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Biomedical subjects

I E Messinis

Publications and source records attributed to I E Messinis.

At least 19 recordsLinked to original sources
PubMed1999

Leptin concentrations in normal women following bilateral ovariectomy.

To study the relationships between gonadal steroids and leptin, 20 women with normal cycles were investigated during the postoperative period following a laparotomy. Fourteen women underwent bilateral ovariectomy plus total hysterectomy either in the mid- to late follicular phase (n = 7, group 1) or in the early to midluteal phase (n = 7, group 2). The remaining six of the 20 women underwent cholocystectomy in the early to midfollicular phase of the cycle and were used as controls (group 3). In all three groups, serum leptin values decreased rapidly up to post-operative day 4. Then, leptin values increased significantly only in group 3 (P < 0.05). Leptin values before and after the operation showed significant positive correlations with body mass index (BMI), oestradiol and progesterone. However, with multiple regression analysis, BMI was the only parameter significantly correlated with leptin in group 3 (days 0 and 4-7), whereas in groups 1 and 2 progesterone and BMI showed independent significant correlations with leptin (days 0 and 8, r = 0.601 and r = 0.602 respectively). These results demonstrate for the first time a significant reduction in leptin concentrations in normal women following bilateral ovariectomy. Although BMI seems to be the predominant factor, it is also suggested that oestradiol and progesterone may participate in the control of leptin production during the human menstrual cycle.

Adult↗
PubMed1999

Purification of a candidate gonadotrophin surge attenuating factor from human follicular fluid.

Gonadotrophin surge attenuating factor (GnSAF) is a new non-steroidal ovarian substance, different from inhibin, which attenuates the pre-ovulatory luteinizing hormone (LH) surge in superovulated women. Human follicular fluid (FF) was used as a source for the isolation of GnSAF, the activity of which was monitored in an in-vitro pituitary bioassay. Primary rat pituitary cells were incubated with test substances for 48 h and subsequently washed and incubated with 0.1 micromol/l gonadotrophin releasing hormone (GnRH) plus test substances for 4 h. GnSAF activity was expressed as the reduction of GnRH-induced LH secretion in the 4 h incubation. GnSAF was purified from 250 ml of FF which was heat-treated at 80 degrees C for 5 min. Heparin-sepharose chromatography, Con-A sepharose chromatography, reversed-phase high-performance liquid chromatography (HPLC) and preparative native gel electrophoresis were used for GnSAF fractionation. Using these purification steps, we have obtained an apparently homogeneous preparation that stains as a single band on sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis. GnSAF has an apparent molecular weight of 12.5 kDa and was identified by amino acid sequence (mass spectrometry) to be the C-terminal fragment of human serum albumin.

Amino Acid Sequence↗
PubMed1998

Effect of gonadotrophin-releasing hormone agonist treatment on growth hormone secretion in women with polycystic ovarian syndrome.

The suppression of the pituitary-gonadal axis by the administration of gonadotrophin-releasing hormone agonists (GnRH-a) is used occasionally as an adjunct therapy with gonadotrophins for ovulation induction in women with polycystic ovarian syndrome (PCOS). A number of recent clinical studies have suggested that women with polycystic ovaries (PCO) may have disturbances of normal growth hormone (GH) kinetics and alterations in the GH/insulin-like growth factor (IGF)-I system. The purpose of this study was to determine the effect of GnRH-a administration on GH-releasing hormone (GHRH)-stimulated GH release in women with PCOS. Eight women with PCO and six control women were studied before and after 2 months of treatment with the long acting GnRH-a triptoreline (3.75 mg monthly injections). GHRH was given as a single i.v. injection and blood samples for GH measurements were obtained at -15, 0, 30, 60, 90 and 120 min. The GH responses were expressed as the area under the curve (AUC) or the differences from the basal value (delta(max)). The GH response to GHRH (mean +/- SEM) was lower in women with PCO (AUC 114.9 +/- 43.1 versus 206.2 +/- 28.7 ng/ml/120 min, P < 0.05 and delta(max) 31.6 +/- 8.2 versus 49.4 +/- 5.8 ng/ml, P < 0.05). After treatment with the GnRH-a, the GH response to GHRH was significantly smaller than before treatment in both groups (PCO AUC 34.6 +/- 9.0 ng/ml/120 min and delta(max) 12.4 +/- 3.1 ng/ml; controls AUC 148.8 +/- 28.4 ng/ml/120 min and delta(max) 31.2 +/- 6.1 ng/ml), but the PCO group had a significantly smaller response. These data demonstrate that women with PCO have a reduced GH response to GHRH compared with normal controls and that GnRH-a administration causes a further GH reduction in both groups. Women with PCO have a greater suppression of GH response to GHRH during treatment with GnRH-a. This suggests that a different level of sensitivity in the somatotrophic axis exists in PCOS.

Adult↗
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

Circulating endothelin-3 and prolactin concentrations in healthy lactating women during the early puerperium.

OBJECTIVE: To study the association between the circulating concentrations of endothelin-3 and prolactin in the early puerperium. DESIGN: Prospective clinical study, including twenty-five healthy puerperal women breast-feeding their healthy full-term infants. METHODS: Venous blood was drawn on day 1 and 4 post partum, and plasma endothelin-3 and serum prolactin were determined. RESULTS: Circulating endothelin-3 and prolactin levels on day 4 did not differ significantly from the corresponding levels on day 1. However, a significant negative correlation was found on day 4 between endothelin-3 and prolactin values (r = -0.688, P < 0.001) and an even stronger negative association existed between the net change in endothelin-3 from days 1 to 4 and the corresponding change in prolactin values (r = -0.732, P < 0.001). CONCLUSIONS: On the fourth day post partum, lactating healthy women show negative correlation between circulating endothelin-3 and prolactin levels. Whether this indicates a role for endothelin-3 in the control of prolactin secretion in the post partum period remains to be clarified.

Endothelin-3↗
PubMed1997

Effect of mifepristone on folliculogenesis in women treated with recombinant FSH.

OBJECTIVE: To study the mechanism through which mifepristone interrupts folliculogenesis. DESIGN: Normally ovulating women undergoing donor intrauterine insemination (IUI) treatment were investigated during two menstrual cycles treated with gonadotrophins. In the first cycle (FSH cycle), the women were given 150 IU recombinant FSH (rFSH) s.c. on days 2, 4, 6, 8 and daily thereafter until the administration of hCG. During the second cycle (FSH + mifepristone cycle), the women received rFSH as above plus mifepristone tablets at a dose of 50 mg/day from cycle day 2 until the hCG injection. IUI was performed only in the FSH cycles. PATIENTS: Eleven normally ovulating women were studied. The women were used as their own controls during the cycle treated with rFSH only. RESULTS: Two women became pregnant during the FSH cycle and, therefore, data for comparison between the two cycles were available in nine women. In both cycles, only one follicle reached the preovulatory stage. However, during treatment with FSH + mifepristone the growth of the dominant follicle was temporarily arrested after day 8 of the cycle and ovulation was postponed by 2 days on average. Serum FSH values increased significantly in both cycles only during the daily administration of rFSH, i.e. towards the end of the experimental period when a normal growth of the follicle was re-established. On the day of hCG injection, an endogenous LH surge had already started in six of the nine cycles treated with FSH (67%) but in none of the FSH + mifepristone cycles despite the preovulatory oestradiol (E2) levels. Endometrial thickness during the follicular phase and serum E2 and progesterone concentrations during the luteal phase, although in the normal limits, were significantly lower in the FSH + mifepristone than in the FSH cycles. CONCLUSIONS: These results suggest that mifepristone arrests follicular development at a stage beyond the recruitment-selection point by delaying the growth of the dominant follicle. This is probably achieved through an effect of mifepristone on the ovary where it reduces the sensitivity of the selected follicle to FSH. Mifepristone may have a potential application for the inhibition of the LH surge in superovulation induction programmes.

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↗
PubMed1997

Oestrogen receptor gene polymorphisms and ovarian stimulation for in-vitro fertilization.

Experimental evidence has shown that mice lacking the oestrogen receptor (ESR) gene are infertile with cystic ovaries and follicular arrest. In humans, several polymorphisms and mutations in the ESR gene have been identified. In this study we have analysed a common PvuII and a rare BstUI polymorphism in the ESR gene. Analysis was carried out on DNA samples from women undergoing ovarian stimulation for in-vitro fertilization (IVF) and embryo transfer and controls having at least one pregnancy. Comparisons were done between the three PvuII genotypes, concerning the mean numbers of follicles and oocytes and the mean ratios of follicles to oocytes harvested in two consecutive cycles. Significantly lower ratios were identified in the group lacking the PvuII polymorphism, compared with the groups with heterozygous or homozygous PvuII polymorphisms (P > 0.05 and P > 0.01 respectively). The rare haplotype having both PvuII and BstUI restriction sites on one chromosome was present only in the IVF group. Pregnancies from IVF were significantly rarer in patients who were homozygous for the PvuII polymorphism (P > 0.05). Our results suggest that genetic variability in the ESR has a role in the quality of the ovarian follicles as judged by the ovarian response to stimulation and may also affect implantation.

Adult↗
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

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

The follicle-stimulating hormone threshold level for follicle maturation in superovulated cycles.

OBJECTIVE: To compare the FSH threshold level for follicle growth up to the preovulatory stage between superovulated and natural cycles. DESIGN: Normally cycling women were investigated during an untreated spontaneous cycle (control) and three cycles treated with FSH. SETTING: Infertility clinic in a university hospital. PATIENTS: Thirteen normally ovulating women with unexplained infertility. INTERVENTIONS: Follicle-stimulating hormone was injected at the single dose of six ampules on cycle day 2 without extra FSH (FSH + 0 cycle) or with extra FSH from cycle day 4 onward at the daily dose of either one ampule (FSH + 1 cycle) or two ampules (FSH + 2 cycle). MAIN OUTCOME MEASURES: Serum FSH and E2 during the follicular phase. Number of follicles and growth rate by ultrasound. RESULTS: Multiple follicular development occurred in all FSH treated cycles. In these cycles the growth rate of the first (dominant) follicle was similar to that in the control cycles. In the presence of physiological concentrations of FSH (control and FSH + 0 cycles), only one follicle was > 15 mm at midcycle. When serum FSH values increased (FSH + 1 and FSH + 2 cycles), the growth rate of the second and third in order follicles and subsequently the number of the preovulatory follicles (> 15 mm) increased in proportion to the FSH increment. CONCLUSIONS: Follicles recruited by exogenous FSH in the early follicular phase of the cycle require supraphysiological concentrations of FSH throughout the follicular phase to become preovulatory. The extra FSH acts through an increase in the growth rate of these follicles.

Estradiol↗
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

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↗
PubMed1994

Circulating gonadotrophin surge-attenuating factor from superovulated women suppresses in vitro gonadotrophin-releasing hormone self-priming.

A perifusion system based on ovine pituitary tissue explants was used to investigate the effects of follicular fluid (hFF) and serum from superovulated women on pituitary responsiveness to gonadotrophin-releasing hormone (GnRH). The specific aims of the study were to determine both if gonadotrophin surge-attenuating factor (GnSAF) bioactivity is present in the peripheral circulation as well as in the follicles of superovulated women and if GnSAF suppresses GnRH self-priming in vitro. Two pulses of GnRH, 1 h apart, produced marked peaks in LH secreted from control chambers, with GnRH self-priming evident in the significant difference between the first (134.4 +/- 1.7 - 232.1 +/- 24.0% of basal secretion) and second (183.9 +/- 15.8 - 313.9 +/- 14.0% of basal secretion) LH peaks. Both follicular fluid and serum pooled from two different groups of women produced marked suppression of the first (unprimed) and second (primed) LH peaks. The hFF reduced the first LH peak to 69.6 +/- 7.8 and 60.2 +/- 9.7% and the second LH peak to 57.4 +/- 6.7 and 42.6 +/- 6.5% of control LH secretion. Overall, the serum reduced the first and second LH peaks to 76.8 +/- 4.2 and 62.9 +/- 3.6% of control respectively. These results demonstrated that GnSAF bioactivity suppresses GnRH self-priming, and is present in both the peripheral circulation and hFF. The same material administered to dispersed ovine pituitary monolayers produced similar marked suppression of GnRH-induced LH secretion, with approximately 50-fold less GnSAF bioactivity in serum compared with hFF. Combined doses of oestradiol and progesterone, or hFF from large follicles containing little GnSAF, produced stimulation of GnRH-induced LH secretion and GnRH self-priming (second peaks 78.1 +/- 38.9 and 27.4 +/- 15.7% respectively higher than first peaks). Thus, in conclusion, GnSAF in hFF and serum markedly attenuated both unprimed and primed pituitary response to GnRH, virtually abolishing the GnRH self-priming effect.

Animals↗