Browsing by Author "Price, Thomas M"

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    A Mitochondrial Progesterone Receptor Increases Cardiac Beta-Oxidation and Remodeling.
    (Journal of the Endocrine Society, 2019-02) Dai, Qunsheng; Likes, Creighton E; Luz, Anthony L; Mao, Lan; Yeh, Jason S; Wei, Zhengzheng; Kuchibhatla, Maragatha; Ilkayeva, Olga R; Koves, Timothy R; Price, Thomas M; Price, Thomas M
    Progesterone is primarily a pregnancy-related hormone, produced in substantial quantities after ovulation and during gestation. Traditionally known to function via nuclear receptors for transcriptional regulation, there is also evidence of nonnuclear action. A previously identified mitochondrial progesterone receptor (PR-M) increases cellular respiration in cell models. In these studies, we demonstrated that expression of PR-M in rat H9c2 cardiomyocytes resulted in a ligand-dependent increase in oxidative cellular respiration and beta-oxidation. Cardiac expression in a TET-On transgenic mouse resulted in gene expression of myofibril proteins for remodeling and proteins involved in oxidative phosphorylation and fatty acid metabolism. In a model of increased afterload from constant transverse aortic constriction, mice expressing PR-M showed a ligand-dependent preservation of cardiac function. From these observations, we propose that PR-M is responsible for progesterone-induced increases in cellular energy production and cardiac remodeling to meet the physiological demands of pregnancy.
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    Cannabinoid exposure and altered DNA methylation in rat and human sperm.
    (Epigenetics, 2018-01) Murphy, Susan K; Itchon-Ramos, Nilda; Visco, Zachary; Huang, Zhiqing; Grenier, Carole; Schrott, Rose; Acharya, Kelly; Boudreau, Marie-Helene; Price, Thomas M; Raburn, Douglas J; Corcoran, David L; Lucas, Joseph E; Mitchell, John T; McClernon, F Joseph; Cauley, Marty; Hall, Brandon J; Levin, Edward D; Kollins, Scott H
    Little is known about the reproductive effects of paternal cannabis exposure. We evaluated associations between cannabis or tetrahydrocannabinol (THC) exposure and altered DNA methylation in sperm from humans and rats, respectively. DNA methylation, measured by reduced representation bisulfite sequencing, differed in the sperm of human users from non-users by at least 10% at 3,979 CpG sites. Pathway analyses indicated Hippo Signaling and Pathways in Cancer as enriched with altered genes (Bonferroni p < 0.02). These same two pathways were also enriched with genes having altered methylation in sperm from THC-exposed versus vehicle-exposed rats (p < 0.01). Data validity is supported by significant correlations between THC exposure levels in humans and methylation for 177 genes, and substantial overlap in THC target genes in rat sperm (this study) and genes previously reported as having altered methylation in the brain of rat offspring born to parents both exposed to THC during adolescence. In humans, cannabis use was also associated with significantly lower sperm concentration. Findings point to possible pre-conception paternal reproductive risks associated with cannabis use.
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    Hormonal management of menopausal symptoms in women with a history of gynecologic malignancy.
    (Menopause (New York, N.Y.), 2020-02) Harris, Benjamin S; Bishop, Katherine C; Kuller, Jeffrey A; Ford, Anne C; Muasher, Lisa C; Cantrell, Sarah E; Price, Thomas M

    Objective

    The aim of the study was to review the role of hormone therapy in menopausal patients with breast cancer and gynecologic malignancies.

    Methods

    We searched MEDLINE (via PubMed) using a combination of keywords and database-specific subject headings for the following concepts: menopause, hormone therapy, and cancer. Editorials, letters, case reports, and comments were excluded, as were non-English articles. Additional references were identified by hand-searching bibliographies of included articles. The searches yielded a total of 1,484 citations. All citations were imported into EndNote X9, where they were screened by the authors.

    Results

    In breast cancer survivors, systemic hormone therapy is not recommended, whereas local low-dose estrogen therapy may be considered after discussion with the patient's oncologist. Among endometrial cancer survivors, hormone therapy is considered safe in low-risk cancers but should be avoided in high-risk subtypes. For survivors of epithelial ovarian cancer and cervical cancer, hormone therapy can be considered, but should be avoided in women with estrogen-sensitive histologic subtypes.

    Conclusions

    The risks of hormone therapy should be assessed on an individual basis, with consideration of age, type of hormone therapy, dose, duration of use, regimen, route, and prior exposure. Systemic hormone therapy is not recommended in breast cancer survivors, whereas vaginal low-dose estrogen appears safe. Hormone therapy may be used by endometrial, cervical, and ovarian cancer survivors with low-risk, non-estrogen-receptor-positive subtypes. Video Summary: http://links.lww.com/MENO/A516.