The thyrotropin in hydatidiform moles is human chorionic gonadotropin.

Thyrotropic activity (TSH), measured by the McKenzie mouse bioassay, has been correlated with human chorionic gonadotropin (hCG) activity, measured by radioimmunoassay, in serum and tissue samples from 11 patients with hydatidiform mole and in partially and highly purified preparations of urinary hCG. Serum samples, taken at various times before and after removal of the moles, gave a ratio of 0.42 plus or minus 0.24 muU TSH/U hCG (mean plus or minus SD) (N)=43). In all cases where hCG activity fell below 150-175 U/ml (n=49), thyroid stimulating activity was undetectable (smaller than 40 muU/ml). We extracted lyophylized molar tissue by a modification of the Bates alcohol-saline method and purified the resultant extract by a combination of gel chromatography, affinity chromatography using Concanavalin A coupled to Sepharose, and isoelectrofocusing. Following extraction, an approximately 20-fold purification was achieved without significant alteration of the ratio of the two activities. Using results from all phases of purification the ratio of muU TSH/U hCG was 0.51 plus or minus 0.35(n = 23).Both activities were in the same position on disc gel electrophoresis. Activity ratios were less constant when partially purified preparations of urinary hCG were assayed for both thyrotropic and hCG activities. The presence of an hCG immunoreactive species, presumably hCG-beta subunit, which contains no thyrotropic activity but has an approximately 10-fold greater activity on a weight basis than intact hCG, may be a partial explanation for this observation. Isoelectrofocusing of a urinary hCG preparation showed that all hCG immunoreactive species with pl's between 3. 5 and 5.0 contained thyrotropic activity in proportion to their hCG content. Seven highly purified hCG preparations had thyrotropic activity with a ratio of 0.48 plus or minus 0.18 muU TSH/U hCG. These results indicate that hCG has intrinsic thyrotropic activity. On a molecular basis it is calculated that hCG contains approximately 1/4000 the thyrotropic activity of human pituitary TSH. In conditions of grossly elevated serum hCG levels, such as hydatidiform mole, this thyrotropic activity can be sufficient to produce hyperthyroidism.     

The effects of human chorionic gonadotrophin, progesterone and oestradiol on trophoblast function

Remodelling of the uterine vasculature during the first trimester of human pregnancy requires invasion of trophoblast from the placenta into decidual spiral arterioles. The pregnancy-associated hormones human chorionic gonadotropin (hCG), progesterone (P(4)) and oestradiol (E(2)) are present at high concentrations at the maternal-fetal interface during the remodelling period and thus may contribute to the regulation of trophoblast movement. This study examined the effects of these hormones on trophoblast functions. HTR8/SVneo cells were treated with hCG (5-100mIU/mL), P(4) (20nM-20μM) or E(2) (0.07-734nM). hCG significantly stimulated migration and MMP-9 activity but did not affect cell numbers. P(4) significantly inhibited migration, MMP-2 and -9 activity and reduced cell numbers. E(2) had no effect on migration, MMP activity or cell numbers. We conclude that hCG and P(4), but not E(2), play direct roles in controlling trophoblast invasion, acting as positive and negative stimuli respectively to regulate trophoblast movement during vascular remodelling in early pregnancy.     

Normal human follicle development: an evaluation of correlations with oestradiol, androstenedione and progesterone levels in individual follicles

OBJECTIVE  The mechanism of dominant follicle selection remains obscure.We have investigated the association between follicle diameter and follicular steroid levels in individual human ovarian follicles throughout the menstrual cycle.
DESIGN  Fluid from ovarian follicles ( n  = 326) was obtained in vivo during surgery from 55 regularly cycling women with proven fertility. Follicles were divided into dominant (diameter > 9 mm, n  = 45) and non-dominant (diameter ≤ 9 mm, n  = 281) based on ultrasound measurements.
MEASUREMENTS  Fluid was assayed for oestradiol (E₂), androstenedione (AD), and progesterone (P).
RESULTS  Median P and E₂ levels were significantly lower ( P  < 0.0001) and AD levels significantly higher ( P  = 0.03) in non-dominant as compared to dominant follicles. In non-dominant follicles AD ( r  = 0.14, P  = 0.02), but not P and E₂, levels were correlated to follicular diameter, and significant changes in steroid concentrations across the menstrual cycle were absent. In dominant follicles, diameter was positively correlated with P and E₂ ( P  < 0.001) levels, and inversely correlated with AD concentrations ( P  = 0.01).
CONCLUSIONS  Results indicate that (1) intrafollicular oestradiol concentrations rise only in follicles exceeding 9 mm in diameter and correlate with the diameter of these dominant follicles, suggesting that significant increase in aromatase enzyme activity occurs only in the dominant follicle (2) a cycle-independent accumulation of andro-stenedione with size occurs in non-dominant follicles, and (3) progesterone production occurs in the largest dominant follicles only, suggesting a limited, if any, role for progesterone during follicle development.     

Correlation of serum unconjugated oestriol to red cell 2,3-diphosphoglycerate levels in diabetic pregnancy

In order to evaluate the possible underlying factors for the increase in red cell 2,3-diphosphoglycerate content observed in late diabetic pregnancy, its relationship with serum unconjugated oestriol, human placental lactogen, haemoglobin and hydrogen ion concentrations was investigated in 42 pregnant diabetic women. A significant correlation was found between red cell 2,3-diphosphoglycerate and serum unconjugated oestriol (r = 0.54, p less than 0.001), whereas no correlation was present between 2,3-diphosphoglycerate and the following variables: arterial pH, haemoglobin concentration and human placental lactogen. The content of 2,3-diphosphoglycerate correlated significantly with haemoglobin-oxygen affinity expressed as P50 at pH 7.4 (r = 0.34, p less than 0.05). The results of this study indicate that serum unconjugated oestriol may participate in the regulation of red cell 2,3-diphosphoglycerate content and thereby of the maternal blood oxygen release to the fetus.     

Stimulation of Chinese hamster ovary cells expressing human thyrotropin receptors by serum human chorionic gonadotropin of patients with hydatidiform mole.

We evaluated the stimulation of Chinese hamster ovary cells expressing human thyrotropin receptors (CHO-hTSHR cell) by sera of five patients with hydatidiform mole before and after the evacuation of the mole, and compared the results with serum human chorionic gonadotropin (hCG) concentrations and serum free thyroid hormones in these patients. Significantly increased CHO-hTSHR cell stimulating activities were observed in sera from untreated patients, and the activity decreased promptly after the evacuation of the mole, concomitantly with the decrease in serum hCG and free thyroid hormones. CHO-hTSHR cell stimulating activity of sera of the untreated patients significantly correlated with serum hCG. Moreover, serum hCG stimulated CHO-hTSHR cells in a dose dependent manner similar to the dose-response curve of the stimulation by purified hCG. Sera of the patients and purified hCG did not stimulate nontransfected CHO-K1 cells. However, a significant correlation was not observed between serum-free thyroid hormones and serum hCG or between serum free thyroid hormones and CHO-hTSHR cell stimulating activities in untreated patients. These results indicate that serum hCG from patients with hydatidiform mole stimulates thyroid gland by interacting with TSH receptors, and suggest that the increase in thyroid hormones in patients may depend on both the increased serum hCG and the responsiveness of their thyroid glands to hCG.     

PTEN、VEGF在葡萄胎组织中的表达及临床意义

目的探讨人第10号染色体缺失的磷酸酶及张力蛋白同源的基因(PTEN)、血管内皮生长因子(VEGF)在葡萄胎组织中的表达及意义。方法选择我院手术切除的完全性葡萄胎(CHM)标本20份(CHM组)、部分性葡萄胎(PHM)标本20份(PHM组)、水肿性流产(HA)组织标本30份(HA组)及正常绒毛(NP)标本20份(NP组),采用免疫组化SP法检测各组标本中PTEN、VEGF的表达水平,并分析PTEN、VEGF在各组中表达的相关性。结果CHM组和PHM组PTEN、VEGF阳性表达率均明显高于HA组、NP组,P均<0.05;Spearman等级相关检验示PTEN和VEGF在CHM组、PHM组、HA组、NP组组织中表达均无明显相关性(P均>0.05)。结论 PTEN、VEGF在葡萄胎中的表达变化为其早期诊断提供一定参考依据。