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Endometriosis: Harmful survival of an ectopic tissue

Endometriosis results from implantation of endometrial tissue outside the uterine cavity. Endometriosis might remain asymptomatic and discovered accidentally. However, it may cause symptoms, which include chronic pelvic pain, bleeding, infertility, and increases susceptibility to development of adenocarcinoma. The most prevailing hypothesis is that endometriosis results from implantation of endometrial tissue that gains access to peritoneal cavity by retrograde flow during menstruation. The factors contributing to the establishment and persistence of the endometriotic lesions (plaques) most probably include abnormalities of the genital tract, genetic predisposition, hormonal imbalance, altered immune surveillance, inflammatory response and abnormal regulation of the endometrial cells. The mediators that contribute to survival and progression of endometriosis are likely involved in the development of the symptoms of this process. Genomic studies have started to delineate the wide array of mediators involved and the complex genetic background required in the development of endometriosis. This review summarizes our current knowledge regarding the pathogenesis of endometriosis, including progress made with transgenic animals, and a clinical perspective on the diagnosis and management of this common process.

The effect of catecholamines, acetylcholine and histamine on progesterone release by human granulosa cells in a granulosa cell superfusion system

There are experimental data demonstrating the presence and actions of various neurotransmitters in the ovary, thus supporting the view that they might play a role in intraovarian regulatory mechanisms, although their exact function in the regulation of ovarian hormone secretion is unclear. The objective of the present study was to investigate the direct action of catecholamines, acetylcholine and histamine on progesterone secretion of human granulosa cells in a superfused cell system. Human granulosa cells were isolated from preovulatory follicular fluid using a Percoll gradient centrifugation method. Approximately 2 × 106 cells were mixed with Sephadex G-10 and were transferred into two chambers of the superfusion apparatus. The system was perfused with a culture medium and test materials were added to the system at a dose of 100 pmol/ml. The progesterone concentration of samples was measured using an 125I radioimmunoassay. Administration of epinephrine (adrenaline), norepinephrine (noradrenaline), dopamine and histamine had no effect on progesterone release. However, acetylcholine produced a significant progesterone release, which could be blocked by atropine. The observed effect of acetylcholine on progesterone release of superfused human granulosa cells may reflect a physiological role of acetylcholine in the regulation of granulosa cell function during the menstrual cycle.

The effect of histamine on progesterone and estradiol secretion of human granulosa cells in serum-free culture.

The aim of this study was to explore the direct action of histamine on progesterone and estradiol secretion of human granulosa cells cultured in serum-free medium. Human granulosa cells were isolated from preovulatory follicular fluid aspirated from 17 women (32 +/- 3 years old, mean +/- SD) undergoing in vitro fertilization treatment at the University Womens Hospital of Tübingen. Progesterone and estradiol production was measured in the presence and absence of histamine, terfenadine or cimetidine using radioimmunoassays. Statistical analysis of the data was performed by analysis of variance and Newmann-Keul tests. Histamine stimulated a dose-related increase in estradiol secretion with a maximal stimulatory effect at 10(-3) mol/l. This response was blocked specifically by the H1-receptor antagonist terfenadine. Progesterone production in response to histamine stimulation was independent of dose at the limit of significance. The specific H2-receptor antagonist cimetidine did not block the stimulatory effect of histamine. We suggest that histamine has a direct stimulatory effect on steroid production of granulosa cells mediated via the H1-receptor. This effect may have a physiological role in the regulation of granulosa cell function during the menstrual cycle.

Cholinergic Stimulation of Progesterone and Estradiol Secretion by Human Granulosa Cells Cultured in Serum-Free Medium

Cholinergic effects on hormone secretion by human granulosa cells (GCs) are not well characterized. The aim of this study was to explore the direct action of acetylcholine and carbachol on progesterone and estradiol secretion of human GCs cultured in serum-free medium. Granulosa cells were obtained from 26 women undergoing in vitro fertilization and embryo transfer. Progesterone and estradiol production was measured in the presence and absence of acetylcholine, carbachol, or atropine using radioimmunoassays; statistical analysis of the data was performed by ANOVA. Acetylcholine significantly stimulated progesterone secretion by GCs in a dose-related manner. Estradiol secretion was also stimulated by acetylcholine, but this effect did not show dose dependency. Carbachol showed a similar stimulatory effect, but to a lower degree; both effects can be blocked by acetylcholine. The results suggest that cholinergic action on steroid production by human GCs is mediated through the muscarinic route, and cholinergic neurotransmission may have a physiological significance in the intra-ovarian regulatory pathways.

Serotonin may alter the pattern of gonadotropin-induced progesterone release of human granulosa cells in superfusion system

Serotonin plays a hormonal function in several nonneuronal peripheral tissues, such as the ovaries. Our aim was to investigate whether there is a modulatory action of serotonin on gonadotropin-induced steroid secretion of human granulosa cells. In granulosa cell culture, serotonin was administered alone or in combination with luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Also, granulosa cells were transferred into a dynamic superfusion apparatus and challenged by FSH and LH alone or along with serotonin. Estradiol and progesterone concentrations of samples were measured by radioimmunoassay. As expected, administration of FSH, LH, and serotonin alone resulted in a significant estradiol and progesterone release in cell culture, as well as a significant increase in progesterone release in dynamic superfusion system. In cell culture, co-administration of serotonin with gonadotropins had no additive effect on gonadotropin-induced secretion of progesterone, while it further augmented that of estradiol. In superfusion system, when gonadotropins were added along with serotonin, the increase in progesterone release was markedly less, while peaks of hormone response were remarkably prolonged compared to challenges by LH and FSH alone. The observed effects of serotonin on gonadotropin-induced steroid release of granulosa cells may reveal further details about the regulation of granulosa cell function.

Platelets in pregnancy induced hypertension

have used the graph over the years would ever go back to the blind guesswork of pre-SF days. One of the commonest objections to using the graph is that it will increase interference and the caesarean section rate. Our section rate for many years was 5% and has never gone above lo%! But the graph has many other uses; the early diagnosis of twins, the detection of polyhydramnios, the usefulness in estimating fatal size in breech and cephalo-pelvic disproportion and the indication of fetal abnormality as in anencephaly when S-F height measurement and dates seem to be inconsistent. Also, the estimation of gestation when dates are not known or are clearly wrong, these problems are our daily bread and butter. What seems most to deter Western obstetricians from using the SF graph is the ready availability of high-tech methods for assessing fetal well-being. It must be remembered that most of the world’s women are not looked after by obstetric teams with all the latest aids to hand, but are, if they are lucky, looked after by general doctors and midwives, who may have little or no interest or experience in obstetrics. If these doctors come out to Africa thinking that without high-tech machines there is nothing they can do to assess pregnant women, how can we ever reduce the appalling statistics? They need every assistance in making the best of a bad job and for experts to argue about what are significant statistics while babies are dying in thousands is contributing nothing to solving Third World problems. Western centres of excellence have as great a responsibility to mothers in the Third World as they have to their own patients. Failure to use the partogram is another example. The partogram is still not being used everywhere in the Third World because of the ‘we can take it or leave it’ attitude of obstetricians in the West. The Third World will only follow if they lead. What you have to do is imagine yourself in a rural centre with only your eyes, ears and hands to help you and see what you make of your patient’s condition then! We desperately need you to give the lead. Please don’t let us down. Ian Kennedy Bamalete Lutheran Hospital Box 6 Ramotswa Botswana

Laparoscopic management of ovarian cysts in a Hungarian county hospital.

Laparoscopic management of ovarian cysts in a Hungarian county hospital Dear Sir, We read with special interest, the paper by Chapron et al. (1998), about the diagnostic methods in the management of ovarian cysts, with special reference to the application of frozen sections. In our practice, a high portion of adnexal masses is managed by laparoscopy. Consecutive steps of the diagnostic approach comprise bimanual pelvic palpation, transvaginal ultrasound, CA-125 antigen value and diagnostic laparoscopy. Cases suspected of malignancy are managed by laparotomy. These include immobile masses that have nodular surface, non-homogeneous echo-structure on ultrasound scan with solid parts or endovegetation, cases with CA-125 concentrations of Ͼ35 µg/ml and masses assessed by laparoscopy to have abnormal vessels and/or uneven rough capsular surface. We do not routinely consider cystic masses, a priori, to be malignant if they are detected in menopause, are bilateral or are Ͼ5 cm in diameter. We have attempted laparoscopic cystectomy or adnexectomy with success in several of those cases as well. we carried out laparoscopy due to cystic adnexal mass in 39 cases. In seven cases, we returned to laparotomy and or minilaparotomy because of bowel adhesions and/or adherence. In 32 cases, the cysts were removed via laparoscopy; histological tests demonstrated benign changes in all cases. One endometriosis, eight parovarial cysts, and 32 simplex cyst were diagnosed (both cyst types were present in one patient at the same time). No frozen sections were made. Although our numbers are small, we conclude that, even with wider criteria of benignity, malignant masses did not occur. (1994) Laparoscopic diagnosis of adnexal cystic masses: a 12-year experience with long-term follow-up. management of ovarian cysts: is there a place for frozen section diagnosis? The risk of malignancy with an apparently simple adnexal cyst on ultrasound. Arch. It was with considerable interest that we read the comments by Varga et al. (1998) following the publication of our paper on the place of frozen section in the laparoscopic management of organic ovarian cysts (Chapron et al., 1998). We entirely agree with Varga et al., when they underline that the meno-pausal status of the patient, or the size or bilateral character of the cyst, or the heterogeneous appearance of the adnexal mass at ultrasound, or a raised concentration of CA-125 are insufficient grounds to indicate malignacy for an ovarian mass. Taken separately, none of these parameters is a formal indication to carry out laparotomy. In daily …

Influence of serotonin on progesterone and estradiol secretion of cultured human granulosa cells**Supported by the Alexander von Humboldt Foundation (AvH), Bonn, Germany.

OBJECTIVE To explore the direct action of serotonin on progesterone (P) and estradiol (E2) secretion of human granulosa cells cultured in serum-free medium. DESIGN Progesterone and E2 production was measured in the presence and absence of serotonin, propranolol, or cycloheximide using radioimmunoassays; statistical analysis of the data was performed by ANOVA. SETTING In vitro fertilization and embryo transfer (IVF-ET) for infertility treatment at the University Womens Hospital, University of Tübingen, Germany. PATIENTS, PARTICIPANTS Fourteen women, 30 +/- 3 years old, undergoing IVF-ET. RESULTS Serotonin stimulated a dose-related increase in P secretion with a maximal stimulatory effect at 10(-4) M. This response was blocked specifically by the beta-receptor antagonist propranolol (10(-4) M). Estradiol secretion in response to serotonin was dose-independent stimulation, which was highest at 10(-6) M and was inhibited by 10(-4) M propranolol. The protein synthesis inhibitor cycloheximide markedly reduced the stimulatory effect of serotonin on P secretion. Estradiol production in the presence of cycloheximide was significantly reduced; serotonin had no stimulatory effect under these conditions. CONCLUSION Serotonin may have a physiological role in the corpus hemorrhagicum, when luteinization is initiated.