tretinoin and Polycystic-Ovary-Syndrome

In this review, we summarize recent advances in understanding vitamin A-dependent regulation of sex-specific differences in metabolic diseases, inflammation, and certain cancers. We focus on the characterization of the aldehyde dehydrogenase-1 family of enzymes (ALDH1A1, ALDH1A2, ALDH1A3) that catalyze conversion of retinaldehyde to retinoic acid. Additionally, we propose a "horizontal transfer of signaling" from estrogen to retinoids through the action of ALDH1A1. Although estrogen does not directly influence expression of Aldh1a1, it has the ability to suppress Aldh1a2 and Aldh1a3, thereby establishing a female-specific mechanism for retinoic acid generation in target tissues. ALDH1A1 regulates adipogenesis, abdominal fat formation, glucose tolerance, and suppression of thermogenesis in adipocytes; in B cells, ALDH1A1 plays a protective role by inducing oncogene suppressors Rara and Pparg. Considering the conflicting responses of Aldh1a1 in a multitude of physiological processes, only tissue-specific regulation of Aldh1a1 can result in therapeutic effects. We have shown through successful implantation of tissue-specific Aldh1a1-/- preadipocytes that thermogenesis can be induced in wild-type adipose tissues to resolve diet-induced visceral obesity in females. We will briefly discuss the emerging role of ALDH1A1 in multiple myeloma, the regulation of reproduction, and immune responses, and conclude by discussing the role of ALDH1A1 in future therapeutic applications.

Topics: Adipocytes; Adipogenesis; Adipose Tissue, White; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase 1 Family; Animals; Body Fat Distribution; Chronic Disease; Cytokines; Diet; Disease Models, Animal; Estradiol; Female; Humans; Obesity; Polycystic Ovary Syndrome; Retinal Dehydrogenase; Retinaldehyde; Risk Factors; Sex Factors; Thermogenesis; Tretinoin

The main goal of the present study is to investigate the effects of retinoic acid and fibroblast growth factor-2 on serum levels of FSH and LH, histology, and apoptosis in the mouse model of Poly Cystic Ovary Syndrome (PCOS).. 80 female NMRI mice have been randomly divided into eight groups. Group 1 received normal saline as a control, and Group 2 received estradiol valerate (EV) at 4 mg/100 g of body weight. Moreover, Groups 3-4 were administered with RA (a dose of 0.05 μg/μl) and FGF2 (a dose of 0.01 μg/kg), respectively. Groups 5 and 6 respectively received the EV plus the RA (0.05 μg/μl) and FGF2 (0.01 μg/kg). Group 7 received the RA and FGF2 at doses corresponding to healthy mice, and Group 8 received the EV plus the RA + FGF2 (similar to previous doses). RA and FGF2 were injected three times per week for four weeks. Finally, histological and immunohistological parameters of the ovary were evaluated.. The study revealed that both single and combined injection of fibroblast growth factor-2 (FGF2) and retinoic acid (RA) in groups 5, 6, and 8 significantly reduced follicular diameters compared to group 2. Measurements confirmed that simultaneous injection of RA and FGF2 into polycystic mice significantly increased antral follicles, corpus luteum (CL), epithelial thickness, and oocyte diameter as well as decreased cystic follicles. Positive TUNEL cells that were considerably increased in the antral follicle of group 2 significantly decreased in the RA and FGF2 recipient groups, either alone or in combination. Besides, the injection of FGF2 increased preantral follicles and CL.. The findings of the present investigation reveal that injection of RA and FGF2 has both protective and ameliorative effects that can promise new therapies for women with PCOS.

Topics: Animals; Apoptosis; Corpus Luteum; Disease Models, Animal; Estradiol; Female; Fibroblast Growth Factor 2; Follicle Stimulating Hormone; Injections, Intraperitoneal; Luteinizing Hormone; Mice; Oocytes; Ovarian Follicle; Polycystic Ovary Syndrome; Protective Agents; Tretinoin

Acne vulgaris is a widely prevalent chronic skin disease. Although multiple treatments are available, acne can sometimes be refractory to these treatments. The use of alternative medical therapies has increased within dermatology and for acne. This case report describes a patient in whom the addition of cedarwood oil was helpful in controlling acne.

Topics: Acne Vulgaris; Adult; Dermatologic Agents; Female; Hidradenitis Suppurativa; Humans; Oils, Volatile; Phytotherapy; Polycystic Ovary Syndrome; Tretinoin

To investigate the regulation of catechol O-methyltransferase (COMT) expression in granulosa cells and assess potential effects of 2-methoxyestradiol (2-ME2) and COMT inhibitors on granulosa cell steroidogenesis and proliferation.. Controlled experimental study in an academic research laboratory.. JC410 porcine and HGL5 human granulosa cell lines were used for in vitro experiments. Effects of 2-ME2 and COMT inhibitor treatment on DNA proliferation and steroidogenesis were assessed by using Hoechst dye and p450SCC-luciferase reporter assays. Effects of dihydrotestosterone (DHT), insulin, and all-trans retinoic acid (ATRA) on COMT messenger RNA expression were investigated by using COMTP1 promoter-luciferase reporter and Northern blot.. Granulosa cell steroidogenesis and proliferation following COMP inhibitor and 2-ME2 treatment. Regulation of COMT expression with DHT, insulin, and ATRA.. 2-Methoxyestradiol had a dual effect on granulosa cell proliferation and p450SCC- luciferase activity; low doses were stimulatory and high doses were inhibitory. Catechol O-methyltransferase inhibitor was associated with up to a 65% increase in JC410 cell number and a maximal 5.6-fold increase in p450SCC-luciferase activity at 20 micromol/L. Dihydrotestosterone, insulin, and ATRA all induced a dose-dependent increase in COMTP1-luciferase transactivation, as well as up-regulated COMT messenger RNA expression in granulosa cells.. Catechol O-methyltransferase expression in granulosa cells was up-regulated by insulin, DHT, and ATRA. Catechol O-methyltransferase product, 2-ME2, decreased, whereas COMT inhibitor increased granulosa cell proliferation and steroidogenesis. These data suggest that COMT overexpression with subsequent increased level of 2-ME2 may lead to ovulatory dysfunction.

Topics: 2-Methoxyestradiol; Animals; Catechol O-Methyltransferase; Catechol O-Methyltransferase Inhibitors; Cell Proliferation; Cells, Cultured; Dihydrotestosterone; Enzyme Inhibitors; Estradiol; Female; Gene Expression Regulation, Enzymologic; Granulosa Cells; Humans; Models, Biological; Ovarian Follicle; Ovulation; Polycystic Ovary Syndrome; RNA, Messenger; Steroids; Swine; Tretinoin

Polycystic ovary syndrome (PCOS) is characterized by ovarian androgen excess and infertility. Recent experiments have suggested that several genes involved in retinoic acid synthesis may be differentially expressed in PCOS theca cells and may contribute to excessive theca-derived androgen production.. The study was performed to examine whether there are differential effects of retinol and retinoids on normal and PCOS theca cell function.. We used in vitro assays.. The study was conducted at the university laboratory.. We studied theca interna cells isolated from normal-cycling women and women with PCOS.. Theca cells were treated with all-trans-retinoic acid (atRA), 9-cis retinoic acid (9-cis RA), or the retinoic acid precursor retinol.. We measured dehydroepiandrosterone, testosterone, and progesterone biosynthesis as well as cytochrome P450 17alpha-hydroxylase (CYP17), cytochrome P450 cholesterol side-chain cleavage, and steroidogenic acute regulatory protein mRNA abundance and promoter function.. Dehydroepiandrosterone production was increased by atRA and 9-cis RA in normal cells and by atRA, 9-cis RA, and retinol in PCOS. Testosterone production was increased by atRA in normal and by atRA, 9-cis RA, and retinol in PCOS. Progesterone production was not altered by retinoid treatment. Retinoids stimulated mRNA abundance and promoter function for CYP17 and steroidogenic acute regulatory protein in both cell types and cytochrome P450 cholesterol side-chain cleavage in normal cells. Retinol stimulated CYP17 mRNA accumulation and promoter function in PCOS but not normal theca cells. P < 0.05 was considered statistically significant.. Differential responses to retinol and retinoids in normal and PCOS theca suggest that altered retinoic acid synthesis and action may be involved in augmented CYP17 gene expression and androgen production in PCOS.

Topics: Alitretinoin; Antineoplastic Agents; Cholesterol Side-Chain Cleavage Enzyme; Dehydroepiandrosterone; Female; Humans; Hyperandrogenism; In Vitro Techniques; Phosphoproteins; Polycystic Ovary Syndrome; Steroid 17-alpha-Hydroxylase; Testosterone; Theca Cells; Tretinoin; Vitamin A

Polycystic ovary syndrome (PCOS) affects 5% of reproductive aged women and is the leading cause of anovulatory infertility. A hallmark of PCOS is excessive theca cell androgen secretion, which is directly linked to the symptoms of PCOS. Our previous studies demonstrated that theca cells from PCOS ovaries maintained in long term culture persistently secrete significantly greater amounts of androgens than normal theca cells, suggesting an intrinsic abnormality. Furthermore, previous studies suggested that ovarian hyperandrogenemia is inherited as an autosomal dominant trait. However, the genes responsible for ovarian hyperandrogenemia of PCOS have not been identified. In this present study, we carried out microarray analysis to define the gene networks involved in excess androgen synthesis by the PCOS theca cells in order to identify candidate PCOS genes. Our analysis revealed that PCOS theca cells have a gene expression profile that is distinct from normal theca cells. Included in the cohort of genes with increased mRNA abundance in PCOS theca cells were aldehyde dehydrogenase 6 and retinol dehydrogenase 2, which play a role in all-trans-retinoic acid biosynthesis and the transcription factor GATA6. We demonstrated that retinoic acid and GATA6 increased the expression of 17alpha-hydroxylase, providing a functional link between altered gene expression and intrinsic abnormalities in PCOS theca cells. Thus, our analyses have 1) defined a stable molecular phenotype of PCOS theca cells, 2) suggested new mechanisms for excess androgen synthesis by PCOS theca cells, and 3) identified new candidate genes that may be involved in the genetic etiology of PCOS.

Topics: Alcohol Oxidoreductases; Aldehyde Dehydrogenase; Androgens; Base Sequence; Cells, Cultured; Cholesterol Side-Chain Cleavage Enzyme; Colforsin; DNA-Binding Proteins; Female; GATA6 Transcription Factor; Gene Expression Profiling; Gene Expression Regulation; Humans; Oligonucleotide Array Sequence Analysis; Phenotype; Phosphoproteins; Polycystic Ovary Syndrome; Promoter Regions, Genetic; RNA, Messenger; Signal Transduction; Steroid 17-alpha-Hydroxylase; Theca Cells; Transcription Factors; Tretinoin