R. Misao

Leiomyoma of the Fallopian Tube

Leiomyomas of the fallopian tube are rare. They are typically incidental findings seen at autopsy or unrelated surgical procedures. A 32-year-old woman presented with lower abdominal pain and mass. Transvaginal sonogram and magnetic resonance imaging showed the solid mass at the outside of the uterus. At surgery, the left fallopian tube contained a firm mass with torsion in the area of the ampullary-isthmic junction. The left tube and the infundibulopelvic ligament were rolled in torsion and showed edematous change. We report a rare case in whom torsion of a pedunculated tubal leiomyoma caused abdominal pain.

Expression of sex hormone-binding globulin mRNA in uterine leiomyoma, myometrium and endometrium of human subjects

This study was designed to evaluate the effect of sex hormone-binding globulin (SHBG) on the estrogen-dependent growth of human uterine leiomyoma. Levels of SHBG mRNA were analyzed using competitive reverse transcription-polymerase chain reaction-Southern blot analysis (RT-PCR-SBA). In normal uterine endometria, the levels of SHBG mRNA in the early/mid and late proliferative phases of the menstrual cycle were significantly lower than in the secretory phase (p < 0.01). In uterine myometria and leiomyomas, SHBG mRNA level showed no significant differences during the menstrual cycle, while the ratio of leiomyoma SHBG level to the corresponding myometrium SHBG level was >1 in 21 out of 23 cases (91%). Our results suggest that steroidal regulation of intracellular SHBG synthesis in the myometrium and the leiomyoma might differ from that in the endometrium, and that the mechanism of SHBG expression in leiomyoma might, in the process of tumorigenesis, be altered from that of corresponding normal myometrium, contributing to SHBG overexpression and the abundant estrogen supply.

Localization of sex hormone-binding globulin mRNA expression in human uterine endometrium

To identify the dominant cell of sex hormone-binding globulin (SHBG) synthesis in human uterine endometrium, we investigated the expression of endometrial SHBG mRNA using Northern blot and in situ hybridization analyses. Expression of a single dominant SHBG mRNA was detected in uterine endometrium using Northern blot analysis. Additionally, SHBG mRNA expression was demonstrated by in situ hybridization in the glandular epithelial cells of the endometrium, but not in the stromal cells. Therefore, in the endometrial glandular epithelial cells, SHBG might be involved in the intracellular steroidal action, but not in the endometrial stromal cells. The SHBG-mediated effects on the endometrium appear to be heterogeneous.

Expression of estrogen and progesterone receptors and their mRNAs in ovarian endometriosis

To discover the molecular mechanisms of estrogen-induced growth in ovarian endometriosis, the expression of estrogen and progesterone receptors and their mRNAs was investigated. The expression of estrogen and progesterone receptors and their mRNAs was significantly (p < 0.01) lower in endometriotic endometria than in normal endometria. The ratio of estrogen receptors: progesterone receptors was significantly (p < 0.01) higher in the endometriotic tissues than in normal proliferative- and secretory-phase endometria, as was the ratio of their respective mRNAs. These findings suggest that the absolute and relatively reduced number of estrogen receptors in ovarian endometriosis might cause the loss of control of estrogenic action, and that, furthermore, the relatively increased number of progesterone receptors might lead to an estrogen-dominant milieu, assisting in the development and growth of the ovarian endometriosis.

Levels of sex hormone-binding globulin and corticosteroid-binding globulin mRNAs in corpus luteum of human subjects: correlation with serum steroid hormone levels.

To understand regulation of the function of human ovarian corpus luteum by sex steroid-binding proteins, the levels of luteal intracellular sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) mRNAs and serum steroid hormones were simultaneously determined. The expression of SHBG and CBG mRNAs was detected in all samples analyzed. SHBG mRNA level was positively correlated with serum estradiol-17 beta level (p < 0.05), but not with serum progesterone level. There was a positive correlation between SHBG mRNA level and serum estradiol-17 beta/progesterone ratio (p < 0.01). On the other hand, CBG mRNA level was positively correlated with serum estradiol-17 beta and progesterone level (p < 0.01 and p < 0.01, respectively). There was no correlation between CBG mRNA level and serum estradiol-17 beta/progesterone ratio. SHBG and CBG mRNA levels were not correlated with the levels of serum testosterone, free testosterone or cortisol. These findings suggest that the synthesis of luteal SHBG and CBG is complexly regulated by estrogen and progesterone, and that SHBG and CBG interact with estrogen and progesterone, respectively, for luteal steroidal activity.

Effects of danazol and medroxyprogesterone acetate on estrogen-(estradiol and estriol) specific binding sites in rabbit uterus

In rabbit uterus, the presence of separate specific binding sites for not only estradiol but also estriol has been proposed. These sites may be correlated with an antiestradiol effect. Therefore, this study was designed to investigate the effect of antiestrogenic agents such as danazol and medroxyprogesterone acetate (MPA), especially on the estriol binding sites. Danazol and MPA in combination with estradiol were administered subcutaneously to immature female rabbits daily for 10 days, and resulted in a significant (p < 0.05) decrease in uterine weight and estradiol binding sites in the uterus. Treatment with MPA significantly (p < 0.05) decreased the level of estriol binding sites, but treatment with danazol resulted in this to a minimal extent in the uterus primed by estradiol. MPA did not bind to estradiol and estriol binding sites, while danazol at a high concentration bound to estriol binding sites with some affinity, but not to estradiol binding sites in the uterine cytosol of estrogen-primed rabbits. These results suggest that within the antiproliferative effect of danazol and MPA (an antiestrogenic action on estrogen-stimulated uterine growth) there are likely to be specific differences between some of the possible mechanisms of danazol and MPA in their action at the estriol binding site.

Progestin Regulation in Tumor Growth of Female Genital Tract Cancers

The irregular response to progestins directly in tumor growth might be caused by dominant negative progesterone receptor (PR) mutants and the damage to PR-A expression. Progestin treatment as an anti-angiogenic therapy would be less effective in the PR-mutated tumors. Therefore, various anti-angiogenic inhibitors must be used in progestin-refractory and progestin-dependent tumors.

Sex hormone-binding globulin and corticosteroid-binding globulin mRNA levels in infertile women with luteal phase deficiency

This study was designed to investigate the biological significance in intracellular expression of sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) mRNA in uterine endometrium with luteal phase deficiency (designated as out-of-phase endometrium or low serum progesterone level). The levels of such mRNAs were measured by the quantitative reverse transcription-polymerase chain reaction. Under the normal serum 17 beta-estradiol and progesterone levels in the mid-luteal phase, the levels of SHBG and CBG mRNAs in the out-of-phase endometria were not significantly different from those in the normal endometria. On the other hand, SHBG and CBG mRNA levels in the endometria of low serum midluteal progesterone level were significantly (p < 0.05) reduced and raised, respectively, compared with normal levels. These findings suggest that the synthesis of endometrial steroid-binding proteins in the out-of-phase endometrium is conserved, as that in the in-phase endometrium, whereas the decreased progesterone level might up-regulate CBG expression with down-regulation of SHBG expression.

Endocrine Features in Eutestosteronemic Women with Polycystic Ovaries

We attempted to assess the association between hyperandrogenemia and inappropriate gonadotropin secretion in women with polycystic ovaries (PCO). Thirty-one patients diagnosed as PCO by ultrasonography were divided into two subgroups: 17 with high serum total testosterone (T) level (> or = 0.5 ng/ml) and 14 with normal serum total T level (< 0.5 ng/ml). Both subgroups presented for the complaints of oligomenorrhea and/or hirsutism. The control group consisted of 15 women with regular ovulation for reference data collection. The PCO subjects with normal T, but not those with high T, revealed remarkable depletion of sex hormone binding globulin (SHBG), as compared with control. The PCO subject groups with high and normal serum T did not differ with respect to estrogen level, androgen level, follicle-stimulating hormone and prolactin levels, and SHBG concentration. Solely serum luteinizing hormone (LH) level was observed to be higher in those with high T, as typical features, than another subgroup or control. These data suggest that an increase in bioactive T as a result of decrease in serum SHBG or LH elevation may contribute to ovarian dysfunction in the patient with PCO.