Abstract
BackgroundMenopause results in a lack of regular menstrual cycles, leading to the reduction of estrogen production. On the other hand, ovarian androgen synthesis is still present at reduced levels and requires expression of several steroidogenic enzymes.MethodsThis study was performed on 104 postmenopausal women hospitalized due to uterine leiomyomas, endometriosis, and/or a prolapsed uterus. Patients were divided into three groups depending on the time from menopause. Group A patients experienced menopause 1–5 years before enrollment in the study (42 women). Group B included women who had their last menstruation 5–10 years before the study (40 women). Group C consisted of 22 women who were more than 10 years past menopause. Hysterectomy or removal of the uterine corpus with adnexa was performed during laparotomy. We evaluated the expression of aromatase cytochrome P450 (CYP 19) and 17β-hydroxysteroid dehydrogenase (17β HSD) by employing immunohistochemistry.ResultsActivity of 17β-HSD and CYP19 was demonstrated in the cytoplasm of stromal cells of postmenopausal ovaries, epithelium cells coating the ovaries, vascular endothelial cells, and epithelial inclusion cysts. However, overall expression of both 17β-HSD and CYP 19 decreased with time after menopause.ConclusionDemonstration of the activity of the key enzymes of ovarian steroidogenesis, CYP 19 and 17β-HSD, confirms steroidogenic activity in the ovaries of postmenopausal women. Nevertheless, ovarian steroidogenic activity decreases with time, and its significant decrease occurs 10 years after menopause.
Highlights
The key enzymes of ovarian steroidogenesis are hydroxylases and oxidases, which belong to a large family of cytochrome P450 [1,2,3,4] that consists of 480 enzymes, including i) P450scc, which is responsible for cleaving the side chain of cholesterol, ii) P450c11, which mediates the conversion of 11-deoxycorticosterone to corticosterone and possesses 11-hydroxylase, 18-hydroxylase, and 19-methylooxydase activities, iii) P450c17, which mediates 17-hydroxylation of pregnenolone and progesterone
The activity of key enzymes involved in gonadal steroidogenesis, such as 17β-HSD and CYP 19, provides strong evidence for the presence of the steroid biosynthesis in the postmenopausal ovaries
These results indicate a reduction in the activity of gonadal steroidogenesis as a function of time elapsed from menopause
Summary
The key enzymes of ovarian steroidogenesis are hydroxylases and oxidases, which belong to a large family of cytochrome P450 [1,2,3,4] that consists of 480 enzymes, including i) P450scc, which is responsible for cleaving the side chain of cholesterol, ii) P450c11, which mediates the conversion of 11-deoxycorticosterone to corticosterone and possesses 11-hydroxylase, 18-hydroxylase, and 19-methylooxydase activities, iii) P450c17, which mediates 17-hydroxylation of pregnenolone and progesterone, The most important step in women’s steroidogenesis is aromatisation of androgens, which leads to the generation of estrogens. Ovarian androgen synthesis is still present at reduced levels and requires expression of several steroidogenic enzymes
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