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Obstetrician & Gynecologist (OB/GYN), Endocrinologist (diabetes, hormones)
26 years of experience
Video profile
Accepting new patients

Education ?

Medical School Score
The University of Texas at Houston (1984)
  • Currently 2 of 4 apples

Awards & Distinctions ?

Awards  
Patients' Choice Award (2012 - 2013)
Compassionate Doctor Recognition (2013)
Top Ten Doctors (2012)
Bell Manor
Obstetrics and Gynecology

Affiliations ?

Dr. Doody is affiliated with 21 hospitals.

Hospital Affilations

Score

Rankings

  • Baylor All Saints Medical Centers
    1400 8th Ave, Fort Worth, TX 76104
    • Currently 4 of 4 crosses
    Top 25%
  • Baylor Regional Medical Center At Grapevine
    1650 W College St, Grapevine, TX 76051
    • Currently 4 of 4 crosses
    Top 25%
  • Texas Health Harris Methodist Hospital Fort Worth
    1301 Pennsylvania Ave, Fort Worth, TX 76104
    • Currently 4 of 4 crosses
    Top 25%
  • Texas Health Harris Methodist Hospital Southwest Fort Worth
    6100 Harris Pkwy, Fort Worth, TX 76132
    • Currently 4 of 4 crosses
    Top 25%
  • Harris Methodist H E B
    1600 Hospital Pkwy, Bedford, TX 76022
    • Currently 4 of 4 crosses
    Top 25%
  • Texas Health Harris Methodist Hospital Azle
    108 Denver Trl, Azle, TX 76020
    • Currently 3 of 4 crosses
    Top 50%
  • Baylor Medical Center at Southwest Fort Worth
    Obstetrician & Gynecologist
    1400 8th Ave, Fort Worth, TX 76104
    • Currently 3 of 4 crosses
    Top 50%
  • Texas Health Presbyterian Hospital Of Dallas
    8200 Walnut Hill Ln, Dallas, TX 75231
    • Currently 3 of 4 crosses
    Top 50%
  • Centennial Medical Center
    12505 Lebanon Rd, Frisco, TX 75035
    • Currently 2 of 4 crosses
  • Plaza Medical Center
    900 8th Ave, Fort Worth, TX 76104
    • Currently 1 of 4 crosses
  • Baylor Med Cntr @ Grapevine
  • Texas Health Fort Worth
  • Harris Continued Care Hospital
    1301 Pennsylvania Ave, Fort Worth, TX 76104
  • Texas Health Resources Harris Heb
  • Texas Health HEB
  • Harris Heb
  • TX Health Harris Methodist Hospital Hurst-Euless-Be
  • Thr Harris Methodist Fort Worth Hospital
  • Harris Methodist - Springwood
    1608 Hospital Pkwy, Bedford, TX 76022
  • Car Laboratory & Surgery Cntr
  • Baylor All Saints City View Swfw
  • Publications & Research

    Dr. Doody has contributed to 20 publications.
    Title Abdominal Myomectomy--a Safe Procedure in an Ambulatory Setting.
    Date December 2010
    Journal Fertility and Sterility
    Excerpt

    To evaluate the efficacy and safety of minilaparotomy myomectomy in an ambulatory setting.

    Title Repetitive Oocyte Donation Does Not Decrease Serum Anti-müllerian Hormone Levels.
    Date August 2010
    Journal Fertility and Sterility
    Excerpt

    To determine if the anti-Müllerian hormone (AMH), a proposed marker of ovarian aging, decreases with repetitive oocyte donation.

    Title Increased Susceptibility to Dextran Sulfate Sodium Induced Colitis in the T Cell Protein Tyrosine Phosphatase Heterozygous Mouse.
    Date May 2010
    Journal Plos One
    Excerpt

    T cell protein tyrosine phosphatase (TC-PTP/PTPN2) is an enzyme that is essential for the proper functioning of the immune system and that participates in the control of cell proliferation, and inflammation. We previously observed that TC-PTP(-/-) mice display various immunodeficiencies, hypersensitivity to LPS and die within three weeks of birth due to anemia and widespread inflammation. A recent analysis of the Wellcome Trust Case Control Consortium (WTCC) genome wide scan data, reported in 2007, indicated a potential role for TC-PTP in inflammatory bowel disease (IBD). To further investigate the potential role of TC-PTP in IBD, we studied heterozygous TC-PTP mutant mice challenged with dextran sulfate sodium (DSS) in their drinking water. In comparison to control animals, we observed significant changes in the colon mucosa of DSS-treated TC-PTP(+/-) mice, in the ratio of colon to body weight, as well as an up-regulation of mRNA transcripts for IL-6, IL-23, 1L-12beta, IFN-gamma, TNF-alpha. Moreover, up-regulation of serum IL-6 levels in DSS-treated TC-PTP(+/-) mice confirms that mice with a single copy of the TC-PTP gene display increased susceptibility to systemic inflammation due to bowel epithelial erosion resulting from DSS challenge. Our findings support the lack of modulation of Janus kinases 1 and 3 (Jak1, Jak3), and the downstream signal transducer and activator of transcription 1,3 and 5 (Stat1, Stat3, Stat 5) by PTPN2 in the development of IBD like condition. Pathological and molecular analysis reveal that the deficiency of TC-PTP results in pro-inflammatory condition in the bowel of heterozygous TC-PTP(+/-) mice. These novel findings in TC-PTP hemi-deficiency support the hypothesis that TC-PTP is an important regulator of inflammatory cytokine signaling and that it may be implicated in the pathophysiology of IBD.

    Title Protein Tyrosine Phosphatases Ptp-1b and Tc-ptp Play Nonredundant Roles in Macrophage Development and Ifn-gamma Signaling.
    Date July 2009
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    The control of tyrosine phosphorylation depends on the fine balance between kinase and phosphatase activities. Protein tyrosine phosphatase 1B (PTP-1B) and T cell protein tyrosine phosphatase (TC-PTP) are 2 closely related phosphatases known to control cytokine signaling. We studied the functional redundancy of PTP-1B and TC-PTP by deleting 1 or both copies of these genes by interbreeding TC-PTP and PTP-1B parental lines. Our results indicate that the double mutant (tcptp(-/-)ptp1b(-/-)) is lethal at day E9.5-10.5 of embryonic development with constitutive phosphorylation of Stat1. Mice heterozygous for TC-PTP on a PTP-1B-deficient background (tcptp(+/-)ptp1b(-/-)) developed signs of inflammation. Macrophages from these animals were highly sensitive to IFN-gamma, as demonstrated by increased Stat1 phosphorylation and nitric oxide production. In addition, splenic T cells demonstrated increased IFN-gamma secretion capacity. Mice with deletions of single copies of TC-PTP and PTP-1B (tcptp(+/-)ptp1b(+/-)) exhibited normal development, confirming that these genes are not interchangeable. Together, these data indicate a nonredundant role for PTP-1B and TC-PTP in the regulation of IFN signaling.

    Title T-cell Protein Tyrosine Phosphatase is a Key Regulator in Immune Cell Signaling: Lessons from the Knockout Mouse Model and Implications in Human Disease.
    Date April 2009
    Journal Immunological Reviews
    Excerpt

    The immune system requires for its proper ontogeny, differentiation, and maintenance the function of several tyrosine kinases and adapters that create and modify tyrosine phosphorylation sites. Tyrosine phosphorylation is a crucial protein modification in immune cell signaling and can be reversed by protein tyrosine phosphatases (PTPs). Much progress has been made in identifying and understanding PTP function in the immune system. In this review, we present one of these proteins, named T-cell PTPs (TC-PTP) (gene name PTPN2), a classical, non-receptor PTP that is ubiquitously expressed with particularly high expression in hematopoietic tissues. TC-PTP is remarkable not only by the fact that it appears to influence most, if not all, cells involved in the development of the immune system, from stem cells to differentiated lineages, but also recent findings have positioned it at the core of several human diseases from autoimmune disease to cancer.

    Title Ptp1b and Tc-ptp: Regulators of Transformation and Tumorigenesis.
    Date July 2008
    Journal Cancer Metastasis Reviews
    Excerpt

    PTP1B and T cell PTP (TC-PTP) are protein tyrosine phosphatases (PTPs) that share high sequence and structural homology yet play distinct physiological roles. While PTP1B plays a central role in metabolism and is an attractive drug target for obesity and type 2 diabetes, TC-PTP is necessary for the control of inflammation. In this review, we will discuss the growing evidence for the involvement of PTP1B in cancer, while proposing a role for TC-PTP in inflammation-induced tumorigenesis. Given the challenge of developing inhibitors specific for PTP1B alone, it is necessary to consider both enzymes and their roles in various cancer models.

    Title Serum Cetrorelix Concentrations Do Not Affect Clinical Pregnancy Outcome in Assisted Reproduction.
    Date January 2008
    Journal Fertility and Sterility
    Excerpt

    OBJECTIVE: To analyze the potential association between serum cetrorelix levels and clinical pregnancy outcome in patients who had undergone assisted reproduction cycles with a GnRH antagonist cetrorelix acetate 3-mg injection. DESIGN: Retrospective case-control study. SETTING: University-affiliated private-assisted reproduction center. PATIENT(S): 130 IVF and intracytoplasmic sperm injection first cycles, treated with the same cetrorelix acetate protocol, in two matched groups according to whether the cycle resulted in clinical pregnancy (n = 56) or not (n = 74). INTERVENTION(S): Cetrorelix acetate administration at 3 mg in a sandwich protocol. MAIN OUTCOME MEASURE(S): Serum cetrorelix concentrations on the day of hCG administration with regard to clinical pregnancy outcome, pre- versus post-hCG percent change in serum E(2) levels and implantation rates. RESULT(S): The cetrorelix serum concentrations were in the range of 0.29 to 5.12 ng/mL. The comparisons between groups with and without clinical pregnancy revealed comparable serum cetrorelix levels. There was no significant correlation between the serum cetrorelix concentrations and percent change in pre- versus post-hCG serum E(2) levels. Serum cetrorelix levels were comparable among patients with various implantation rates. CONCLUSION(S): Although a wide range of serum cetrorelix levels could be detected during a GnRH antagonist cycle, these levels were comparable in patients with and without clinical pregnancies.

    Title Tc-ptp-deficient Bone Marrow Stromal Cells Fail to Support Normal B Lymphopoiesis Due to Abnormal Secretion of Interferon-{gamma}.
    Date July 2007
    Journal Blood
    Excerpt

    The T-cell protein tyrosine phosphatase (TC-PTP) is a negative regulator of the Jak/Stat cytokine signaling pathway. Our study shows that the absence of TC-PTP leads to an early bone marrow B-cell deficiency characterized by hindered transition from the pre-B cell to immature B-cell stage. This phenotype is intrinsic to the B cells but most importantly due to bone marrow stroma abnormalities. We found that bone marrow stromal cells from TC-PTP(-/-) mice have the unique property of secreting 232-890 pg/mL IFN-gamma. These high levels of IFN-gamma result in 2-fold reduction in mitotic index on IL-7 stimulation of TC-PTP(-/-) pre-B cells and lower responsiveness of IL-7 receptor downstream Jak/Stat signaling molecules. Moreover, we noted constitutive phosphorylation of Stat1 in those pre-B cells and demonstrated that this was due to soluble IFN-gamma secreted by TC-PTP(-/-) bone marrow stromal cells. Interestingly, culturing murine early pre-B leukemic cells within a TC-PTP-deficient bone marrow stroma environment leads to a 40% increase in apoptosis in these malignant cells. Our results unraveled a new role for TC-PTP in normal B lymphopoiesis and suggest that modulation of bone marrow microenvironment is a potential therapeutic approach for selected B-cell leukemia.

    Title Late Stages of Embryo Progression Are a Much Better Predictor of Clinical Pregnancy Than Early Cleavage in Intracytoplasmic Sperm Injection and in Vitro Fertilization Cycles with Blastocyst-stage Transfer.
    Date May 2007
    Journal Fertility and Sterility
    Excerpt

    OBJECTIVE: To define and validate metrics of embryo progression and morphology during extended embryo culture and to compare the effects of early cleavage (EC) vs. blastulation stages on clinical pregnancy. DESIGN: Retrospective observational study. SETTING: University-affiliated assisted reproduction center. PATIENT(S): One thousand two hundred ninety-two intracytoplasmic sperm injection and 842 IVF blastocyst-transfer cycles. INTERVENTION(S): The embryo progression index (EPI) was calculated as the area under the curve of total cell number (TCN) over time, by using observed TCN for cleavage-stage embryos and estimated blastocyst TCN according to morphology. The EPI from days 1-3 measured early cleavage, and blastulation was assessed by EPI over extended embryo culture. Blastocyst morphology was converted into numerical blastocyst quality scores (BQSs). Receiver operating characteristic curve analysis was used to evaluate predictors for clinical pregnancy. MAIN OUTCOME MEASURE(S): Clinical pregnancy. RESULT(S): Per-cycle mean EPI and mean BQS for all embryos developing into blastocysts, as well as mean BQS of the transferred embryos, were significant predictors of clinical pregnancy in intracytoplasmic sperm injection and IVF cycles. Mean EPI for days 1-3 did not predict outcome. CONCLUSION(S): Early cleavage is a putative marker of embryo quality. Late-stage embryo development is more sensitive and specific in predicting clinical pregnancy than is early cleavage, supporting the use of extended embryo culture for embryo selection. The embryo progression index and BQS may also be used for this purpose.

    Title Precycle Administration of Gnrh Antagonist and Microdose Hcg Decreases Clinical Pregnancy Rates Without Affecting Embryo Quality and Blastulation.
    Date October 2006
    Journal Reproductive Biomedicine Online
    Excerpt

    The outcome of a novel protocol utilizing precycle gonadotrophin-releasing hormone (GnRH) antagonist administration and LH activity support with microdose recombinant human chorionic gonadotrophin (HCG) was compared to GnRH agonist long protocol used in patients undergoing their first ICSI (n=707) or IVF (n=571) cycles, which had resulted in one or two blastocyst transfers. In GnRH antagonist cycles, cetrorelix acetate (3 mg) was administered s.c. 4 days before FSH stimulation and a repeat dose was given when the lead follicular diameter was 13-14 mm. LH support was provided by recombinant HCG (2.5 microg). Embryo progression and blastulation were evaluated using embryo progression indices and blastocyst quality scores. The tested protocol demonstrated reduced implantation and clinical pregnancy rates as compared with GnRH agonist long protocol, although the embryo progression and blastulation parameters and blastocyst quality were comparable among the groups. Logistic regression models further supported the significant negative impact of GnRH antagonist/microdose HCG protocol on clinical pregnancy rates in both ICSI and IVF patients. Assisted reproduction cycles with fresh blastocyst transfers utilizing precycle GnRH antagonist administration and microdose HCG support resulted in lower implantation and clinical pregnancy rates as compared with GnRH agonist cycles, although the embryo progression and blastulation parameters were comparable.

    Title Use of Recombinant Human Chorionic Gonadotropin in Ovulation Induction.
    Date June 2003
    Journal Fertility and Sterility
    Excerpt

    To review the use of hCG and to describe the clinical benefit of recombinant hCG (r-hCG) based on the published results of prospective, randomized studies. Review of published articles. Tertiary infertility care center.None.None. Oocyte number and quality, luteal phase progesterone, pregnancy and OHSS rate, and local tolerability. The published data consistently show that single doses of 250 microg r-hCG and 5,000 IU urinary (u)-hCG produce similar clinical outcomes when used in infertility treatment cycles for timed intercourse, IUI, and IVF in terms of the number of oocytes retrieved, number of mature oocytes harvested, and fertilization and pregnancy rates attained. Single doses of 10,000 IU u-hCG also gave results comparable to single doses of 250 microg r-hCG. P levels in the midluteal phase were significantly higher with the use of r-hCG compared with u-hCG, and local injection site adverse effects were significantly less frequent, demonstrating the higher purity of the recombinant product. A single 500-microg dose of r-hCG led to a higher rate of ovarian hyperstimulation syndrome compared with a 250-microg dose, with no significant improvement in pregnancy rates.A single dose of 250 microg r-hCG was at least as effective as single doses of 5,000 or 10,000 IU u-hCG but offered the advantages associated with use of a recombinant product: local injection site adverse effects were significantly less frequent with r-hCG than with u-hCG.

    Title Successful Day 5 Embryo Transfer and Pregnancies Resulting After Transport of Embryos by Air for Biopsy and Genetic Analysis.
    Date May 2002
    Journal Journal of Assisted Reproduction and Genetics
    Excerpt

    Case studies of four in vitro fertilization (IVF) cycles where embryo transport by commercial airline followed by biopsy and genetic analysis with subsequent culture to Day 5 and resulting ongoing pregnancy.

    Title Extended Embryo Culture in Human Assisted Reproduction Treatments.
    Date July 2001
    Journal Human Reproduction (oxford, England)
    Excerpt

    In order to evaluate the niche of extended embryo culture in an IVF programme, retrospective analysis of non-selected IVF patients, who underwent ovarian stimulation from April 1998 to June 1999 in a single private practice assisted reproductive technology centre, was performed. Embryos were cultured for 48 h in S1/G1.2 medium followed by 48 to 72 h of culture in S2/G2.2 to day 5 or day 6. Only fertilized oocytes exhibiting two pronuclei from donor and non-donor IVF and intracytoplasmic sperm injection (ICSI) cases were examined to determine the relationship between embryo cell number on day 3 and subsequent rate of blastocyst formation. Results indicated that a proportional relationship existed between the number of blastomeres present in day 3 embryos and the rate of blastocyst formation. Fifty-four per cent of embryos that had six cells on day 3 formed blastocysts, while 76% of those embryos with eight cells formed blastocysts. Blastocyst development did not increase further when embryos had more than eight cells on day 3, indicating that embryos with greater cell numbers on day 3 are not always predictive of a greater likelihood of blastocyst formation. Fertilized oocytes exhibiting two pronuclei from donors produced significantly more blastocysts (67%) than those from IVF patients (52%; P < 0.01), and had a significantly higher implantation rate (54%) compared with IVF patients (30%; P < 0.01). Furthermore, blastocyst cryopreservation resulted in significantly higher implantation rates than cryopreserved cleavage stage embryos (P < 0.001).

    Title Introduction of Blastocyst Culture and Transfer for All Patients in an in Vitro Fertilization Program.
    Date December 1999
    Journal Fertility and Sterility
    Excerpt

    To evaluate the nonselective application of extended embryo culture on the outcome of IVF.

    Title Regulation of Expression of the 3 Beta-hydroxysteroid Dehydrogenases of Human Placenta and Fetal Adrenal.
    Date February 1994
    Journal The Journal of Steroid Biochemistry and Molecular Biology
    Excerpt

    The appropriate expression of 3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase (3 beta-HSD) is vital for mammalian reproduction, fetal growth and life maintenance. Several isoforms of 3 beta-HSD, the products of separate genes, have been identified in various species including man. Current investigations are targeted toward defining the processes that regulate the levels of specific isoforms in various steroidogenic tissues of man. High levels of expression of 3 beta-HSD were observed in placental tissues. It has been generally considered that the multinucleated syncytiotrophoblastic cells are the principal sites of 3 beta-HSD expression and, moreover, that 3 beta-HSD expression is intimately associated with cyclic AMP-promoted formation of syncytia. Herein we report the presence of 3 beta-HSD immunoreactive and mRNA species in uninucleate cytotrophoblasts in the chorion laeve, similar to that in syncytia but not cytotrophoblast placenta. In vitro, 3 beta-HSD levels in chorion laeve cytotrophoblasts were not increased with time nor after treatment with adenylate cyclase activators, whereas villous cytotrophoblasts spontaneously demonstrated progressive, increased 3 beta-HSD expression. Moreover, 3 beta-HSD synthesis appeared to precede morphologic syncytial formation. Thus high steroidogenic enzyme expression in placenta is not necessarily closely linked to formation of syncytia. Both Western immunoblot and enzymic activity analyses also indicated that the 3 beta-HSD expressed in these cytotrophoblastic populations was the 3 beta-HSD type I gene product (M(r), 45K) and not 3 beta-HSD type II (M(r), 44K) expressed in fetal testis. In cultures of fetal zone and definitive zone cell of human fetal adrenal, 3 beta-HSD expression was not detected until ACTH was added. ACTH, likely acting in a cyclic AMP-dependent process, induced 3 beta-HSD type II activity and mRNA expression. The higher level of 3 beta-HSD mRNA in definitive zone compared with fetal zone cells was associated with parallel increases in cortisol secretion relative to dehydroepiandrosterone sulfate formation.

    Title 3 Beta-hydroxysteroid Dehydrogenase Activity in Glandular and Extraglandular Human Fetal Tissues.
    Date December 1991
    Journal The Journal of Clinical Endocrinology and Metabolism
    Excerpt

    The expression of 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) in steroidogenic tissues is an absolute requirement for mammalian reproduction, fetal growth, and life maintenance. We sought to identify extraglandular tissue sites in the human fetus where 3 beta HSD is expressed. To this effect, we conducted in vitro studies by use of homogenates prepared from second trimester fetal tissues. To facilitate the determination of 3 beta HSD activity, an abbreviated technique was developed that consisted in the use of [3 alpha-3H]dehydroepiandrosterone [( 3 alpha-3H]DHEA) as the substrate and NAD+ as the cofactor. With these reagents, the enzymatic reaction leads to the production of both nonradiolabeled androstenedione and NAD3H in equimolar amounts, and the radioactivity associated with NAD3H is used for quantification of 3 beta HSD activity. The kinetic isotope effect introduced by substitution of tritium for hydrogen at the C-3 alpha position of DHEA, determined with six different tissues, was 2.5 +/- 0.7 (mean +/- SD). The specific activities of the enzyme in peripheral tissues and ovary were relatively low, in the range of 0.03 nmol/mg protein.h for stomach (n = 2) to 0.18 +/- 0.14 nmol/mg protein.h for liver (mean +/- SD; n = 13), while in fetal testis and placenta the specific activities were relatively high, viz. 3.4 +/- 0.7 nmol/mg protein.h (mean +/- SD; n = 4) and 2.8 +/- 1.8 nmol/mg protein.h (mean +/- SD; n = 13), respectively. The findings of this study serve to demonstrate that 3 beta HSD is distributed widely among tissues of the human fetus. Although the enzymatic activity was easily demonstrated in peripheral tissues by the use of radiolabeled DHEA as the substrate, 3 beta HSD protein was not readily detected by Western analysis.

    Title The Use of Rat Leydig Tumor (r2c) and Human Hepatoma (hepg2) Cells to Evaluate Potential Inhibitors of Rat and Human Steroid Aromatase.
    Date July 1991
    Journal Journal of Enzyme Inhibition
    Excerpt

    The efficacies of 10-propargylestr-4-ene-3,17-dione (PED), 4-hydroxyandrostenedione (4-OHA) and the imidazole broad spectrum antimycotic drugs, econazole, imazalil, miconazole and ketoconazole, to inhibit the steroid aromatase activities of rat Leydig tumor (R2C) cells and human hepatoma (HEPG2) cells have been determined. The analysis of inhibition of steroid aromatase activity of intact cells provided further insight into the potential use of such drugs to block cellular estrogen synthesis. The IC50 values for the inhibition of aromatase activity of R2C cells by econazole, imazalil, miconazole, ketoconazole, 4-OHA and PED were 4, 9, 40, 1100, 11 and 10 nM, respectively. These drugs also inhibited the steroid aromatase activity of HEPG2 cells with corresponding IC50 values of 13, 27, 20, 15000, 2 and 2 nM, respectively; these findings were suggestive that the steroid aromatase of rat has many similarities to the human enzyme in its interaction with putative inhibitory compounds. Importantly, however, ketoconazole inhibited the rat aromatase more effectively than it did the human enzyme, while PED and 4-OHA were less effective inhibitors of the rat enzyme compared to that of human. These findings indicate differences in the potencies of various drugs to inhibit estrogen biosynthesis in human and rat cells. These may relate to differences in the two aromatase systems and/or differences in the stability of the drugs in the human hepatoma and rat Leydig tumor cells.

    Title Amenorrhea.
    Date December 1990
    Journal Obstetrics and Gynecology Clinics of North America
    Excerpt

    Amenorrhea, the lack of menstruation, is a gynecologic disorder that may arise from a variety of causes. If a logical and orderly schema is followed, the correct diagnosis and appropriate management plan can be formulated.

    Title 3 Beta-hydroxysteroid Dehydrogenase/isomerase in the Fetal Zone and Neocortex of the Human Fetal Adrenal Gland.
    Date May 1990
    Journal Endocrinology
    Excerpt

    The fetal zone of the human fetal adrenal (HFA) gland is established to have decreased 3 beta-hydroxysteroid dehydrogenase/delta 4-5 isomerase (3 beta HSD) activity compared to the neocortex or definitive zone. 3 beta HSD activity, however, can be induced in primary cell culture through treatment with ACTH. Therefore, the HFA with two distinct steroidogenic zones with differences in 3 beta HSD activity as well as the capacity to increase 3 beta HSD activity in response to ACTH provides an excellent model to study the regulation of this enzyme. The presence of 3 beta HSD in the fetal and neocortex zones of the HFA was examined using a polyclonal antibody raised against purified human placental microsomal 3 beta HSD. After homogenates of the fetal and neocortical zones of the HFA were electrophoresed on a sodium dodecyl sulfate-polyacrylamide gel and immunoblotted, the presence of the 3 beta HSD protein with a molecular size of 45 kDa could be demonstrated only in the neocortical zone. ACTH treatment (greater than 2 days) of fetal and neocortical zone explant cultures produced increases in cortisol secretion associated with the respective levels of immunodetectable 3 beta HSD protein. Cortisol and dehydroepiandrosterone sulfate were the respective principal steroid products of neocortical and fetal zone explants. After ACTH treatment, immunodetectable 3 beta HSD was induced to a greater magnitude in the neocortex. These findings provide evidence that the lack of 3 beta HSD activity in the fetal zone, previously considered to be the result of the presence of an endogenous inhibitor, is due to an absence of the protein in this portion of the gland. The lack or minimal expression of 3 beta HSD in the fetal zone of HFA may be due to the action (or lack thereof) of a tissue-specific factor regulating the synthesis of 3 beta HSD.

    Title T Cell Protein Tyrosine Phosphatase Deficiency Results in Spontaneous Synovitis and Subchondral Bone Resorption in Mice.
    Date
    Journal Arthritis and Rheumatism
    Excerpt

    T cell protein tyrosine phosphatase (TC-PTP) is an important regulator of hematopoiesis and cytokine signaling. Recently, several genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) in the locus of TC-PTP that are associated with rheumatoid arthritis and juvenile idiopathic arthritis, among other autoimmune diseases. The aim of this study was to evaluate the effect of TC-PTP deficiency on the bone and joint environment using a knockout mouse model.

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