Disease relevance of CYP19

• In summary, the results of this study lead us to conclude that aromatase inhibition in the mature dog causes Leydig cell hypertrophy rather than hyperplasia and increased surface area per Leydig cell of subcellular organelles that contain enzymes involved in steroid biosynthesis [1].
• To determine whether the inhibition of estrogen-related effect in the prostate would be of value in the management of benign prostate hyperplasia (BPH), we examined the effect of TZA-2209, a new steroidal aromatase inhibitor, on the prostate in three of six castrated beagles that received 75 mg/week androstenedione [2].
• Effect of dual inhibition of 5-alpha-reductase and aromatase on spontaneously developed canine prostatic hypertrophy [3].
• The expression of aromatase was lower in seminomas and in mixed tumors [4].

High impact information on CYP19

• In the present study we posed the question of whether the increased testosterone secretion by testes from these same aromatase-treated dogs was due to Leydig cell hypertrophy or hyperplasia, and if the latter, whether cytoplasmic organelles are increased [1].
• The effect of inhibition of aromatase enzyme activity on Leydig cell number and ultrastructure in beagles [1].
• CONCLUSIONS: Dual inhibition of 5-alpha-reductase and aromatase resulted in a significant increase in prostate volume, accompanied by a 3-10-fold increase in serum testosterone levels and a significant increase in testicular volume [3].
• Effect of aromatase inhibitor, TZA-2209, on the prostate of androstenedione-treated castrated dogs: changes in prostate volume and histopathological findings [2].
• We concluded that the aromatase inhibitor effectively antagonized the estrogen-related stromal changes, however, this action was accompanied by stimulation of the glandular component due to the accumulation of androgens, the substrate of the aromatase [2].

Chemical compound and disease context of CYP19

• To evaluate the role of aromatase inhibitors in the treatment of benign prostatic hyperplasia (BPH), the effects of a potent, oral, nonsteroidal aromatase inhibitor [4-(5,6,7,8-tetrahydroimidazo[1,5a]pyridin-5yl)benzonitrile; CGS-16949A, CIBA-GEIGY] on canine BPH have been studied [5].

Biological context of CYP19

• Despite these changes in androgen secretion there was no evidence on any effect of aromatase inhibition upon spermatogenesis [6].
• Enhancement of aromatase gene expression in the mediobasal hypothalamus during anestrus in the beagle bitch [7].
• The relationships among expression of cytochrome p450 aromatase (p450arom) mRNA in the mediobasal hypothalamus (MBH), ovarian aromatase activity, and estrogen secretion were examined throughout the estrous cycle in beagle bitches [7].
• Aromatase positive cells were slightly confirmed in luteal cells in the mid-term of gestation (day 40), whereas, in the late-stage (day 50 and 60), the number of aromatase positive cells had increased [8].

Anatomical context of CYP19

• Synergic inhibitory effects of the aromatase inhibitor 1-methyl-androsta-1, 4-diene-3, 17-dione and the antiandrogen cyproterone acetate on androstenedione-induced hyperplastic effects in the prostates of castrated dogs [9].
• The endocrine effect of this aromatase inhibitor in the male canine is presented in the preceding paper [5].
• The effects of an aromatase inhibitor and of an antiandrogen on the ultrastructure and the expression of a secretory protein (acid phosphatase) and marker proteins for basal cells (keratin) and fibroblasts (vimentin) were studied in the prostate of castrated, androstenedione-treated dogs [10].
• 5 alpha-reductase activity in epithelium and stroma of prostates from intact and castrated dogs treated with androstenedione, the aromatase inhibitor 1-methyl-1,4-androstadiene-3,17-dione, and cyproterone acetate [11].
• Previously, it was reported that inhibition of central nervous system aromatase caused a significant increase in plasma LH in the presence of physiologic testosterone levels (Winter et al, 1983) [12].

Associations of CYP19 with chemical compounds

• The aromatase pathway is suggested to be the main mechanism through which testosterone exerts its action within the BNG [13].
• These studies have demonstrated the suitability of the androstenedione model for testing the efficacy of aromatase inhibitors [9].
• The effectiveness of the aromatase inhibitor 1-methyl-androsta-1, 4-diene-3, 17-dione (1-Methyl-ADD) in antagonizing such estrogen-related alterations was investigated in comparison with a combined treatment of 1-Methyl-ADD and the antiandrogen CPA [9].
• The purpose of this study was to investigate the importance of the conversion of testosterone to estradiol in the control of gonadotropin secretion using the aromatase inhibitor aminoglutethimide (AG) [14].
• Anti-androgen effects of the aromatase inhibitor, atamestane [15].

Other interactions of CYP19

• There was also clear expression of the steroidogenic enzymes 5alpha-reductase, aromatase, and the AR [4].
• These neurones express 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), P450 side-chain cleavage (P450scc), 17 alpha-hydroxylase/c17, 20lyase (P450c17), P450 aromatase (P450arom) and produce pregnenolone, progesterone, dehydroepiandrosterone, androstenedion, oestradion and oestrone [16].

Analytical, diagnostic and therapeutic context of CYP19

• Combined treatment with aromatase inhibitor and antiandrogen resulted in a general atrophy of prostatic acini that was less intense relative to the changes observed after castration [10].
• The study consisted of four groups: a 5-alpha-reductase only group (5RI only, n = 5); a 5RI plus aromatase-inhibitor combination group (5RI + ARI combination, n = 5); a BPH control group (n = 3); and a castration control group (n = 3) [3].
• CPA caused a complete atrophy of the prostate that was also present after treatment with both the aromatase inhibitor and CPA in spite of a striking elevation of the serum testosterone and DHT levels and in spite of the antagonization of the inhibition of testes and epididymal weight induced by androstenedione plus CPA [17].
• Quantification of the RT-PCR products revealed that in mammary tumours a significantly higher expression of aromatase is present in comparison to normal mammary tissue [18].

References