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K Seferiadis

Publications and source records attributed to K Seferiadis.

At least 37 records · Page 2Linked to original sources
PubMed1998

Leptin concentrations in the follicular phase of spontaneous cycles and cycles superovulated with follicle stimulating hormone.

It has been reported that oestradiol may play a role in the production of leptin from adipocytes. To investigate this relationship further, nine normally ovulating women were studied during two menstrual cycles, i.e. an untreated spontaneous cycle and a cycle treated with follicle stimulating hormone (FSH) from cycle day 2 until the day of human chorionic gonadotrophin (HCG) injection. Serum leptin values on cycle day 2 did not differ significantly between the spontaneous and the FSH cycles. In the spontaneous cycles, leptin values declined gradually and significantly up to day 7 and then increased progressively up to the day of luteinizing hormone (LH) surge onset, at which point they achieved the highest values. In the FSH cycles, serum leptin values increased gradually and significantly up to day 6, remaining stable thereafter, and were in the midfollicular phase significantly higher than in the spontaneous cycles. Significant positive correlations were found between mean values of leptin and mean values of oestradiol during the second half of the follicular phase in the spontaneous cycles and during the first half in the FSH cycles. A significant negative correlation was found between these two parameters in the spontaneous cycles during the first half of the follicular phase. Serum leptin levels were significantly higher in the midluteal than in the follicular phase in both cycles. These results demonstrate for the first time significant changes in leptin values during the follicular phase of the human menstrual cycle and a significant increase during superovulation induction with FSH. It is suggested that oestradiol may be involved in the regulation of leptin production in women.

Adult↗
PubMed1998

Luteinizing hormone response to gonadotrophin-releasing hormone in normal women undergoing ovulation induction with urinary or recombinant follicle stimulating hormone.

Oestradiol enhances pituitary sensitivity to gonadotrophin-releasing hormone (GnRH) in normal women, while in women undergoing ovulation induction the putative factor gonadotrophin surge attenuating factor (GnSAF) attenuates the response of luteinizing hormone (LH) to GnRH. To study the relationships between oestradiol and GnSAF during ovulation induction, 15 normally ovulating women were investigated in an untreated spontaneous cycle (control, first cycle), in a cycle treated with daily i.m. injections of 225 IU urinary follicle-stimulating hormone (FSH) (Metrodin HP, uFSH cycle) and in a cycle treated with daily s.c. injections of 225 IU recombinant FSH (Gonal-F, rFSH cycle). Treatment with FSH started on cycle day 2. The women during the second and third cycle were allocated to the two treatments in an alternate way. One woman who became pregnant during the first treatment cycle (rFSH) was excluded from the study. In all cycles, an i.v. injection of 10 microg GnRH was given to the women (n = 14) daily from days 2-7 as well as from the day on which the leading follicle was 14 mm in diameter (day V) until mid-cycle (n = 7). The response of LH to GnRH at 30 min (deltaLH), representing pituitary sensitivity, was calculated. In the spontaneous (control) cycles, deltaLH values increased significantly only during the late follicular phase, i.e. from day V to mid-cycle, at which time they were correlated significantly with serum oestradiol values (r = 0.554, P < 0.01). Initially during the early follicular phase in the uFSH and the rFSH cycles, deltaLH values showed a significant decline which was not related to oestradiol (increased GnSAF bioactivity). Then, deltaLH values increased significantly on cycle day 7 and further on day v with no change thereafter up to mid-cycle. On these two days, deltaLH values were correlated significantly with serum oestradiol values (r = 0.587 and r = 0.652 respectively, P < 0.05). During the pre-ovulatory period, deltaLH values in the FSH cycles were significantly lower than in the spontaneous cycles. Significantly higher serum FSH values were achieved during treatment with uFSH than rFSH. However, serum values of oestradiol, immunoreactive inhibin, and deltaLH as well as the number of follicles > or = 12 mm in diameter did not differ significantly between the two FSH preparations. These results suggest that in women undergoing ovulation induction with FSH, oestradiol enhances pituitary sensitivity to GnRH, while GnSAF exerts antagonistic effects. The rFSH used in this study (Gonal-F) was at least as effective as the uFSH preparation (Metrodin-HP) in inducing multiple follicular maturation in normally cycling women.

Adult↗
PubMed1998

Interleukins, TNF-alpha and beta-2M in patients with B cell chronic lymphocytic leukemia.

In order to investigate the possible existence of a prognostic factor for B cell chronic lymphocytic leukemia (B-CLL), we determined the serum levels of TNF-alpha, IL-1a, IL-1b, IL-2, sIL-2R, IL-6, IL-10 and beta-2M in 20 patients. We observed significant changes in sIL-2R and beta-2M levels, whereas in all stages of disease, TNF-alpha and other interleukins exhibited only mild changes. An excellent correlation between sIL-2R and beta-2M levels and disease activity wes reported. Patients with aggressive disease (Rai stages III and IV and Richter's syndrome) had increased levels. Patients who responded to therapy and with improved clinical status had decreased sIL-2R and beta-2M levels. However, patients with progressive disease and no response to therapy were associated with increased levels of sIL-2R and beta-2M. In conclusions, as serum levels of sIL-2R and beta-2M are increased in the aggressive stages of B-CLL, they may be used as reliable markers for monitoring B-CLL activity, showing response to treatment and early relapse and/or disease progression.

Adult↗
PubMed1997

Changes in gonadotrophin response to gonadotrophin releasing hormone in normal women following bilateral ovariectomy.

OBJECTIVE: Pituitary responsiveness to GnRH varies throughout the normal menstrual cycle. We have investigated whether there are differences in the ovarian mechanisms which regulate gonadotrophin secretion between the follicular and the luteal phase of the cycle. DESIGN: Normally ovulating women were studied during the first week following hysterectomy plus bilateral ovariectomy performed either in the mid- to late follicular phase (follicle size 16 mm) or in the early to midluteal phase (5 days post LH peak). The response of LH to a single dose of 10 micrograms GnRH was investigated 2 hours before the operation and every 12 hours after the operation until postoperative day 4 and every 24 hours until day 8. PATIENTS: Fourteen normally cycling premenopausal women with normal FSH (< 10 IU/l). Seven women were ovariectomized in the follicular and 7 in the luteal phase. MEASUREMENTS: Pituitary response to GnRH was calculated as the net increase in FSH (delta FSH) and LH (delta LH) at 30 minutes above the basal value. RESULTS: Basal levels of FSH and LH before the operation were significantly lower in the luteal than the follicular phase (P < 0.05), while those of oestradiol (E2) were similar. Also, similar were delta LH and delta FSH values. Serum progesterone and immunoreactive inhibin (Ir-inhibin) concentrations before the operation were higher in the luteal than the follicular phase (P < 0.05). Following the operation, serum E2, progesterone and Ir-inhibin values declined dramatically, while basal FSH and LH as well as delta FSH values showed a gradual and significant increase. The percentage increase in FSH and LH values (mean +/- SEM) on day 8 after the operation was similar in the follicular (453 +/- 99% and 118 +/- 35% respectively) and the luteal phase (480 +/- 71% and 192 +/- 45% respectively). In contrast to delta FSH, delta LH values after a temporal increase 12 hours from the operation, remained stable in the follicular phase and declined significantly in the luteal phase up to day 4. CONCLUSIONS: Basal gonadotrophin secretion during the normal menstrual cycle is predominantly under a negative ovarian effect. It is suggested that in contrast to FSH, the secretion of LH in response to GnRH is controlled by different ovarian mechanisms during the two phases of the menstrual cycle.

Adult↗
PubMed1996

A combined approach for the early detection of ovarian cancer in asymptomatic women.

The purpose of this study was to investigate the effectiveness of the combined procedure including pelvic examination and serum CA-125 determination, as a screening method for the early detection of ovarian cancer. In 2000 women over 45 years old, without any evidence of adnexal disease, pelvic examination and serum CA-125 determination were performed. When either the findings of the pelvic examination were ambiguous or positive, or the serum CA-125 level was > 35 U/ml, further investigation including ultrasonography and laparoscopy or laparotomy was done. Among 174 women with clinical findings of adnexal disease there were 15 (8.62%) who had serum CA-125 > 35 U/ml. Among 18 women with elevated serum CA-125 (> 35 U/ml) there were 15 women (83.33%) who had clinical findings of adnexal disease. In 15 women further investigation was suggestive of adnexal disease and surgical exploration revealed three cases of malignancy. One case of serious ovarian cystadenocarcinoma stage Ia, one case of borderline ovarian tumour and one case of metastatic carcinoma from the right kidney. The other 12 women had benign adnexal masses or pelvic endometriosis. In our study this combined approach had sensitivity 100%, specificity 99.70% and P.P.V. 22%. According to these data, the procedure could be a potential component of a strategy aimed to the early detection of ovarian cancer, regardless of the financial cost.

Aged↗
PubMed1996

Effect of follicle stimulating hormone or human chorionic gonadotrophin treatment on the production of gonadotrophin surge attenuating factor (GnSAF) during the luteal phase of the human menstrual cycle.

OBJECTIVE: Although there is much in-vivo evidence for the existence of a gonadotrophin surge attenuating factor (GnSAF), its source and identity remain unknown. We have studied the control of GnSAF production by FSH and hCG during the luteal phase of the cycle. DESIGN: Normally cycling women were investigated in three cycle. Starting on day 5 after the midcycle LH peak, the women received i.m. injections of placebo (1st cycle control), hCG at a dose of 750 IU per day (2nd cycle) and FSH at a dose of 225 IU per day (3rd cycle) for five consecutive days. The response of LH to a single i.v. dose of 10 microg GnRH (GnSAF bioactivity) was investigated several times during the experimental period. PATIENTS: Six normally ovulating women with long-standing unexplained infertility were studied. The women were used as their own controls during the cycle treated with placebo. MEASUREMENTS: Pituitary response to GnRH was calculated as the net increase in LH at 30 minutes (deltaLH) above the basal value. RESULTS: Serum concentrations of FSH and hCG increased significantly during the second and 3rd cycles respectively. Compared with the control cycles, deltaLH was significantly attenuated as early as 12 hours from the onset of FSH injections. In contrast, basal concentrations of oestradiol (E2) and immunoreactive inhibin started to increase 48 hours after the first injection of FSH, while progesterone values remained similar to those in the controls. During treatment with hCG, no attenuation was seen in deltaLH values, while those of E2, progesterone and inhibin showed a significant increase. CONCLUSIONS: These results demonstrate that during the luteal phase of the human menstrual cycle, FSH, but not LH, stimulates the production of gonadotrophin surge attenuating factor. It is suggested that the source of gonadotrophin surge attenuating factor at that stage of the cycle is a cohort of small follicles rather than the corpus luteum.

Adult↗
PubMed1996

Combination therapy with recombinant human erythropoietin, interferon-alpha-2b and granulocyte-macrophage colony-stimulating factor in idiopathic myelofibrosis.

Seven patients, 3 men and 4 women 48-72 years of age and suffering from idiopathic myelofibrosis were given a combination of recombinant human erythropoietin (r-hu-Epo), interferon-alpha-2b (IFN) and GM-CSF, in an attempt to treat their pancytopenia and marrow fibrosis. The dose of r-hu-Epo was 200 U/kg 3 times weekly, that of IFN was 3 x 10(6)/U 3 times weekly, and that of GM-CSF was 250 micrograms/m2/daily. The duration of therapy ranged from 3 to 6 months for r-hu-Epo and IFN and was 3 weeks for GM-CSF. The treatment regimen had a beneficial effect on all patients. The levels of hemoglobin increased in all patients but particularly in 5 (2 of whom had been dependent on red blood cell transfusions). Splenomegaly decreased significantly in 4 patients. Fibrosis in the bone marrow decreased in 2 patients. Three patients also had an increase in the number of white blood cells during the therapy with GM-CSF. We observed mild side effects in 6 of our patients. One patient had severe side effects from IFN and treatment was discontinued. In conclusion, the combination of r-hu-Epo, IFN and GM-CSF may improve the anemia (due to r-hu-Epo), increase the white blood cell count (due to GM-CSF) and reduce the marrow fibrosis (probably due to IFN) in patients with idiopathic myelofibrosis.

Aged↗
PubMed1996

Changes in pituitary response to gonadotropin-releasing hormone following bilateral ovariectomy in women treated with follicle-stimulating hormone.

Superovulation- induction in women attenuates the pituitary response to gonadotropin-releasing hormone (GnRH). The aim of this study was to assess the duration of the suppressing activity of the ovaries on the pituitary. Eighteen normally ovulating women received treatment with follicle-stimulating hormone (FSH, 225 IU/day) on cycle days 2, 3 and 4. On cycle day 4, six women underwent hysterectomy plus bilateral ovariectomy (group A), another six women underwent hysterectomy without ovariectomy (group B) and the remaining six women underwent no operation (group C). The women of group C were also investigated during a preceding untreated spontaneous cycle (group D). The response of luteinizing hormone (LH) to an intravenous injection of 10 micrograms GnRH was investigated on cycle days 2, 3, 4 (2 and 12 h after clamping of the infundibulopelvic and/or round ligaments), 5, 6 and 7 in all four groups. The response of LH to GnRH at 30 min (delta LH) was significantly attenuated as early as 12 h from the onset of FSH treatment (groups A, B and C), while estradiol and inhibin concentrations started to increase later (group C). In group C (no operation), the attenuation of delta LH values continued throughout the study period, while in groups A and B the initial attenuation was followed by a marked increase in delta LH values within 2 h from the operation. The increase in group A was twice the value in group B. Following this, delta LH values in group B were attenuated again within the next 24 h, while in group A they remained for the rest of the postoperative period significantly higher than in group B. In conclusion, it was found that the factor that mediates the suppressing effect of superovulated ovaries on the pituitary has a short-lasting (< 2 h) attenuating activity in the circulation.

Adult↗
PubMed1995

Gamma-chain heterogeneity in Greek (delta beta)zero-thalassemia.

A molecular and biochemical population study of (delta beta)zero thalassemia in central Greece is described. The molecular study was focused on the type of the deletion and the status of G gamma-XmnI polymorphism, whereas the biochemical approach was centered on the G gamma/A gamma ratio as well as the frequency of the A gamma T chain in the fetal hemoglobin of 19 delta beta-thalassemia heterozygotes and 3 homozygotes. This study includes individuals from the mountainous district of Epirus (northwestern Greece) where the trait was found to be concentrated along the river Arachthos. The Sicilian (delta beta)zero thalassemia deletion was found in all subjects tested by direct PCR. The levels for the G gamma-chain presented values ranging from 29 to 83% of the total gamma-chain content. Thirteen heterozygotes had the adult G gamma/A gamma ratio (mean G gamma: 35% +/- 10) of whom 10 were XmnI-negative (- / -), 6 had the newborn ratio (mean G gamma: 70% +/- 9) and were XmnI-positive, while homozygotes had equal amounts of G gamma and A gamma. Five of the 19 heterozygotes were A gamma T-positive with low levels of this A gamma-chain variant, suggesting an in-trans to the delta beta-thalassemia determinant production.

Adolescent↗
PubMed1994

Effect of follicle stimulating hormone treatment on the pituitary response to luteinizing hormone-releasing hormone in post-menopausal women.

To study the role of exogenous follicle stimulating hormone (FSH) in the attenuation of luteinizing hormone (LH) response to luteinizing hormone-releasing hormone (LHRH) during ovulation induction in women, 10 healthy post-menopausal women were treated with FSH (225 IU/day) for 5 days and normal saline (2 ml/day) for another 5 days. The two regimens were given consecutively in a 10 day experiment. The regimen for the first 5 days was randomly chosen and was given to the women in an alternate way. The response of LH to an i.v. injection of 10 micrograms LHRH was investigated twice on day 1 (i.e. before the onset of treatment and 12 h later) and once on days 2, 5 and 10 of the experiment (0900 h). Basal FSH and LH values before the onset of treatment on day 1 were similar in the five women who started with the saline and the five who started with the FSH regimen. Basal FSH values increased significantly during treatment with FSH, while LH and oestradiol values remained unchanged throughout the whole experiment. LH increment 30 min post-LHRH did not change significantly either during the first 24 h or during the whole experiment regardless of the starting regimen. These results demonstrate that in post-menopausal women the response of LH to LHRH is not affected by exogenous administration of FSH. It is suggested that exogenous FSH does not show activities on gonadotrophin secretion similar to those ascribed to a gonadotrophin surge attenuating factor.

Female↗
PubMed1994

Modulation of the action of gonadotrophin surge-attenuating factor by gonadotrophin-releasing hormone.

Gonadotrophin surge-attenuating factor (GnSAF) is a putative non-steroidal ovarian factor which attenuates the luteinizing hormone (LH) surge in superovulated women through the reduction of the pituitary response to gonadotrophin-releasing hormone (GnRH). The mechanism of action of GnSAF on gonadotrophin secretion was further studied by investigating six normally ovulating women in two cycles--a spontaneous and a follicle-stimulating hormone (FSH)-treated cycle. The response of the pituitary to five consecutive pulses of GnRH was investigated in late follicular phase (follicle size 15 mm) of both cycles. GnRH pulses, 10 micrograms each, were injected i.v. every 2 h and LH was measured in blood samples taken before and 30, 60 and 120 min after each pulse. FSH was injected daily at the fixed dose of 225 IU starting on cycle day 2. Peak values of LH increment occurred 30 min after each pulse. However, maximal LH increment occurred in both cycles after the second GnRH dose. In the FSH cycles the response of LH to the first three pulses was significantly attenuated compared with the spontaneous cycles, while the response to the fourth and fifth pulses was similar in the two cycles. In both cycles, LH increment 30 min post GnRH (net increase above the previous value) was similar after the fourth and fifth pulses. Serum concentrations of oestradiol and immunoreactive inhibin, although higher in the FSH cycles, remained stable throughout the GnRH experimental period in both cycles. These results demonstrate that multiple submaximal doses of GnRH can override the attenuating effect of GnSAF on LH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Estradiol↗
PubMed1994

Fetal globin stimulation during a short-term trial of erythropoietin in HbS/beta-thalassemia patients.

Six sickle cell/beta-thalassemia patients (3 males and 3 females) were treated with 500 U/kg body weight human recombinant erythropoietin (h-rEPO) along with 300 mg/day iron sulfate in two phases, for a period of 90 days. Fetal hemoglobin (HbF) was assayed every 2 weeks and the gamma-chain ratio at three successive intervals during the treatment. All patients showed a moderate to high increase in their HbF values (1.25- to 12-fold). The gamma-chain ratio, as determined by high performance liquid chromatography was found to be unaffected by the HbF increase. Two patients with the newborn gamma-chain ratio, responded faster to the h-rEPO treatment and achieved higher HbF values than the rest of the group. The h-rEPO treatment was very well tolerated and had a positive effect on the general clinical condition of all the patients.

Adolescent↗
PubMed1994

Effect of an increase in FSH on the production of gonadotrophin-surge-attenuating factor in women.

Gonadotrophin-surge-attenuating factor (GnSAF) is a putative nonsteroidal ovarian factor that is produced by FSH and that attenuates the LH surge in superovulated women. To study further the role of FSH in the production of GnSAF, 12 normally ovulating women were divided into two groups and investigated during two cycles: a cycle treated with placebo (control) and a cycle treated with FSH. In group 1 (n = 6), placebo (2 ml 0.9% normal saline) or FSH (450 iu) was injected i.m. on day 2 of the cycle (09:00 h). In group 2 (n = 6), placebo (2 ml 0.9% normal saline) or FSH (225 iu) was injected on the day (09:00 h) on which the dominant follicle was 14-15 mm in diameter, as measured by ultrasound (i.e. after the pituitary had been primed by endogenous oestrogen for several days). The response of LH over 30 min (delta LH) to an injection of 10 micrograms LHRH i.v. (bioassay for GnSAF in vivo) was investigated once a day in group 1, and 4, 8, 12 and 24 h after the injection of placebo or FSH in group 2. In group 1, delta LH was significantly attenuated 12 h after treatment with FSH compared with the control cycles, while serum oestradiol concentrations increased 24 h after the injection of FSH. The decrease in delta LH lasted for the period when the FSH concentration was increased (3 days). A significant decrease in the basal concentration of LH was correlated with the increase in the oestradiol concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Estradiol↗
PubMed1993

Autoantibodies to HMG-17 nucleosomal protein in autoimmune rheumatic diseases. Correlation with systemic lupus erythematosus clinical activity and with antibodies to double-stranded DNA.

OBJECTIVE: Previous studies have shown that serum from patients with systemic lupus erythematosus (SLE) contains antibodies directed against HMG-17, a nucleosomal nonhistone high mobility group (HMG) protein found in chromatin. The aim of the present study was to investigate any associations between the presence of antibodies to HMG-17 and clinical and serologic features of SLE. METHODS: Using porcine thymus as a source, HMG-17 was purified by Sephacryl S-200 chromatography followed by high performance liquid chromatography. An enzyme-linked immunosorbent assay utilizing the purified HMG-17 as antigen was developed and was used to evaluate sera from patients with autoimmune rheumatic diseases, for the presence of autoantibodies. RESULTS: Anti-HMG-17 antibodies were found in the serum of 34.8% of the patients with SLE, compared with 11.5% of patients with primary Sjögren's syndrome, 4.4% of patients with rheumatoid arthritis, and 4.1% of normal blood donors. Analysis of the clinical features of SLE using 2 different lupus activity indices revealed that anti-HMG-17 antibodies were more frequently found in patients with active disease. A positive correlation was also observed between anti-HMG-17 and anti-dsDNA levels, and levels of both of these autoantibodies demonstrated a negative correlation with C4. Analysis of sequentially obtained serum samples from 4 SLE patients revealed that, in 2 patients, anti-HMG-17 levels fluctuated in parallel with both disease activity and anti-dsDNA levels, and in the remaining 2, anti-HMG-17 levels fluctuated in parallel with disease activity. CONCLUSION: Antibodies to HMG-17 are found in patients with many different autoimmune rheumatic diseases, although they are more frequently observed in those with SLE. Their presence appears to be associated with lupus disease activity as well as with anti-dsDNA and C4 levels.

Adolescent↗
PubMed1993

Isolation by a new method and sequence analysis of chromosomal HMG-17 protein from porcine thymus.

Nonhistone chromosomal protein HMG-17 from porcine thymus has been isolated by extraction in boiling water, gel filtration and HPLC, and its complete primary structure (89 residues) has been determined. Peptides derived from enzymatic hydrolysis with trypsin, Staphylococcus aureus V-8 protease, Arg-C, and Glu-C proteinases were purified by HPLC and sequenced by the 4-(N,N-dimethylamino)azobenzene-4'-isothiocyanate/phenylisothiocyanate double coupling method. Porcine HMG-17 has a molecular mass of 9248 Da and a pI > 9.8. No glycosylation or methylation has been detected. The primary structure of this protein is almost identical to the sequence deduced from a cDNA clone derived from a human cell line. Porcine thymus HMG-17 differs from the human protein by only a single conservative substitution at position 64 (aspartic acid instead of glutamic acid). As in other HMG-17 proteins, the sequence is characterized by a lysine- and proline-rich central region, which has been implicated in DNA binding.

Amino Acid Sequence↗
PubMed1993

Changes in pituitary response to GnRH during the luteal-follicular transition of the human menstrual cycle.

OBJECTIVE: We studied changes in pituitary response to GnRH during the luteal-follicular transition of the human menstrual cycle. DESIGN: Normally cycling women were investigated during two consecutive menstrual cycles. In each woman, GnRH tests were performed during the two LH surges and several times during the luteal-follicular transition. Data for analysis were available in all women on days -8, -6, -4, -2, -1, 1, 2, 3, 4, 5 and 7 in relation to the onset of second menstruation (day 1). PATIENTS: Five normally ovulating parous women were studied. MEASUREMENTS: Pituitary response to GnRH was calculated as the net increase in LH and FSH at 30 minutes (delta LH and delta FSH) above the basal value. RESULTS: delta LH and delta FSH showed a similar pattern of significant changes during the luteal-follicular transition. They decreased progressively from days -8 to 1 and increased on day 2. delta LH and delta FSH then decreased on days 3 and 4 and showed a further increase on days 5 and 7. In contrast to these changes, basal FSH levels increased from days -2 to 1 and remained high up to day 5, while basal LH levels showed a trend to increase only after the onset of menses. CONCLUSIONS: These results demonstrate that the increase in basal FSH secretion during the luteal-follicular transition is GnRH independent. It is suggested that LH and FSH release under the stimulation by GnRH is regulated by a common mechanism.

Adult↗
PubMed1993

Effect of varying concentrations of follicle stimulating hormone on the production of gonadotrophin surge attenuating factor (GnSAF) in women.

OBJECTIVE: We studied the time-course of production of gonadotrophin surge attenuating factor (GnSAF) in relation to varying serum concentrations of FSH in women. DESIGN: Normally cycling women were investigated in four cycles, i.e. a spontaneous cycle treated with placebo (cycle P) and three cycles treated with three different FSH dosages (1 ampoule, cycle 1; 3 ampoules, cycle 3 and 6 ampoules, cycle 6). Placebo or FSH were given as a single i.m. injection on cycle day 2 (0900 h). The response of LH to an i.v. injection of 10 micrograms GnRH (GnSAF bioactivity) was investigated 4, 8, 12 and 24 hours after the injection of placebo or FSH. PATIENTS: Six normally ovulating women with long-standing unexplained infertility were studied. The women were used as their own controls during the cycle treated with placebo. MEASUREMENTS: Pituitary response to GnRH was calculated as the net increase in LH at 30 minutes (delta LH) above the basal value. RESULTS: Serum FSH concentrations increased after the injection of FSH in a dose dependent manner. Compared with cycle P, delta LH was significantly attenuated in cycle 3 and cycle 6 at 8, 12 and 24 hours and in cycle 1 at 12 hours after the injection of FSH. Basal concentrations of oestradiol (E2) and LH did not differ significantly among the four cycles at any point except in cycle 6 at 24 hours after the FSH injection when E2 values were significantly higher and LH values significantly lower than in cycle P. CONCLUSIONS: These results suggest that GnSAF bioactivity increases significantly as early as 8 hours from a single injection of FSH before any significant increase in serum E2 values. We conclude that in women the effect of FSH on the production of GnSAF in the early follicular phase is concentration dependent.

Dose-Response Relationship, Drug↗