24-hour profiles of salivary progesterone.

OBJECTIVES: To assess whether the known pulsatility of P secretion by the corpus luteum, which is detected in blood by P measurements, translates into fluctuations of saliva P concentrations, and to determine how well saliva P measurements reflect plasma P concentration. A second objective was to see whether there is a window in the luteal phase, where P secretion has reached its maximum capacity, but the amplitude is not very accentuated, which would be an ideal time to measure P. DESIGN: Twenty-one ovulatory women were randomly assigned to be studied on day 5, 7, or 8 after the luteinizing hormone surge. Blood samples were drawn every 20 minutes, and saliva samples were obtained hourly over a 24-hour period. Comparison between saliva plasma P was performed, and pulse analysis of plasma P was done. RESULTS: The percent variation of saliva P concentration over a 24-hour period was much higher when compared with the percent variation of plasma P concentration over the same time period (saliva P: 149%; plasma P: 107%). Also, the ratio of saliva to plasma P varied significantly between individuals (range: 0.0050 to 0.0148). A single plasma P concentration (8:00 A.M.) correlated better with the 24-hour mean plasma concentration than the respective single saliva value or the mean of two or three saliva samples (8:00 A.M. and 12:00 P.M.; 8:00 A.M., 12:00 P.M., and 8:00 P.M.). Plasma pulse frequency, mean pulse interval, pulse width, pulse amplitude, and 24-hour mean P level did not differ between the 3 study days. CONCLUSIONS: A single plasma P determination reflects more accurately 24-hour P secretion than repeated saliva P samples measured in the same individual. We could not identify a window in the luteal phase when P measurements are more representative of corpus luteum function.

Sex steroids do not alter melatonin secretion in the human.

It is unclear whether sex steroids influence melatonin secretion in the human. In an attempt to find an answer to this important question 36 women within an age range of 19 to 40 years were studied within a 3-month period under the following conditions: natural menstrual cycle, ovulation induction with gonadotrophins, early pregnancy, and intake of monophasic or triphasic oral contraceptives. Except in the case of pregnancy, repeated measurements in the same individual were done because of the well-known large inter-individual variations in melatonin secretion. Melatonin concentration was measured in plasma samples obtained at 4-hourly intervals in a 24 h period and < 200 lux for all subjects studied. No consistent change in melatonin blood concentrations was demonstrated in response to the varying endogenous or exogenous concentrations of sex steroids. These observations suggest that circadian melatonin secretion is not significantly modulated by sex steroids.

PIP: The pineal gland hormone, melatonin, has been increasingly thought to play a significant role in the ovarian cycle. Though the evidence is unclear, some research suggests a pineal gland-ovary connection based on melatonin production during different phases in the ovarian cycle. This article reports the findings of a study on the effects of endogenous and exogenous sex steroids on melatonin secretion. 36 German women were studied over a 3-month summer period. This timing was intended to minimize the effects of seasonal influences on the women. Blood was taken every 4 hours (a total of 7 blood samples per day). Four groups were studied: women with natural menstrual cycles; 10-week pregnant women; women being treated with human menopausal/human chorionic gonadotropin; and women using phasic oral contraceptives. Melatonin was extracted from blood by using Bond Elut reverse-phase C18 columns. Statistical analysis included normal distribution, non-parametric analysis, and standard statistical analysis methods. No consistent change in melatonin blood levels was found in response to the varying endogenous and exogenous sex steroid levels. These findings suggest that circadian melatonin secretion is not modulated by sex steroids in a significant way.

Laparoscopic electrocoagulation of the ovarian surface in infertile patients with polycystic ovarian disease.

OBJECTIVE: To assess the endocrinologic and clinical outcome after laparoscopic ovarian electrocautery because of polycystic reaction to ovarian stimulation in anovulatory infertility patients. DESIGN: Between 1986 and 1989, 133 patients with polycystic ovarian disease underwent laparoscopic electrocoagulation of the ovarian surface in an outpatient clinic after conventional ovarian stimulation had led to polycystic reaction. SETTING: All patients were referred to our outpatient clinic affiliated with the university hospital. RESULTS: The reduction of androgen levels and normalization of cycle length were highly significant. The overall pregnancy rate was 70% (73 of 104), ranging from 27% in smokers to 94% in nonsmoking couples. In 26 second-look operations de novo adhesions were found in 26.9% of the patients. CONCLUSION: Laparoscopic coagulation of the ovarian surface is an effective tool to reduce elevated androgen levels and to improve the intraovarian mechanism of selecting a dominant follicle. A postoperative complication may be adhesion formation.

A direct immunoradiometric assay for human plasma prorenin: concentrations in cycling women and in women taking oral contraceptives.

Two synthetic penta deca peptides corresponding to the N-terminal portion (amino acid sequence 1-15) and the C-terminal portion (sequence 32-46) of the pro moiety of the human prorenin (PR) molecule were coupled to BSA and used as antigens to generate antibodies against PR. In a RIA system using the 125I-labeled peptide as tracer, it could be shown that antibodies against peptide 32-46 bound the peptide and the native PR in the follicular fluid (FF) to a similar degree, whereas antibodies generated against peptide 1-15 did not specifically recognize native PR. The specificity of the PR-(32-46) antibodies for PR was demonstrated by comparative measurements of PR by RIA and by an indirect procedure (involving trypsin treatment of PR) in different individual FF samples, plasma samples, and fractions of FF obtained by gel filtration or immunoaffinity chromatography. Normal plasma PR levels could not be measured by RIA, since they were below the detection limit of the assay (0.5 micrograms PR/L approximately 10 pmol/L). For measurement of the low PR levels in plasma, a sensitive direct immunoradiometric assay with a detection limit of 0.1 fmol PR/tube was developed. It was based on the combined action of a commercially available solid phase renin antibody and the affinity-purified and 125I-labeled PR-(32-46) antibody. The measurement of 35 individual plasma samples with different PR concentrations showed an excellent correlation (r = 0.99) between the new direct and the conventional indirect assays. The direct assay of PR concentrations in plasma of healthy women during the length of a menstrual cycle resulted in a biphasic pattern of PR concentrations, with peak levels (approximately 3-fold increase) at the time of the LH surge. The intake of monophasic and triphasic contraceptives caused a suppression of normal PR concentrations (96.9 +/- 34 ng/L; early follicular phase; n = 12) by 39% and 25%, respectively, which was also observed in the pill-free phase of the artificial cycle.

PIP: This paper studies the effects of different oral contraceptives on plasma prorenin (PR) levels in women as determined by a direct immunoradiometric assay (IRMA). 3 healthy and normally cycling women, aged 22, 30, and 37, volunteered for venipuncture every second day of one complete menstrual cycle. 18 healthy women taking oral contraceptives were studied for the effects of oral contraception on plasma PR concentrations. Results of this study showed that in a renin-angiotensin (RIA) system, using the I-labeled peptide, antibodies against peptide 32-46 bound the peptide and the native PR in the follicular fluid (FF) to a similar degree, while antibodies generated against peptide 1-15 did not recognize native PR. The absolute PR levels measured by the direct assay were approximately 20% lower than in the indirect assay, although both assay procedures indicate the same molecular measurement. The measurement of the different PR concentrations of the 35 individual plasma samples indicates an excellent correlation (r = 0.99) between the new direct and the conventional indirect assays. Sequential changes in the plasma PR levels of healthy women demonstrate that PR in the circulation was mainly due to ovarian origin. Lastly, PR concentration was significantly lower at any time during the artificial cycle than in the early follicular phase of spontaneous cycles. In conclusion, this PR IRMA is believed to be superior to the conventional indirect procedures.

[Results of treatment with surface cauterization of polycystic ovaries in sterility patients]. / Behandlungsergebnisse mit der Oberflächen-kauterisierung polyzystischer Ovarien bei Sterilitätspatientinnen.

In 39 women with polycystic ovaries (PCO) and a history of sterility, laparoscopic electrocautery of the surface of the ovaries was performed by a technique adapted from Gjoennaess (1984). Previous hormonal treatment with clomiphene and/or human menopausal gonadotropins had been unsuccessful in these patients, whilst 23 of them (59%) conceived within one year after surgery. Electrocautery was followed by a decrease of mean testosterone levels from 0.95 +/- 0.064 ng/ml to 0.48 +/- 0.041 ng/ml and a similar decline of dehydroepiandrosterone sulfate from 2.9 +/- 0.136 g/ml to 1.6 +/- 0.165 g/ml respectively. Laparoscopic ovarian electrocautery is however associated with the risk of postoperative adhesion formation. Therefore we advise this form of surgery only, when hormonal therapy failed or if it presents an unacceptable high risk of hyperstimulation or a multiple pregnancy.

Glucocorticoid-induced lymphoma cell death: the good and the evil.

Glucocorticoid hormones and their synthetic derivatives are widely used in therapy due to their strong anti-inflammatory and immunosuppressive potential. While the molecular basis of the anti-inflammatory action is to date at least partially understood, knowledge regarding the mechanism underlying glucocorticoid effects on the immune system is rather fragmentary. The immunosuppression could be attributed to at least two distinct processes: inhibition of the production of growth mediators and glucocorticoid-induced cell death. The mechanism of glucocorticoid-induced cell death can be divided into two steps, a reversible growth inhibition and cell lysis. The first step is characterized by many metabolic alterations typical of the catabolic potential of corticosteroids. After a delay of several hours activation of an endonuclease appears to initiate the lytic phase. By the action of this endonuclease the DNA is fragmented. In opposition to the chromatin damage, poly(ADP-ribosyl)ation is activated in order to stabilize the chromatin structure until the antagonistic potential is exhausted and the cells die. Therefore it can be speculated that the lethal event in glucocorticoid-induced cell death is a destruction of the regular chromatin structure.

Glucocorticoid-induced cell death and poly[adenosine diphosphate(ADP)-ribosyl]ation: increased toxicity of dexamethasone on mouse S49.1 lymphoma cells with the poly(ADP-ribosyl)ation inhibitor benzamide.

Treatment of S49.1 mouse lymphoma cells with the synthetic glucocorticoid dexamethasone resulted in a delayed cell death. During the 24-h latency period, DNA, RNA, and protein synthesis fell to about 50%, 60%, and 30% of control values, respectively, without a change in ATP levels, the latter suggesting cellular integrity. The onset of cellular suicide was characterized by the occurrence of DNA strand breaks, finally leading to the total digestion of internucleosomal DNA. Concomitant with the appearance of DNA fragmentation, poly(ADP-ribosyl)ation was activated, a process probably involved in DNA repair. Activation of poly(ADP-ribose)synthetase was paralleled by a fall in the level of the substrate NAD. An antagonistic role of poly(ADP-ribosyl)ation in glucocorticoid-induced cell death was suggested by the observation that low concentrations of the potent poly(ADP-ribose)synthetase inhibitor benzamide enhanced the toxicity of dexamethasone several-fold and shortened the interval between steroid addition and the onset of cell death. In addition, the fall in NAD was prevented by benzamide. The antagonistic function of poly(ADP-ribosyl)ation in glucocorticoid-induced cell death is, therefore, comparable to the role of the poly(ADP-ribose)synthetase in cells treated with alkylating agents, suggesting involvement of a DNA repair phenomenon in opposition to the mechanism of glucocorticoid-induced cell death.