Plac1, a placenta-specific gene, is expressed exclusively by cells of trophoblastic lineage in the mouse, and maps to a region of the X chromosome known to be important in placental growth. These studies were undertaken to define the cellular location of the mRNA for the human orthologue, PLAC1, within the human placenta, and to examine its expression throughout gestation. By Northern analysis, PLAC1 mRNA was detected in term human placenta, migrating as a single 1.7 kb transcript, but in no other fetal or adult tissues tested. Expression was observed throughout gestation, whereas mouse Plac1 is significantly reduced after 12.5 dpc. Using an 35 S-labeled riboprobe, PLAC1 expression was trophoblast-specific at all stages of gestation (8-41 weeks); no expression was seen in cells within the stromal compartment or decidua. Using BeWo choriocarcinoma cells as a trophoblast model, keratinocyte growth factor (KGF) stimulated steady-state PLAC1 mRNA expression approximately twofold by Northern analysis and quantitative real-time PCR. Stimulation was observed only after 24 hr of exposure, suggesting that the stimulatory effect of KGF is secondary to the promotion of trophoblast growth or differentiation. No change in mRNA levels resulted from exposure to insulin-like growth factor II (IGF-II). Trophoblast-specific expression throughout gestation and responsiveness to KGF are consistent with a fundamental role for PLAC1 at the maternal-fetal interface.

The LH biological potency of the International Reference Preparation (IRP) of Human Pituitary LH for Immunoassay (IRP 68/40) relative to that of the 2nd IRP of Human Pituitary FSH and LH for Bioassay (IRP 78/549) is markedly greater when estimated by in-vitro interstitial cell testosterone production (TICT) bioassay than by in-vivo bioassay, and by the 4-h ovarian ascorbate depletion (OAAD) assay than by the 4-day seminal vesicle weight gain assay. Other preparations of human LH which, like IRP 68/40, were highly purified, showed a similar spectrum of bioactivity in these assay systems and also contained a higher proportion of more basic LH isoforms than are found in crude pituitary extracts such as IRP 78/549. In an attempt to explain these differences, a comparison was made of the plasma survival in rats of the LH bioactivity (by TICT assay) of these two preparations. Contrary to expectation, their relative plasma clearance rates over a 4-h period did not account for their differing bioactivities. The plasma half-life of the LH bioactivity (with 95% confidence limits) was estimated to be 42.4 (35.3-49.5) min for IRP 68/40 and 41.3 (31.5-51.0) min for IRP 78/549. Furthermore the time-course of action in vivo of IRP 78/549 did not appear to be more prolonged than that of IRP 68/40. Thus their plasma testosterone responses during the course of these 4-h plasma clearance studies were similar, and estimates of the LH potency of IRP 68/40 relative to that of IRP 78/549 were no greater by 2-h than by 4-h OAAD assay.(ABSTRACT TRUNCATED AT 250 WORDS)

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Eleven years after developing idiopathic ovarian failure in her early twenties, a 32-year-old woman underwent in vitro fertilisation (IVF) in which her partner was the sperm donor and her own sister the oocyte donor. This treatment resulted in the delivery of a healthy girl in January 2004. However, 12 months later, she presented to her GP with left iliac fossa pain and a positive home pregnancy test.Assessment by the local gynaecology team demonstrated a serum human chorionic gonadotrophin (hCG) level varying between 190 and 260 iu/l, while an ultrasound demonstrated a 2-cm uterine mass, which was initially thought to be a fibroid. After further investigations demonstrated a rise in the hCG level, a laparoscopy and dilatation and curettage were performed.Histopathological examination demonstrated fragments of endometrium and myometrium with infiltration of the myometrium by sheets of mitotically active cells with eosinophilic cytoplasm and ovoid nuclei highly suggestive of the diagnosis of placental site trophoblastic tumour (PSTT) (Figure 1).At this point, she was referred to Charing Cross Hospital, London, one of the national centres in the UK for treatment of trophoblastic tumours. Updated investigations demonstrated the hCG level to remain elevated at 111 iu/l. A pelvic Doppler ultrasound confirmed the presence of a 3-cm mass of low vascularity, while pelvic magnetic resonance imaging and a computed tomography (CT) of the chest and abdomen did not show any evidence of distant spread.Following investigations, she was treated surgically with a hysterectomy plus bilateral salpingo-oophorectomy. The pathology confirmed the diagnosis of PSTT confined to the uterus, although malignant cells were found adjacent to the serosal surface.Fluorescent microsatellite genotyping was performed on DNA from tumour cells obtained by microdissection of formalin-fixed, paraffin-embedded sections and from blood samples from the patient, her partner and sister. The genotype of the tumour was disomic, with one allele from the partner and one from the patient's sister for five informative alleles (Table 1). No maternal alleles was identified at any informative loci.Postoperatively, the hCG level fell to normal. However, as malignant cells were present at the serosal resection surface, she received 8 weeks of adjuvant chemotherapy using the paclitaxel/etoposide paclitaxel/cisplatin regimen. 1 Following completion of chemotherapy, a repeat CT scan staging showed no evidence of disease and the hCG level was normal. At the most recent clinic visit 6 months after completing treatment, the hCG remains within the normal range and the patient is clinically well. DiscussionGestational trophoblast disease (GTD) is a rare complication of pregnancy, forming a spectrum of illness from molar pregnancy through choriocarcinoma and PSTT. Overall, in the UK, approximately 100 women require treatment with chemotherapy each year. The majority of these are identified through the UK national molar pregnancy follow-up service; however, choriocarcinoma an...

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