Up-regulation of FSHR expression during gonadal sex determination in the frog Rana rugosa

In vertebrates, gonadal production of steroid hormones is regulated by follicle-stimulating hormone (FSH) and luteinizing hormone (LH) via their receptors designated FSHR and LHR, respectively. We have shown recently that steroid hormones are synthesized in the differentiating gonad of tadpoles during sex determination in the frog Rana rugosa. To elucidate the role of gonadotropins (GTHs) and their receptors in the production of gonadal steroid hormones during sex determination, we isolated the full-length FSHβ, LHβ, FSHR and LHR cDNAs from R. rugosa and determined gonadal expression of FSHR (FSH receptor) and LHR (LH receptor) as well as brain expression of FSHβ and LHβ during sex determination in this species. The molecular structures of these four glycoproteins are conserved among different classes of vertebrates. FSHβ expression was observed at similar levels in the whole brain (including the pituitary) of tadpoles, but it showed no sexual dimorphism during gonadal sex determination. By contrast, LHβ mRNA was undetectable in the whole brain of tadpoles. FSHβ-immunopositive cells were observed in the pituitary of female tadpoles with a differentiating gonad. Furthermore, FSHR expression was significantly higher in the gonad of female tadpoles during sex determination than in that of males, whereas LHR was expressed at similar levels in males and females. The results collectively suggest that FSHR, probably in conjunction with FSH, is involved in the steroid-hormone production during female-sex determination in R. rugosa.     

丙氨瑞林对子宫内膜癌裸鼠移植瘤的生长及FHIT表达的影响

目的观察醋酸丙氨瑞林对子宫内膜癌裸鼠移植瘤生长的抑制作用及可能的作用机制。方法将HEC-1-B细胞注入裸鼠左前肢近腋窝处皮下,选24只雌性荷瘤裸鼠随机分为4组,即低剂量组（18肛g／kg）、中剂量组（36μg／kg）、高剂量组（72μg／kg）和空白对照组（0μg／kg）,采取肌肉注射方式给药4周。将瘤体完整取出,测量体积、绘制生长曲线、计算抑瘤率,并用免疫组织化学法检测瘤组织中FHIT蛋白的表达。结果①随着醋酸丙氨瑞林浓度由低到高,癌细胞受抑制渐趋明显,低、中、高剂量组抑瘤率分别为17．0％、24．1％、42．1％,且与对照组比较差异有统计学意义（P〈0．05）。②免疫组织化学结果显示,各干预组的FHIT蛋白表达水平较对照组明显升高,且组间差异有统计学意义（P〈0．05）。结论醋酸丙氨瑞林对子宫内膜癌皮下移植瘤生长有抑制作用,且呈剂量依赖关系．其机制可能与上调FHIT蛋白表达有关。     

Review of Hormone Replacement Therapy in Girls and Adolescents with Hypogonadism

Girls with either hypo- or hypergonadotropic hypogonadism need treatment with estrogens to initiate puberty and maintain a normal hormonal milieu. The focus of this review is hormone replacement treatment in girls with hypogonadism, to initiate and progress through puberty, and to maintain a healthy hormonal milieu in women. It also addresses what is known in the literature regarding estrogen levels in girls and women, instructive cases, practical tables for reference and application, and thoughts on future directions in this area. It represents a thorough literature review with author opinions and recommendations. Girls with normal ovarian function begin puberty on average at 10.5 years old, although there is variation according to ethnicity and degree of excess weight gain. The aim of estrogen therapy to initiate puberty is to mimic normal onset and rate of progression. On the basis of the currently available literature, when a diagnosis of hypogonadism is established, we recommend initiating treatment between age 11 and 12 years of age, with dose increases approximately every 6 months until adult levels are reached. In some situations, treatment may be delayed to allow time for diagnosis or permit more time for linear growth, or address unique risks found in girls treated for various cancers or blood disorders. When adult dosing is reached, progestins are also used to protect uterine health. This can be combined sequentially, allowing regular menstruation, or combined continuously when menstrual bleeding is not preferred. Treatment is continued until the average age of menopause, again with various considerations for longer or shorter duration on the basis of risk-benefit ratios. Transdermal estrogens are considered the most physiologic replacement and theoretically might have fewer associated risks. We review what is known about risks and outcomes and areas for future research.     

The utility of serum leptin and follicular fluid leptin, estradiol, and progesterone levels during an in vitro fertilization cycle

PURPOSE: To prospectively evaluate serum and follicular fluid leptin, estradiol, and progesterone levels during in vitro fertilization. METHODS: Prospective observational study measuring serum levels at six points during the IVF cycle and follicular fluid at the time of retrieval. RESULTS: Serum leptin and estradiol levels both significantly increased for the individual patients during the IVF stimulation process. None of the leptin levels differed based on pregnancy outcome. BMI significantly correlated with all leptin levels. Follicular fluid estradiol correlated with serum estradiol only in pregnant patients (r = 0.97, p<0.01) and was unrelated in non-pregnant patients (r=-0.15, p=0.81). CONCLUSION: Serum and follicular leptin levels are highly correlated. Leptin levels increase during the IVF cycle and vary between patients based on maternal BMI, but do not correlate with other serum hormone levels or pregnancy outcome. Pregnancy outcome success was reflected in the relationship between follicular fluid and serum levels of estradiol, independent of leptin levels.     

Polyribosome and ribonucleoprotein complex redistribution of mRNA induced by GnRH involves both EIF2AK3 and MAPK signaling

The neuropeptide gonadotropin-releasing hormone stimulates synthesis and secretion of the glycoprotein gonadotropic hormones and activates the unfolded protein response, which causes a transient reduction of endoplasmic reticulum-associated mRNA translation. Hormone-treated cell extracts were fractionated to resolve mRNA in active polyribosomes from mRNA in inactive complexes. Quantitative real-time PCR and expression array analysis were used to determine hormone-induced redistribution of mRNAs between fractions and individual mRNAs were found to be redistributed differentially. Among the affected mRNAs relevant to gonadotropin synthesis, the luteinizing hormone subunit genes Lhb and Cga were enriched in the ribonucleoprotein pool. The MAP kinase phosphatase Dusp1 was enriched in the polyribosome pool. Enrichment of Dusp1 mRNA in the polyribosome pool was independent of the unfolded protein response, sensitive to ERK inhibition, and dependent on the 3′untranslated region. The results show that GnRH exerts translational control to modulate physiologically relevant gene expression through two distinct signaling pathways.     

斑点免疫酶渗滤法检测尿液绒毛膜促性腺激素

为了提供一种简便、快速、可靠的检测尿液绒毛膜促性腺激素（ＨＣＧ）的方法，以自制的抗ＨＣＧβ－亚单位单克隆抗体标记辣根过氧化物酶，用抗ＨＣＧ多克隆抗体包被硝酸纤维素膜，建立了一种检测尿液ＨＣＧ的快速斑点免疫酶渗滤法，并制成试剂盒供应临床。该方法简便，整个检测过程只需２分钟。停经５～７天检测即可获阳性结果，斑点色泽鲜艳，结果易于判断。与一般一步酶联免疫吸附法（ＥＬＩＳＡ）比较，符合率为９８％，消除了一般一步法ＥＬＩＳＡ常见的前带现象。经临床验证１０００例，结果与诊断符合率为１００％。试剂盒置４℃和３７℃分别可保存半年和１０天以上。该试剂盒可作为诊断早早孕的常规试剂盒。     

Sexualhormone und Hypophysen-Gonadenachse bei Frauen mit Leberzirrhose in der Postmenopause

Summary The hormonal status of men with cirrhosis of the liver has been investigated in numerous studies. Little, however, is known about changes of sexual hormones in women afflicted by this disorder. In a study of 31 postmenopausal women (mean age 63±8 years) suffering from cirrhosis of various etiology (alcoholic,n=8; posthepatitic B,n=1; PBC,n=5; cryptogenetic,n=17) the blood levels of estradiol (E2), estrone (E1), androstenedione (A), testosterone (T) and basal and stimulated values of gonadotropins are reported and compared with the data obtained in an agematched control group (n=9). In cirrhosis a significant increase of the median E2 (28 vs 12 pg/ml,P<0.01) was found, whereas the changes of the blood levels of E1 (88 vs 76 pg/ml), A (63 vs 111 ng/dl), and T (0.30 vs 0.15 ng/ml) did not attain statistical significance in comparison to controls. Within the study group, however, a significant positive correlation with the degree of decompensation of cirrhosis (Childscore A–C) was observed for the steroid hormones measured. Thus, in subgroup C the hormone levels are higher than physiologically expected for postmenopausal women. On the other hand the median FSH (32 vs 48 mU/ml,P<0.05) is significantly lower in cirrhosis compared to controls with a trend to decreased values of LH. Very low levels of LH and FSH are found in decompensated cirrhosis. The decrease of LH and FSH can partly be explained by the rise of peripheral hormones (i.e. E2, E1, and in some cases T and A). The response of the gonadotropins to stimulation by 100 µg GnRh generally remains unimpaired. Only a few women with decompensated cirrhosis show a hormonal profile (low gonadotropins in spite of low sexual hormones, reduced stimulation after GnRh) that indicates a disturbance of hypophyseal regulation as a result of a central defect of possible hypothalamic origin.

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Abkürzungsverzeichnis A Androstendion - E1 östron - E2 östradiol - FSH Follikel stimulierendes Hormon - GnRh Gonadotropin Releasinghormon - K Kontrollen - LH Luteotropes Hormon - LZ Leberzirrhose - n Anzahl der Personen - PBC Primär biliäre Zirrhose - T Testosteron