MED12 gene mutations in women with uterine myoma

Uterine leiomyoma (UL) is a benign and most common tumor that affects 20–45% of women of fertile age. In this study, we analyzed the MED12 gene second exon nucleotide sequence from 15 DNA samples extracted from LM of 15 subjects with uterine leiomyoma and 15 DNA samples extracted from peripheral blood leukocytes of the same female subjects. It was shown that somatic mutations in the MED12 gene occur in 73% of cases with deletions of varying sizes and missense mutations being most common at codon 44. Mutations in the MED12 gene could play an indirect role in leiomyoma progression by modifying the activity of other genes that encode proteins involved in growth and tumor progression.     

Calcium metabolism in post-menopausal women

To investigate some parameters involved in postmenopausal calcium metabolism we have measured FSH, LH, estradiol (E2), parathyroid hormone (PTH) calcitonin (CT), 25-hydroxy-vitamin D3 (25-OH-D3), total calcium (CaT) and ionic calcium (Ca++) serum levels in 20 healthy postmenopausal women and 20 premenopausal women. The results reported show that the decrease of estradiol levels are associated with a significant decrease in 25-OH-D3 serum levels, possibly as result of a lower concentration of vitamin D binding protein, which is extremely sensitive to changes in oestrogen levels. The PTH levels were similar in both groups studied, which might be explained together with increased ionic calcium levels in postmenopausal women, by decreased parathyroid sensitivity to the blocking action of Ca++.     

Altered profiles of serum neuroactive steroids in premenopausal women treated for alcohol addiction

Long-term alcohol consumption results in menstrual irregularities due to the inhibition of progesterone secretion. Some progesterone metabolites, including three pregnanolone isomers (PI), abate, while pregnenolone sulfate (PregS) and dehydroepiandrosterone sulfate (DHEAS) increase, alcohol tolerance. The rationale of this study was to evaluate how the neuroactive steroids reflect the impaired progesterone formation in premenopausal women treated for alcohol addiction, and whether detoxification therapy could restore female reproductive functions and psychosomatic stability by reinstatement of the steroid biosynthesis. Accordingly, serum allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one (P3alpha5alpha)), pregnanolone (P3alpha5beta), isopregnanolone (P3beta5alpha) and epipregnanolone (P3beta5beta), progesterone, PregS, pregnenolone, 17alpha-hydroxy-pregnenolone (Preg17), 17alpha-hydroxy-progesterone (Prog17), DHEA, DHEAS, cortisol and estradiol were measured in 20 women during the therapy (start, 3 days, 14 days, 1 month, 4 months), and in 17 controls, using GC-MS or RIA and evaluated by age-adjusted ANCOVA with status and phase of the menstrual cycle (PMC) as factors, and status-PMC interaction. The patients exhibited depressed progesterone, Prog17, PI, and estradiol, a decreased progesterone/pregnenolone ratio, a decreased ratio of neuroinhibiting P3alpha5alpha to neuroactivating PregS, and an elevated PregS and PregS/pregnenolone ratio. The treatment mostly restored the indices. The reduction of neuroinhibiting pregnanolone isomers in the patients is primarily associated with the impairment in ovarian steroid biosynthesis. Nevertheless, changes in enzyme activities connected with the formation of PI and the influence of altered physiological requirements on the balance between endogenous neuroinhibiting and neuroactivating steroids are also likely. The reinstatement of serum estradiol, progesterone, and PI during the therapy demonstrates its favorable effect on both reproductive functions and the psychosomatic stability of the patients.     

子宫动脉栓塞治疗子宫肌瘤伴月经过多的临床研究

目的：回顾分析24例子宫肌瘤伴月经过多患者入介治疗疗效和子宫动脉栓塞安全性。方法：选择24例子宫肌瘤伴月经过多患者进行子宫肌瘤供血动脉的栓塞。结果：插管栓塞动脉率100％,随访20年。治疗后1月,24例患者经月经明显减少,B超随访,3个月子宫肌瘤体积平均缩小30％,随访2年,其中2例行腹腔镜下子宫肌瘤经阴道摘除术,6例子宫肌瘤消失,16例子宫肌瘤体积平均缩小80％,结论：子宫肌瘤行介入治疗疗效肯定,对粘膜下子宫肌瘤及子宫肌瘤伴月经过多患者尤为适宜。     

Lipid and carbohydrate metabolism in premenopausal women given subdermal estradiol implants

Fifteen premenopausal women were studied before and 6 weeks after receiving subcutaneous implants of 100 mg estradiol. Serum estradiol levels doubled; increases were also seen in fasting serum total cholesterol and in high-density lipoprotein cholesterol (HDL). This increase was confined to the HDL2 subfraction, and was not reflected in the HDL apolipoproteins. Low density lipoprotein (LDL) cholesterol levels were unchanged, as were those of apolipoprotein B, the major protein component of LDL. Carbohydrate metabolism was assessed in a subgroup of 12 women. Estrogen implantation reduced fasting plasma glucose levels but did not alter the plasma glucose response to an oral glucose tolerance test. Plasma insulin levels were unchanged both in the fasted state and during the glucose tolerance test. Our findings indicate that parenteral administration of estradiol can alter lipid and carbohydrate metabolism in premenopausal women.     

The expression of aquaporin 1 and 5 in uterine leiomyomata in premenopausal women: a preliminary study

The aim of this study was to investigate the expression of aquaporins (AQPs) in uterine tissues of premenopausal women. We demonstrated for the first time the expression of AQP1, AQP5 and AQP9 in uterine leiomyomata and in the adjacent normal endometrium and myometrium. The expression of AQP1 and 5 was higher in leiomyomata than in unaffected uteri. AQP9 was expressed only in the unaffected endometrium. It is possible that AQP1 and AQP5 contribute to the formation of leiomyomata in premenopausal women.     

超声技术鉴别子宫肌瘤和子宫腺肌病

子宫肌瘤和腺肌病的准确鉴别在妇科临床诊治中有十分重要的意义,各种鉴别诊断技术中,超声技术因其无损性、简便性而成为常规的一种方法。超声成像技术是其中较为成熟的方法。在综述B型成像、彩色血流成像结合脉冲多普勒、彩色血流功率成像和三维彩色功率成像等四种超声成像技术鉴别子宫肌瘤和子宫腺肌病情况的基础上,介绍了两种新的超声鉴别方法：超声弹性检测技术、基于其他声学特征参数检测的组织定征技术。     

Diet and urinary estrogen profile in premenopausal omnivorous and vegetarian women and in premenopausal women with breast cancer

The urinary estrogen profile was studied in the midfollicular phase twice, and diet four times during 1 yr in 10 premenopausal breast cancer (BC) patients consuming an omnivorous normal Finnish diet and in two control groups, one consuming an omnivorous (n = 12) and the other a lactovegetarian (n = 11) diet. Total fat intake in relation to caloric intake was almost identical in all three groups. Only with regard to grain fiber intake did the BC patients differ significantly from both other groups. No differences were found between the groups with regard to urinary excretion of 13 individual estrogens and total estrogens, with the exception of 4-hydroxyestrone (4-OH-E1), which was significantly lower (P less than 0.05) in the BC group than in the vegetarians. A high carbohydrate to protein ratio in the diet had a negative correlation with the excretion of 2-hydroxyestrogens and 2-hydroxyesterone (2-OH-E1) to 4-OH-E1 ratio. The BC group had significantly higher urinary 2-OH-E1 to E1 ratio (P less than 0.05) compared to the vegetarians. The 2-OH-E1 to 4-OH-E1 ratio was highest in the BC group (= 7.1) and differed significantly from that of the omnivores (= 4.3; P less than 0.02) and vegetarians (= 3.6; P less than 0.005). This ratio showed a negative correlation with intake of carbohydrates, starch, total and grain fiber. Urinary excretion of 4-OH-E1 correlated positively with total and grain fiber intake and plasma SHBG. Protein intake correlated positively with urinary 2-methoxy-E1 excretion, and retinol intake positively with catechol estrogen, E1 and E2 excretion. It is concluded that estrogen production and urinary estrogen profile in premenopausal breast cancer patients is normal with the exception of a low 4-OH-E1 excretion and high urinary 2-OH-E1 to 4-OH-E1 ratio. This ratio, which seems to depend on diet, is the only urinary estrogen parameter separating premenopausal BC patients from the control omnivorous and lactovegetarian women.     

Selected zinc metabolism parameters in premenopausal and postmenopausal women with moderate and severe primary arterial hypertension

The aim of this study was to compare zinc (Zn) metabolism parameters in groups of premenopausal and postmenopausal women with moderate and severe primary arterial hypertension. The study included 38 women, of which 15 were premenopausal and 23 were postmenopausal. Postmenopausal women had a positive correlation between total (ERCt-Zn) and oubain-dependent (ERCos-Zn) rate constants of Zn efflux from lymphocyte (k = 0.52). In premenopausal women’s ERCos-Zn was negatively but weakly correlated with serum Zn (Zn-s) (k = 0.35). The Zn ERCt-Zn and ERCos-Zn did not show any correlation with age, as did Zn-s. Lymphocyte Zn correlated negatively with age only in premenopausal women (k = -0.62). The renin-angiotensin-aldosterone system correlated with Zn metabolism parameters. In premenopausal women, plasma renin activity and serum aldosterone showed positive correlations with lymphocyte Zn (Zn-l) (k = 0.63 andk = 0.41, respectively), and in postmenopausal women, it correlated negatively with Zn-s (k = -0.38) and whole aldosterone correlated negatively with ERCos-Zn (k = -0.41). Positive correlations between Zn metabolism parameters and arterial blood pressure in premenopausal women were as follows: ERCt-Zn with diastolic blood pressure (dRR) (k = 0.40) and ERCos-Zn with dRR (k = 0.47). In postmenopausal women, the correlations between ERC-t-Zn and dRR and systolic blood pressure (sRR) were negative (k = -0.53 andk = -0.63, respectively). A similar situation was observed between dRR and sRR and Zn-s (k = -0.40 andk = -0.38, respectively). The body mass index (BMI) was positively correlated with ERCt-Zn in premenopausal women (k = 0.36), whereas in postmenopausal, it was negatively correlated with ERCos-Zn (k = -0.42). For the whole group, negative correlations were seen between ZnS and dRR and sRR (k = -0.36 andk = -0.39, respectively) and between ERCos-Zn and BMI (k = -0.39). The results presented show differences in Zn metabolism in arterial hypertension between premenopausal and post-menopausal women. The role of estrogens in these differences is disscused.     

Esophageal temperature threshold for sweating decreases before ovulation in premenopausal women

The purpose ofthis study was to test the hypothesis that regulated body temperatureis decreased in the preovulatory phase in eumenorrheic women. Six womenwere studied in both the preovulatory phase (Preov-2;days 9-12), which was 1-2days before predicted ovulation when 17-estradiol(E₂) was estimated to peak, andin the follicular phase (F; days2-6). The subjects walked on a treadmill (~225W · m²)in a warm chamber (ambient temperature = 30°C; dew-pointtemperature = 11.5°C) while heavily clothed.E₂, esophageal temperature(T_es), local skin temperatures,and local sweating rate were measured. The estimate of when theE₂ surge would occur was correctfor four of six subjects. In these four subjects,E₂ increased(P  0.05) from 42.0 ± 24.5 pg/mlduring F to 123.2 ± 31.3 pg/ml during Preov-2. RestingT_es was 37.02 ± 0.20°Cduring F and 36.76 ± 0.28°C during Preov-2(P  0.05). TheT_es threshold for sweating wasdecreased (P  0.05) from 36.88 ± 0.27°C during F to 36.64 ± 0.35°C during Preov-2. Both meanskin and mean body temperatures were decreased during rest in Preov-2group. The hypothesis that regulated body temperature is decreasedduring the preovulatory phase is supported.

     

Bone remodelling is reduced by recovery from iron-deficiency anaemia in premenopausal women

Iron-deficiency anaemia (IDA), one of the most common and widespread health disorders worldwide, affects fundamental metabolic functions and has been associated with deleterious effects on bone. Our aim was to know whether there are differences in bone remodelling between a group of premenopausal IDA women and a healthy group, and whether recovery of iron status has an effect on bone turnover markers. Thirty-five IDA women and 38 healthy women (control group) were recruited throughout the year. IDA women received pharmacological iron treatment. Iron biomarkers, aminoterminal telopeptide of collagen I (NTx), procollagen type 1 N-terminal propeptide (P1NP), 25-hydroxyvitamin D, and parathormone (PTH) were determined at baseline for both groups and after treatment with pharmacological iron for the IDA group. IDA subjects were classified as recovered (R) or non-recovered (nR) from IDA after treatment. NTx levels were significantly higher (p <0.001), and P1NP levels tended to be lower in IDA women than controls after adjusting for age and body mass index (BMI), with no differences in 25-hydroxyvitamin D or PTH. After treatment, the R group had significantly lower NTx and P1NP levels compared to baseline (p <0.05 and p <0.001 respectively), whilst no significant changes were seen in the nR group. No changes were seen in 25-hydroxyvitamin D or PTH for either group. IDA is related to higher bone resorption independent of age and BMI. Recovery from IDA has a concomitant beneficial effect on bone remodelling in premenopausal women, decreasing both bone resorption and formation.     

Hypertrophy of the myometrial cells in women with myoma

A rapid growth of the uterus myoma results from the cell hypertrophy, which involves essential ultrastructural changes in the cytoplasm and the nucleus, thus suggesting the intensification cell functions. The increase in the cell volume and intensification of secretion is followed by the enlargement of the interface between the nucleus and the cytoplasm resulting in formation of numerous invaginations of the nuclear membrane. The autoradiographical data demonstrate a considerable DNA synthesis in the peripheral zone of the myoma, unlike the situation seen in the centre of the myoma and the unchanged myometrium, where DNA synthesis is not considerable. The cytospectrophotometric analysis confirms the above data showing the highest content of DNA in the peripheral zone of the myoma.     

Testosterone increases the muscle protein synthesis rate but does not affect very-low-density lipoprotein metabolism in obese premenopausal women

Men and women with hyperandrogenemia have a more proatherogenic plasma lipid profile [e.g., greater triglyceride (TG) and total and low-density lipoprotein-cholesterol and lower high-density lipoprotein-cholesterol concentrations] than healthy premenopausal women. Furthermore, castration of male rats markedly reduces testosterone availability below normal and decreases plasma TG concentration, and testosterone replacement reverses this effect. Testosterone is, therefore, thought to be an important regulator of plasma lipid homeostasis. However, little is known about the effect of testosterone on plasma TG concentration and kinetics. Furthermore, testosterone is a potent skeletal muscle protein anabolic agent in men, but its effect on muscle protein turnover in women is unknown. We measured plasma lipid concentrations, hepatic very low density lipoprotein (VLDL)-TG and VLDL-apolipoprotein B-100 secretion rates, and the muscle protein fractional synthesis rate in 10 obese women before and after trandermal testosterone (1.25 g of 1% AndroGel daily) treatment for 3 wk. Serum total and free testosterone concentrations increased (P < 0.05) by approximately sevenfold in response to testosterone treatment, reaching concentrations that are comparable to those in women with hyperandrogenemia, but lower than the normal range for eugonadal men. Except for a small (～10%) decrease in plasma high-density lipoprotein particle and cholesterol concentrations (P < 0.04), testosterone therapy had no effect on plasma lipid concentrations, lipoprotein particle sizes, and hepatic VLDL-TG and VLDL-apolipoprotein B-100 secretion rates (all P > 0.05); the muscle protein fractional synthesis rate, however, increased by ～45% (P < 0.001). We conclude that testosterone is a potent skeletal muscle protein anabolic agent, but not an important regulator of plasma lipid homeostasis in obese women.     

Calcium diffusion in uterine smooth muscle sheets

The potassium contracture in the longitudinal muscle of estrogen- treated rat uterus was kinetically investigated. The rates of tension development after Ca addition and relaxation after Ca removal were measured under the high-potassium depolarization. Both rates decreased with an increase in preparation thickness. The relaxation rate had only a slight dependence on temperature. On the contrary, both relaxation and contraction rates in a contraction induced by an electrical stimulation strongly depended on temperature, but not on preparation size. These results suggest that the Ca diffusion process in the extracellular space is the rate-limiting step in relaxation of Ca- dependent contracture under potassium depolarization. The diffusion model, in which the effect of the unstirred layer was considered, could quantitatively explain the experimental results. The apparent diffusion coefficient in the muscle sheet was estimated to be approximately 3 x 10(-7) cm2/s. The difference from that in aqueous solution is discussed.     

Unusual fractures associated with osteoporosis in premenopausal women.

Two premenopausal women (aged 40 and 34 years) and multiple undisplaced, often asymptomatic fractures of the femurs, ribs, metatarsals and other bones. The fractures, which appeared on roentgenograms as transverse radiolucent zones with variable callus formation, healed slowly or not at all despite treatment with calcium and vitamin D. They resembled pseudofractures (Looser''s transformation zones) radiologically, but the biochemical and histologic findings were those of idiopathic osteoporosis rather than osteomalacia. Since neither patient had been subjected to unusual stress it was concluded that the fractures had resulted from normal activity in abnormal bone.