Estrogen biosynthesis in human uterine adenomyosis

Abstract

Abstract. Estrogen biosynthesis (aromatase activity) was investigated in human adenomyosis tissue and compared with that of the normal myometrium, endometrium, and endometrial cancer tissues. Homogenates were incubated with [1,2,6,7-3H]androstenedione and NADPH at 37° C for 1 h. After stopping the enzymatic reaction with ethyl acetate, [4-14C]estrone and [4-14C]estradiol-17β were added to the incubated sample. Estrone and estradiol were purified and identified by Bio-Rad AG1-X2 column chromatography, thin-layer chromatography and co-crystallization. Estrogen formed in the incubated sample was calculated from the 3H/14C ratio of the final crystal. The value for estrone formed from androstenedione was 52–132 fmol· h −1 · g−1 wet weight. Aromatase activity in the adenomyosis tissues was higher than that in normal endometrial or myometrial tissues, but lower than that found in myometrial or endometrial tumour tissue. Furthermore, we investigated the effect of danazol, progesterone, and medroxyprogesterone acetate on adenomyosis cells in primary cultures. Aromatase activity in adenomyosis was blocked by danazol, but stimulated by progesterone and MPA. These results indicate that aromatase activity in adenomyosis may contribute to the growth of the ectopic endometrial tissue which occurs in this disease.

The pathophysiology of uterine adenomyosis: an update

“…Steroid hormones have also been implicated in the pathogenesis of uterine adenomyosis, and local rather than systemic hyperestrogenism may be implicated (71). This may be through the action of aromatase on androgen precursors (72) or estrone sulphatase acting to convert estrone-3-sulphate to estrone (73); mRNA for aromatase cytochrome P450 was localized in adenomyotic tissue homogenate, and the P450 aromatase protein was localized in adenomyosis glands (74).…”

Association of polymorphisms and haplotypes in the cytochrome P450 1B1 gene with uterine leiomyoma: A case control study

“…Whether ovarian steroid hormones play an essential role in the growth of leiomyoma is unknown. The mitogenic effects of steroid hormones are induced through their receptors or by regulation of growth factor expression (7,8). The UL development possibly occurs in response to a certain type of injury to the myometrium, such as hypoxia (21).…”

“…Evidence has shown that leiomyoma tissue is more sensitive to estrogen compared to myometrium and the concentration of estrogen in leiomyoma tissue is higher compared to the normal myometrium. Additionally, the leiomyoma growth is regulated by serum estrogen and estrogen in the tumor (7).…”

Treatment of Endometrial Hyperplasia with a Danazol-Releasing Intrauterine Device: A Prospective Study

“…In brief, danazol probably interacts with estrogen, progesterone and/or androgen receptors [18][19][20][21] and directly inhibits enzymes such as 3ß-hydroxysteroid dehydogenase, aromatase, and 17ß-hydroxysteroid dehydrogenase, which are involved in estrogen synthesis, which may have an impact on the growth of endometrial cancer [22][23][24].…”