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  1. Article ; Online: It is all About the Chase: Neurosteroidogenesis in Male Rats is Driven by Control of Mating Pace.

    Kohtz, Amy S / Frye, Cheryl A

    Current neuropharmacology

    2022  Volume 21, Issue 7, Page(s) 1606–1616

    Abstract: Background: Masculine sexual behaviors are dependent on androstane-derived steroids; however, the modulatory effects of mating, and of mating control, on androstane neurosteroidogenesis remain largely unknown.: Objective: Herein, we investigated the ... ...

    Abstract Background: Masculine sexual behaviors are dependent on androstane-derived steroids; however, the modulatory effects of mating, and of mating control, on androstane neurosteroidogenesis remain largely unknown.
    Objective: Herein, we investigated the effects of mating control, prior sexual experience, and age on brain region specific neurosteroidogenic responses in male rats.
    Methods: Effects of acute sexual experience were tested in naïve male rats that either remained sexually- naïve, were exposed to a standard mating chamber, or were either given control of the mating pace in a standard mating chamber (male control) or mated wherein the female stimulus rat controlled the mating pace in a paced-mating chamber (female control). Aged (10-12 months) sexually responsive male rats were similarly euthanized from the homecage or engaged in male controlled or female controlled mating. All rats were euthanized immediately following exposure conditions for radioimmunoassay of steroids in midbrain, hypothalamus, hippocampus and cortex.
    Results: Consummatory sexual behavior in male vs. female-controlled mating paradigms was altered by age and prior sexual experience. Male-controlled mating increased androstane neurosteroid metabolism, such that complementary increases in the testosterone (T) metabolite 5α-androstane-3α-17β- diol (3α-diol) in the midbrain and hypothalamus of male rats corresponded to decreases in the prohormone, T. 3α-diol were increased in the hippocampus in response to the context alone, and to a lesser degree in response to mating. Mating diminished neurosteroidogenesis in the cortex. Neurosteroidogenesis was overall reduced in aged male rats compared to naïve controls, however, these effects were more prominent in sexually non-responsive aged male rats.
    Conclusion: Extending previous findings, these results indicate differential production of androstane neurosteroids in a mating exposure, age and brain region dependent manner.
    MeSH term(s) Rats ; Female ; Male ; Animals ; Androstanes/metabolism ; Testosterone/metabolism ; Testosterone/pharmacology ; Brain/metabolism ; Steroids/metabolism ; Reproduction
    Chemical Substances Androstanes ; Testosterone (3XMK78S47O) ; Steroids
    Language English
    Publishing date 2022-10-21
    Publishing country United Arab Emirates
    Document type Journal Article
    ZDB-ID 2192352-8
    ISSN 1875-6190 ; 1570-159X
    ISSN (online) 1875-6190
    ISSN 1570-159X
    DOI 10.2174/1570159X21666221019114535
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Mating Enhances Expression of Hormonal and Trophic Factors in the Midbrain of Female Rats.

    Frye, Cheryl A / Chittur, Sridar V

    Frontiers in behavioral neuroscience

    2020  Volume 14, Page(s) 21

    Abstract: Among female rats, mating enhances neurosteroid formation in the midbrain ventral tegmental area (VTA; independent of peripheral steroid-secreting glands, ovaries, and adrenals). The sources/targets for these actions are not well understood. In ... ...

    Abstract Among female rats, mating enhances neurosteroid formation in the midbrain ventral tegmental area (VTA; independent of peripheral steroid-secreting glands, ovaries, and adrenals). The sources/targets for these actions are not well understood. In Experiment 1, proestrous rats engaged in a mating paradigm, or did not, and the midbrains had been assessed
    Language English
    Publishing date 2020-04-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452960-6
    ISSN 1662-5153
    ISSN 1662-5153
    DOI 10.3389/fnbeh.2020.00021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Learning and the Lifespan: What's Sex Got to Do With It?

    Kohtz, Amy Stave / Frye, Cheryl A

    Frontiers in neuroscience

    2020  Volume 14, Page(s) 216

    Abstract: Engagement in sexual behavior can impact neurosteroidogenesis, in particular production of the prohormone testosterone (T) and likely its subsequent metabolism to 5α-androstane-3α-17β-Diol (3α-Diol) or aromatization to estradiol ( ... ...

    Abstract Engagement in sexual behavior can impact neurosteroidogenesis, in particular production of the prohormone testosterone (T) and likely its subsequent metabolism to 5α-androstane-3α-17β-Diol (3α-Diol) or aromatization to estradiol (E
    Language English
    Publishing date 2020-03-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2020.00216
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Progesterone's Effects on Cognitive Performance of Male Mice Are Independent of Progestin Receptors but Relate to Increases in GABA

    Frye, Cheryl A / Lembo, Vincent F / Walf, Alicia A

    Frontiers in endocrinology

    2021  Volume 11, Page(s) 552805

    Abstract: Progestogens' (e.g., progesterone and its neuroactive metabolite, allopregnanolone), cognitive effects and mechanisms among males are not well-understood. We hypothesized if progestogen's effects on cognitive performance are through its metabolite ... ...

    Abstract Progestogens' (e.g., progesterone and its neuroactive metabolite, allopregnanolone), cognitive effects and mechanisms among males are not well-understood. We hypothesized if progestogen's effects on cognitive performance are through its metabolite allopregnanolone, and not actions via binding to traditional progestin receptors (PRs), then progesterone administration would enhance performance in tasks mediated by the hippocampus and cortex, coincident with increasing allopregnanolone concentrations, brain derived neurotrophic factor (BDNF) and/or muscimol binding of PR knock out (PRKO) and wild-type PR replete mice.
    MeSH term(s) Animals ; Brain-Derived Neurotrophic Factor/physiology ; Cerebral Cortex/physiology ; GABA-A Receptor Agonists/administration & dosage ; Hippocampus/physiology ; Male ; Maze Learning/physiology ; Mice, Knockout ; Muscimol/administration & dosage ; Progesterone/administration & dosage ; Receptors, GABA-A/physiology ; Receptors, Progesterone/genetics ; Receptors, Progesterone/physiology ; Spatial Memory/physiology ; Mice
    Chemical Substances Bdnf protein, mouse ; Brain-Derived Neurotrophic Factor ; GABA-A Receptor Agonists ; Receptors, GABA-A ; Receptors, Progesterone ; Muscimol (2763-96-4) ; Progesterone (4G7DS2Q64Y)
    Language English
    Publishing date 2021-01-11
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2020.552805
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Endocrine-disrupting chemicals: elucidating our understanding of their role in sex and gender-relevant end points.

    Frye, Cheryl A

    Vitamins and hormones

    2014  Volume 94, Page(s) 41–98

    Abstract: Endocrine-disrupting chemicals (EDCs) are diverse and pervasive and may have significant consequence for health, including reproductive development and expression of sex-/gender-sensitive parameters. This review chapter discusses what is known about ... ...

    Abstract Endocrine-disrupting chemicals (EDCs) are diverse and pervasive and may have significant consequence for health, including reproductive development and expression of sex-/gender-sensitive parameters. This review chapter discusses what is known about common EDCs and their effects on reproductively relevant end points. It is proposed that one way that EDCs may exert such effects is by altering steroid levels (androgens or 17-estradiol, E₂) and/or intracellular E₂ receptors (ERs) in the hypothalamus and/or hippocampus. Basic research findings that demonstrate developmentally sensitive end points to androgens and E₂ are provided. Furthermore, an approach is suggested to examine differences in EDCs that diverge in their actions at ERs to elucidate their role in sex-/gender-sensitive parameters.
    MeSH term(s) Animals ; Behavior/drug effects ; Behavior, Animal/drug effects ; Biomedical Research ; Disorders of Sex Development/chemically induced ; Endocrine Disruptors/toxicity ; Environmental Pollutants/toxicity ; Gender Identity ; Humans ; Research Design ; Sex Differentiation/drug effects ; Transsexualism/chemically induced
    Chemical Substances Endocrine Disruptors ; Environmental Pollutants
    Language English
    Publishing date 2014
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 201161-x
    ISSN 2162-2620 ; 0083-6729
    ISSN (online) 2162-2620
    ISSN 0083-6729
    DOI 10.1016/B978-0-12-800095-3.00003-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Central Actions of 3α,5α-THP Involving NMDA and GABA

    Frye, Cheryl A / Qrareya, Alaa / Llaneza, Danielle C / Paris, Jason J

    Frontiers in behavioral neuroscience

    2020  Volume 14, Page(s) 11

    Abstract: The neurosteroid, 5α-pregnan-3α-ol-20-one (known as "allopregnanolone" or 3α,5α-THP), is produced in the midbrain ventral tegmental area (VTA), independent of peripheral sources of progestogens, where it has potential actions at N-methyl-D-aspartate ( ... ...

    Abstract The neurosteroid, 5α-pregnan-3α-ol-20-one (known as "allopregnanolone" or 3α,5α-THP), is produced in the midbrain ventral tegmental area (VTA), independent of peripheral sources of progestogens, where it has potential actions at N-methyl-D-aspartate (NMDA) and GABA
    Language English
    Publishing date 2020-02-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452960-6
    ISSN 1662-5153
    ISSN 1662-5153
    DOI 10.3389/fnbeh.2020.00011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: SETDB1 Triple Tudor Domain Ligand, (

    Uguen, Mélanie / Deng, Yu / Li, Fengling / Shell, Devan J / Norris-Drouin, Jacqueline L / Stashko, Michael A / Ackloo, Suzanne / Arrowsmith, Cheryl H / James, Lindsey I / Liu, Pengda / Pearce, Kenneth H / Frye, Stephen V

    bioRxiv : the preprint server for biology

    2023  

    Language English
    Publishing date 2023-05-10
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.05.10.539986
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Progesterone attenuates depressive behavior of younger and older adult C57/BL6, wildtype, and progesterone receptor knockout mice.

    Frye, Cheryl A

    Pharmacology, biochemistry, and behavior

    2011  Volume 99, Issue 4, Page(s) 525–531

    Abstract: Progesterone may have actions independent of intracellular progestin receptors (PRs) to influence depressive behavior. To investigate this, we examined effects of progesterone (P; 10mg/kg, SC) on the depressive behavior of mice in the forced swim test ( ... ...

    Abstract Progesterone may have actions independent of intracellular progestin receptors (PRs) to influence depressive behavior. To investigate this, we examined effects of progesterone (P; 10mg/kg, SC) on the depressive behavior of mice in the forced swim test (FST). In Experiment 1, subjects were 4 to 6 months old, intact or ovariectomized (OVX) female and intact or gonadectomized (GDX) male, C57/BL6 mice. Progesterone reduced depressive behavior of young diestrous and OVX mice but male mice were impervious to effects of P. In Experiment 2, subjects were intact aged (20-28 months old) C57/BL6 female and male mice. Progesterone reduced depressive behavior of aged female and male C57/BL6 mice, albeit effects were greater among males. In Experiment 3, effects of P were examined in 4 to 6 months old, gonadally-intact, female and male mice that were wildtype or PR knockouts (PRKOs). Progesterone decreased depressive behavior of young adult, wildtype and PRKO mice, which showed greater immobility than did their wildtype counterparts. In Experiment 4, subjects were 18-24 months old wildtype or PRKO mice (Exp 4). Progesterone decreased immobility among wildtype and PRKO mice (which were not different in terms of their baseline depressive behavior). Together these data demonstrate that P decreases depressive behavior of young and older adult C57/BL6, wildtype and PRKO mice, which suggest that acute anti-depressant effects of P may occur independent of actions at "classic" PRs.
    MeSH term(s) Aging/psychology ; Animals ; Antidepressive Agents ; Data Interpretation, Statistical ; Depressive Disorder/psychology ; Female ; Genotype ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity/drug effects ; Orchiectomy ; Ovariectomy ; Progesterone/pharmacology ; Receptors, Progesterone/genetics ; Receptors, Progesterone/physiology ; Sex Characteristics ; Swimming/psychology
    Chemical Substances Antidepressive Agents ; Receptors, Progesterone ; Progesterone (4G7DS2Q64Y)
    Language English
    Publishing date 2011-06-06
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 191042-5
    ISSN 1873-5177 ; 0091-3057
    ISSN (online) 1873-5177
    ISSN 0091-3057
    DOI 10.1016/j.pbb.2011.05.024
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: SETDB1 Triple Tudor Domain Ligand, (

    Uguen, Mélanie / Deng, Yu / Li, Fengling / Shell, Devan J / Norris-Drouin, Jacqueline L / Stashko, Michael A / Ackloo, Suzanne / Arrowsmith, Cheryl H / James, Lindsey I / Liu, Pengda / Pearce, Kenneth H / Frye, Stephen V

    ACS chemical biology

    2023  Volume 18, Issue 8, Page(s) 1846–1853

    Abstract: Increased expression and hyperactivation of the methyltransferase SET domain bifurcated 1 (SETDB1) are commonly observed in cancer and central nervous system disorders. However, there are currently no reported SETDB1-specific methyltransferase inhibitors ...

    Abstract Increased expression and hyperactivation of the methyltransferase SET domain bifurcated 1 (SETDB1) are commonly observed in cancer and central nervous system disorders. However, there are currently no reported SETDB1-specific methyltransferase inhibitors in the literature, suggesting that this is a challenging target. Here, we disclose that the previously reported small-molecule ligand for SETDB1's triple tudor domain, (
    MeSH term(s) Histone-Lysine N-Methyltransferase/metabolism ; Ligands ; Methylation ; PR-SET Domains ; Tudor Domain
    Chemical Substances Histone-Lysine N-Methyltransferase (EC 2.1.1.43) ; Ligands
    Language English
    Publishing date 2023-08-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1554-8937
    ISSN (online) 1554-8937
    DOI 10.1021/acschembio.3c00280
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Research Brief: Self-Reports of a Constellation of Persistent Antiandrogenic, Estrogenic, Physical, and Psychological Effects of Finasteride Usage Among Men.

    Walf, Alicia A / Kaurejo, Shan / Frye, Cheryl A

    American journal of men's health

    2018  Volume 12, Issue 4, Page(s) 900–906

    Abstract: Our research objective is to understand more, through subjective, self-reports on discussion boards/forums, persons' experiences associated with the use of drugs that alter androgen metabolism, such as finasteride. Finasteride is an orally active, ... ...

    Abstract Our research objective is to understand more, through subjective, self-reports on discussion boards/forums, persons' experiences associated with the use of drugs that alter androgen metabolism, such as finasteride. Finasteride is an orally active, specific inhibitor of 5α-reductase, which is localized to many androgen-dependent tissues. Finasteride inhibits the conversion of testosterone (T) to dihydrotestosterone (DHT), and is commonly used to treat benign prostatic hypertrophy (BPH) and male pattern baldness (MPB), both disorders associated with elevated DHT levels and 5α-reductase activity in the prostate and hair follicles, respectively. It is now acknowledged that long-term use and discontinuation of finasteride has adverse effects (AEs); however, these claims have not been well documented. In this study, discussion board posts (forums) were analyzed as self-reports of what finasteride users indicate is problematic for them. Reports were categorized by the age of subjects as well as the types of AEs described: antiandrogenic, estrogenic, central, and nonspecific/severe. A total of 244 cases were recorded and analyzed on the discussion forum on propeciahelp.com . Among these, 74 (32%) cases reported antiandrogenic affects, 43 (19%) reported estrogenic effects, 70 (30%) reported central effects, 11 (5%) reported nonspecific/severe AEs, and 31 (14%) reported AEs in all categories. The categorization of AEs may prompt further investigation into the pathophysiology of post-finasteride syndrome (PFS). Also, subjective reports may engender greater understanding of the perceived lasting AEs of finasteride.
    MeSH term(s) 5-alpha Reductase Inhibitors/adverse effects ; 5-alpha Reductase Inhibitors/therapeutic use ; Administration, Oral ; Adult ; Alopecia/drug therapy ; Cohort Studies ; Estrogens/metabolism ; Exercise/physiology ; Finasteride/adverse effects ; Finasteride/therapeutic use ; Humans ; Male ; Middle Aged ; Prognosis ; Prostatic Hyperplasia/drug therapy ; Psychology ; Retrospective Studies ; Risk Assessment ; Self Report ; Testosterone/metabolism
    Chemical Substances 5-alpha Reductase Inhibitors ; Estrogens ; Testosterone (3XMK78S47O) ; Finasteride (57GNO57U7G)
    Language English
    Publishing date 2018-01-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2275106-3
    ISSN 1557-9891 ; 1557-9883
    ISSN (online) 1557-9891
    ISSN 1557-9883
    DOI 10.1177/1557988317750989
    Database MEDical Literature Analysis and Retrieval System OnLINE

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