Abstract. Testosterone and 5a-dihydrotestosterone (DHT) are the principal male hormones (androgens) in mammals. The enzyme, steroid 5a reductase catalyzes the conversion of testosterone (T) to its biologically potent steroid (DHT) in androgen dependent tissues. Two 5a reductase isoenzymes have been identified in rat tissues. The type I isoenzyme has been shown to be predominately expressed in the rat liver, whereas androgen target tissues of the genital tract express mainly isoenzyme II. The effects of androgens and glucocorticoids on the abundance of steroid 5a reductase type I (5aR1) messenger RNA in the rat liver were examined. Steady state levels of 5aR1 mRNA decreased dramatically to 1.5% of control levels 14 days following adrenalectomy (ADX), whereas dexamethasone (Dex) administered (0.5 mg/ 100 g) to ADX animals enhanced the expression of 5aR1 to twice its' normal values within 40 hours. Bilateral orchiectomy induced, within eight days, the expression of 5aR1 mRNA in the rat liver to 1.75 fold the normal value while testosterone injection failed to reduce this enhanced expression in castrated animals. Addition of Dex (1 mM) to primary cultures of rat hepatocyte resulted in a five-and three-fold reduction in the mRNA expression of 5aR1 after 24 and 48 hours, respectively. DHT (0.5 mM) however, induced the expression of 5aR1 mRNA by two-and seven-fold 24 and 48 hours post-treatment, respectively. In vitro nuclear run-on analysis of the 5aR1 gene showed no correlation between the rate of synthesis and steady state levels of this mRNA either in the intact liver or in cultured hepatocytes. These results appear to suggest that glucocorticoids and androgens differentially regulate 5aR1 mRNA in the rat liver. Moreover, our findings appear to indicate that regulation of 5aR1 gene is primarily at the post-transcriptional level. TESTOSTERONE and dihydrotestosterone (DHT) are the major circulating androgens in humans and other vertebrates. Although each hormone displays potent effects in biological assays of androgen action, under specific conditions, each hormone displays properties that suggest roles in the modulation of specific functions. It is clear that DHT is crucial for the normal development of the male genitalia and of the prostate [1,2]. In contrast, testosterone appears to play essential roles in promoting spermatogenesis and Wollfian duct development, as well as gonadotropin regulation. The steroid 5a reductase enzyme plays an important physiological role in the conversion of testosterone to its bioactive and reduced derivatives; 5a dihydrotestosterone (DHT) in androgen dependent tissues [3]. To date, two steroid 5a reductase isoenzymes have been cloned and characterized in humans and rats. These isoenzymes are encoded by independent genes designated types I and II. In peripheral tissues such as the liver, type (I) 5a-reductase (5aR1) and reductive 3a-hydroxysteroid dehydrogenase (3a-HSD) isomers work consecutively to eliminate androgens and protect against hormone excess [4]. It has been postulated tha...
Objective To study the role of endometriosis-inducing factor on the differentiation of cultured stem cells into endometrial cells.Methods This was a multicenter prospective cohort casecontrol study where 323 women were examined, but only 134 infertile women were recruited and compiled with the inclusion criteria. The study group comprised 64 women in whom laparoscopy showed endometriotic lesions, and the control group included 70 women free of endometriotic implants. The women's sera were cocultured with mesenchymal stem cells, which were followed up weekly by quantitative real-time PCR to examine the expression of SPARC (secreted protein, acidic, cysteine-rich) and MYC (myelocytomatosis) genes using the 2 ÀDDCt method.Results By coculturing the serum of women with endometriosis and the control group with stem cells, none of the cultures of the sera of women within the control group showed any changes in the normal expression of either SPARC or MYC gene levels. Furthermore, the stem cells were normally multiplying in the same cell line during the entire duration of the study. Nevertheless, stem cells that were cocultured with sera from women with endometriosis showed upregulation of the SPARC gene mRNA with mean respiratory quotient of 3.534 ± 1.129, whereas the MYC gene mRNA was downregulated with a mean respiratory quotient of 0.488 ± 0.104.
ConclusionThe sera of women with endometriosis were able to induce transformation of mesenchymal stem cells into endometrial-like cells on a molecular basis. This evidence supports the endometriosis-inducing factor theory of endometriosis and may have tremendous effect on the therapeutic implications of this debilitating condition.Endometriosis and mir-130a as a potent regulator of gene expression Azmy et al. 3The distribution of mRNA expression of the MYC gene within the study group. There is a decrease in the expression of the MYC gene compared with the control group with a mean RQ of 0.488 ± 0.104. MYC, myelocytomatosis; RQ, respiratory quotient.
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