E0399OZS9N) ; Cyclic AMP-Dependent Protein Kinases (EC 2.7.11.11)
    Language English
    Publishing date 2021-01-13
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 7280-1
    ISSN 1439-0272 ; 0303-4569
    ISSN (online) 1439-0272
    ISSN 0303-4569
    DOI 10.1111/and.13972
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Calotropis procera extract inhibits prostate cancer through regulation of autophagy.

    Singh, Palak / Dhole, Bodhana / Choudhury, Jaganmoy / Tuli, Anannya / Pandey, Deepak / Velpandian, Thirumurthy / Gupta, Surabhi / Chaturvedi, Pradeep Kumar

    Journal of cellular and molecular medicine

    2024  Volume 28, Issue 6, Page(s) e18050

    Abstract: Current treatment options available for prostate cancer (PCa) patients have many adverse side effects and hence, new alternative therapies need to be explored. Anticancer potential of various phytochemicals derived from Calotropis procera has been ... ...

    Abstract Current treatment options available for prostate cancer (PCa) patients have many adverse side effects and hence, new alternative therapies need to be explored. Anticancer potential of various phytochemicals derived from Calotropis procera has been studied in many cancers but no study has investigated the effect of leaf extract of C. procera on PCa cells. Hence, we investigated the effect of C. procera leaf extract (CPE) on cellular properties of androgen-independent PC-3 and androgen-sensitive 22Rv1 cells. A hydroalcoholic extract of C. procera was prepared and MTT assay was performed to study the effect of CPE on viability of PCa cells. The effect of CPE on cell division ability, migration capability and reactive oxygen species (ROS) production was studied using colony formation assay, wound-healing assay and 2',7'-dichlorodihydrofluorescein diacetate assay, respectively. Caspase activity assay and LDH assay were performed to study the involvement of apoptosis and necrosis in CPE-mediated cell death. Protein levels of cell cycle, antioxidant, autophagy and apoptosis markers were measured by western blot. The composition of CPE was identified using untargeted LC-MS analysis. Results showed that CPE decreased the viability of both the PCa cells, PC-3 and 22Rv1, in a dose- and time-dependent manner. Also, CPE significantly inhibited the colony-forming ability, migration and endogenous ROS production in both the cell lines. Furthermore, CPE significantly decreased NF-κB protein levels and increased the protein levels of the cell cycle inhibitor p27. A significant increase in expression of autophagy markers was observed in CPE-treated PC-3 cells while autophagy markers were downregulated in 22Rv1 cells after CPE exposure. Hence, it can be concluded that CPE inhibits PCa cell viability possibly by regulating the autophagy pathway and/or altering the ROS levels. Thus, CPE can be explored as a possible alternative therapeutic agent for PCa.
    MeSH term(s) Male ; Humans ; Cell Line, Tumor ; Calotropis/chemistry ; Calotropis/metabolism ; Reactive Oxygen Species/metabolism ; Androgens/pharmacology ; Prostatic Neoplasms/drug therapy ; Apoptosis ; Plant Extracts/pharmacology ; Plant Extracts/chemistry ; Autophagy ; Cell Proliferation ; Dental Porcelain ; Titanium ; Metal Ceramic Alloys
    Chemical Substances Procera ; Reactive Oxygen Species ; Androgens ; Plant Extracts ; Dental Porcelain (12001-21-7) ; Titanium (D1JT611TNE) ; Metal Ceramic Alloys
    Language English
    Publishing date 2024-02-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 2074559-X
    ISSN 1582-4934 ; 1582-4934 ; 1582-1838
    ISSN (online) 1582-4934
    ISSN 1582-4934 ; 1582-1838
    DOI 10.1111/jcmm.18050
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: A Novel Antigonadotropic Role of Thyroid Stimulating Hormone on Leydig Cell-Derived Mouse Leydig Tumor Cells-1 Line.

    Dhole, Bodhana / Gupta, Surabhi / Shekhar, Skand / Kumar, Anand

    Annals of the National Academy of Medical Sciences (India)

    2020  Volume 56, Issue 1, Page(s) 30–37

    Abstract: Subclinical hypothyroid men characterized by a rise in only thyroid stimulating hormone (TSH) levels and normal thyroid hormone levels showed a fall in their serum progesterone and testosterone levels. This suggested a role of TSH in regulating Leydig ... ...

    Abstract Subclinical hypothyroid men characterized by a rise in only thyroid stimulating hormone (TSH) levels and normal thyroid hormone levels showed a fall in their serum progesterone and testosterone levels. This suggested a role of TSH in regulating Leydig cell steroidogenesis. Therefore, we investigated the direct role of TSH on steroid production and secretion using a mouse Leydig tumour cell line, MLTC-1. MLTC-1 cells were treated with different doses of TSH isolated from porcine pituitary as well as recombinant TSH. Steroid secretion was measured by radioimmunoassay. The mRNA levels of steroidogenic enzymes were quantitated by real time PCR whereas the corresponding protein levels were determined by Western blot. In MLTC-1 cells, pituitary TSH as well as recombinant TSH inhibited progesterone and testosterone secretion in a dose dependent manner. The inhibitory action of TSH on steroid secretion was unique and not mimicked by other anterior pituitary hormones including FSH and ACTH. Recombinant TSH showed no effect on StAR and CYP11A1, the enzymes catalysing the non-steroidogenic and steroidogenic rate-limiting steps of steroid synthesis respectively. Recombinant TSH was shown to inhibit steroidogenesis in MLTC-1 cells by inhibiting the 3β hydroxy steroid dehydrogenase mRNA and protein levels, the enzyme that catalyses the conversion of pregnenolone to progesterone. This inhibitory effect of TSH is probably direct as both mRNA and protein of the TSH receptor were shown to be present in the MLTC-1 cells.
    Language English
    Publishing date 2020-07-12
    Publishing country India
    Document type Journal Article
    ZDB-ID 632986-x
    ISSN 0379-038X
    ISSN 0379-038X
    DOI 10.1055/s-0040-1709091
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: A Novel Antigonadotropic Role of Thyroid Stimulating Hormone on Leydig Cell-Derived Mouse Leydig Tumor Cells-1 Line

    Dhole, Bodhana / Gupta, Surabhi / Shekhar, Skand / Kumar, Anand

    Annals of the National Academy of Medical Sciences (India)

    2020  Volume 56, Issue 01, Page(s) 30–37

    Abstract: Subclinical hypothyroid men characterized by a rise in only thyroid stimulating hormone (TSH) levels, and normal thyroid hormone levels showed a fall in their serum progesterone and testosterone levels. This suggested a role of TSH in regulating Leydig ... ...

    Abstract Subclinical hypothyroid men characterized by a rise in only thyroid stimulating hormone (TSH) levels, and normal thyroid hormone levels showed a fall in their serum progesterone and testosterone levels. This suggested a role of TSH in regulating Leydig cell steroidogenesis. Therefore, we investigated the direct role of TSH on steroid production and secretion using a mouse Leydig tumor cell line-1 (MLTC-1). MLTC-1 cells were treated with different doses of TSH isolated from porcine pituitary as well as recombinant TSH. Steroid secretion was measured by radioimmunoassay (RIA). The mRNA levels of steroidogenic enzymes were quantitated by real-time polymerase chain reaction (RT-PCR), whereas the corresponding protein levels were determined by western blot. In MLTC-1 cells, pituitary TSH as well as recombinant TSH inhibited progesterone and testosterone secretion in a dose-dependent manner. The inhibitory action of TSH on steroid secretion was unique and not mimicked by other anterior pituitary hormones including follicle stimulating hormone and adrenocorticotropic hormone. Recombinant TSH showed no effect on steroidogenic acute regulatory protein and CYP11A1, the enzymes catalyzing the nonsteroidogenic and steroidogenic rate-limiting steps of steroid synthesis, respectively. Recombinant TSH was shown to inhibit steroidogenesis in MLTC-1 cells by inhibiting the 3-β hydroxy steroid dehydrogenase mRNA and protein levels, the enzyme that catalyzes the conversion of pregnenolone to progesterone. This inhibitory effect of TSH is probably direct as both mRNA and protein of the TSH receptor were shown to be present in the MLTC-1 cells.
    Keywords Leydig cells ; steroidogenesisthyroid stimulating hormone receptor ; thyroid stimulating hormone
    Language English
    Publishing date 2020-01-01
    Publisher Thieme Medical and Scientific Publishers Private Ltd.
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 632986-x
    ISSN 2454-5635 ; 0379-038X
    ISSN (online) 2454-5635
    ISSN 0379-038X
    DOI 10.1055/s-0040-1709091
    Database Thieme publisher's database

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  5. Article ; Online: Triiodothyronine stimulates VEGF expression and secretion via steroids and HIF-1α in murine Leydig cells.

    Dhole, Bodhana / Gupta, Surabhi / Venugopal, Senthil Kumar / Kumar, Anand

    Systems biology in reproductive medicine

    2018  Volume 64, Issue 3, Page(s) 191–201

    Abstract: Leydig cells are the principal steroidogenic cells of the testis. Leydig cells also secrete a number of growth factors including vascular endothelial growth factor (VEGF) which has been shown to regulate both testicular steroidogenesis and ... ...

    Abstract Leydig cells are the principal steroidogenic cells of the testis. Leydig cells also secrete a number of growth factors including vascular endothelial growth factor (VEGF) which has been shown to regulate both testicular steroidogenesis and spermatogenesis. The thyroid hormone, T
    Abbreviations: 8-Br-cAMP: 8-bromo - 3', 5' cyclic adenosine monophosphate; CoCl
    MeSH term(s) Animals ; Cell Line, Tumor ; Gonadal Steroid Hormones/metabolism ; Gonadal Steroid Hormones/secretion ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Leydig Cells/metabolism ; Leydig Cells/secretion ; Male ; Mice ; Triiodothyronine/physiology ; Vascular Endothelial Growth Factor A/biosynthesis ; Vascular Endothelial Growth Factor A/secretion
    Chemical Substances Gonadal Steroid Hormones ; Hif1a protein, mouse ; Hypoxia-Inducible Factor 1, alpha Subunit ; Vascular Endothelial Growth Factor A ; Triiodothyronine (06LU7C9H1V)
    Language English
    Publishing date 2018-02-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 2417234-0
    ISSN 1939-6376 ; 1939-6368
    ISSN (online) 1939-6376
    ISSN 1939-6368
    DOI 10.1080/19396368.2018.1433248
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Thyroid and male reproduction.

    Kumar, Anand / Shekhar, Skand / Dhole, Bodhana

    Indian journal of endocrinology and metabolism

    2014  Volume 18, Issue 1, Page(s) 23–31

    Abstract: Male reproduction is governed by the classical hypothalamo-hypophyseal testicular axis: Hypothalamic gonadotropin releasing hormone (GnRH), pituitary luteinizing hormone (LH) and follicle stimulating hormone (FSH) and the gonadal steroid, principally, ... ...

    Abstract Male reproduction is governed by the classical hypothalamo-hypophyseal testicular axis: Hypothalamic gonadotropin releasing hormone (GnRH), pituitary luteinizing hormone (LH) and follicle stimulating hormone (FSH) and the gonadal steroid, principally, testosterone. Thyroid hormones have been shown to exert a modulatory influence on this axis and consequently the sexual and spermatogenic function of man. This review will examine the modulatory influence of thyroid hormones on male reproduction.
    Language English
    Publishing date 2014-02-13
    Publishing country India
    Document type Journal Article ; Review
    ZDB-ID 2600211-5
    ISSN 2230-9500 ; 2230-8210
    ISSN (online) 2230-9500
    ISSN 2230-8210
    DOI 10.4103/2230-8210.126523
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Role of oxygen in the regulation of Leydig tumor derived MA-10 cell steroid production: the effect of cobalt chloride.

    Kumar, Anand / Rani, Lata / Dhole, Bodhana

    Systems biology in reproductive medicine

    2014  Volume 60, Issue 2, Page(s) 112–118

    Abstract: We have earlier shown that cobalt chloride (CoCl2)-induced hypoxia and second messenger 8-bromoadenosine 3', 5'-cyclic adenosine monophosphate (8-Br-cAMP) stimulates vascular endothelial growth factor (VEGF) production in Leydig tumor cell derived MA-10 ... ...

    Abstract We have earlier shown that cobalt chloride (CoCl2)-induced hypoxia and second messenger 8-bromoadenosine 3', 5'-cyclic adenosine monophosphate (8-Br-cAMP) stimulates vascular endothelial growth factor (VEGF) production in Leydig tumor cell derived MA-10 cells. Both stimuli follow common signal transduction pathways including protein kinase A (PK-A), extracellular regulated kinase 1/2 (ERK1/2), and phosphatidyl inositol-3 kinase/akt (PI3-K/Akt) pathways in the stimulation of VEGF by MA-10 cells. In the present study we investigated the role of CoCl2 and 8-Br-cAMP on steroid production in MA-10 cells. The MA-10 cells were cultured in Waymouth MB 752/1 medium, supplemented with 15% heat inactivated horse serum. Progesterone was estimated by radioimmunoassay (RIA).We report that 8-Br-cAMP stimulated progesterone production by the MA-10 cells whereas CoCl2 inhibited the same. Also, 8-Br-cAMP stimulated steroidogenic acute regulatory protein (StAR) and cytochrome P450 side-chain cleavage enzyme (P450scc) mRNAs expression. However, CoCl2 had no effect on StAR mRNA. Cobalt chloride directly inhibited the expression of P450scc mRNA. The decrease in progesterone production could be attributed to three different mechanisms, (1) an increase in production of reactive oxygen species (ROS), (2) an increase in HIF-1α activity, and (3) ultimately a decrease in the level of cytochrome P450 side chain cleavage (CYT P450scc). Hypoxia has an action and mechanism of action similar to that of gonadotropins on VEGF production, whereas they have a contrasting effect on steroidogenesis. This study suggests that hypoxia could be as important as gonadotropins in regulating Leydig cell steroidogenesis.
    MeSH term(s) Base Sequence ; Cell Line ; Cholesterol Side-Chain Cleavage Enzyme/genetics ; Cobalt/pharmacology ; Culture Media ; DNA Primers ; Humans ; Leydig Cell Tumor/metabolism ; Oxygen/physiology ; Phosphoproteins/genetics ; Progesterone/biosynthesis ; RNA, Messenger/genetics ; Radioimmunoassay ; Reverse Transcriptase Polymerase Chain Reaction
    Chemical Substances Culture Media ; DNA Primers ; Phosphoproteins ; RNA, Messenger ; steroidogenic acute regulatory protein ; Cobalt (3G0H8C9362) ; Progesterone (4G7DS2Q64Y) ; Cholesterol Side-Chain Cleavage Enzyme (EC 1.14.15.6) ; cobaltous chloride (EVS87XF13W) ; Oxygen (S88TT14065)
    Language English
    Publishing date 2014-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2417234-0
    ISSN 1939-6376 ; 1939-6368
    ISSN (online) 1939-6376
    ISSN 1939-6368
    DOI 10.3109/19396368.2013.861034
    Database MEDical Literature Analysis and Retrieval System OnLINE

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