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Biomedical subjects

I E Messinis

Publications and source records attributed to I E Messinis.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1993

The ovarian modulation of gonadotrophin releasing hormone-induced luteinizing hormone secretion in women.

Ovine pituitary cell culture and perfusion bioassays were used to investigate gonadotrophin surge-attenuating factor (GnSAF) bioactivity in vitro. GnSAF is present in steroid-free human follicular fluid (HFF) from superovulated women and specifically attenuates gonadotrophin releasing hormone (GnRH)-induced luteinizing hormone (LH) secretion. HFF produced dose-dependent suppression of GnRH-induced LH and basal FSH secretion, the former reflecting GnSAF bioactivity, the latter inhibin bioactivity. Heparin-Sepharose chromatography of HFF removed inhibin bioactivity, but not GnSAF bioactivity, indicating that these are distinct entities. Ultrafiltration of HFF suggests that GnSAF has a bioactive form of 10-30 kDa. Ovine pituitary perfusion demonstrated that GnSAF bioactivity in HFF is matched in the serum of superovulated and pregnant women. In addition, HFF and serum suppress both the initial and reserve pools of GnRH-induced LH secretion and greatly reduce the self-priming effect of GnRH in ovine pituitary tissue perfusion. In-vitro and in-vivo GnSAF bioactivity is consistent with a role for GnSAF in the gonadal feedback regulation of pituitary response to GnRH.

Animals↗
PubMed1993

Effects of gonadotrophin surge-attenuating factor on the two pools of gonadotrophin-releasing hormone-induced luteinizing hormone secretion in vitro.

In order to study the in-vitro mechanism of action of gonadotrophin surge-attenuating factor (GnSAF), ovine pituitary monolayers were incubated for 48 h either with steroid-free follicular fluid from women in whom ovulation had been induced or oestradiol or progesterone. Monolayers were also incubated with 10-30 and > 30 kDa follicular fluid fractions. The effect of these preparations on gonadotrophin-releasing hormone (GnRH)-induced luteinizing hormone (LH) secretion was then determined by incubation with GnRH for between 15 and 240 min. Incubation with steroid-free follicular fluid resulted in the significant attenuation of both the acutely releasable LH pool (LH 54.3 +/- 3.0% of control secretion at 15 min of GnRH incubation) and the reserve LH pool (LH 36.8 +/- 1.6% of control secretion at 240 min GnRH incubation). The 10-30 kDa follicular fluid fraction had similar effects while the > 30 kDa follicular fluid fraction significantly stimulated GnRH-induced LH secretion, with concentrations up to 134.0 +/- 8.6% of controls. Oestradiol or progesterone at doses of 1000 nmol/l/well did not significantly reduce any aspect of GnRH-induced LH secretion (never < 95.1 +/- 15.1% of controls). These results demonstrate that GnSAF markedly attenuates both the acutely releasable and reserve pools of GnRH-induced LH secretion. Inhibin, oestradiol and progesterone are not responsible for the marked attenuation of either the initial or reserve pools of GnRH-induced LH secretion.

Animals↗
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↗
PubMed1993

Activity of gonadotrophin surge-attenuating factor during the luteal phase in superovulated women.

Gonadotrophin surge-attenuating factor (GnSAF) is a putative nonsteroidal ovarian factor that attenuates the luteinizing hormone (LH) surge in superovulated women. GnSAF bioactivity was studied during the luteal phase by investigating six normally ovulating women in two cycles--a spontaneous and a follicle-stimulating hormone (FSH)-treated cycle. In both cycles, the pituitary response to an acute intravenous injection (10 micrograms) of luteinizing-hormone-releasing hormone (LHRH) was investigated in late follicular (follicle size 16 mm), early luteal (day 5 after human chorionic gonadotrophin, hCG), midluteal (day 9 after hCG) and late luteal phase (day 12 or 13 after hCG). FSH was injected daily at the dose of 225 iu on cycle days 2, 3 and 4, and 150 iu thereafter. The increase in LH and FSH (mean +/- SEM) 30 min after LHRH in the spontaneous cycles decreased significantly from early to late luteal phase and remained unchanged in the FSH-treated cycles. Increases in LH and FSH 30 min after LHRH were significantly attenuated in the FSH-treated compared with the spontaneous cycles in late follicular and luteal phases. Serum oestradiol and progesterone concentrations were significantly higher in the FSH than in the spontaneous cycles only in early, but not in mid- and late luteal phase. The pattern of serum oestradiol and progesterone changes during the luteal phase did not correlate with the increases in LH and FSH 30 min after hCG both in the spontaneous and the FSH cycles. These results suggest that GnSAF bioactivity is high during the luteal phase of superovulated cycles.

Estradiol↗
PubMed1992

Positive feedback effect of oestradiol in superovulated women.

To investigate the mechanism of blockage of the luteinizing hormone (LH) surge in superovulated women, six normally ovulating women were studied in three cycles: a spontaneous cycle treated with exogenous oestrogen (oestradiol benzoate cycle), a cycle treated with follicle stimulating hormone (FSH; 225 IU/day; FSH cycle) and a cycle treated with FSH plus exogenous oestrogen (FSH + oestradiol benzoate cycle). Oestradiol benzoate was injected i.m. on cycle days 4 (0800 and 2000 h), 5 (0800 h) and 6 (0800 h) at doses of 0.5, 1.0, 2.0 and 2.5 mg respectively to achieve supraphysiological levels of serum oestradiol. Exogenous oestrogen (supraphysiological oestradiol levels) induced an LH surge in all six women in the oestradiol benzoate cycles, but failed to stimulate an LH surge in three of the six patients during treatment with FSH. In three patients treated with FSH, an LH surge was stimulated both by supraphysiological (FSH + oestradiol benzoate cycles) and 'high normal' oestradiol levels (FSH cycles), while in three patients treated with FSH only, the LH surge was blocked, although the threshold level for the positive feedback effect had been exceeded by cycle day 9. We conclude that in women, supraphysiological concentrations of oestradiol exert a positive feedback effect on LH secretion. It is suggested that the occurrence of an LH surge in cycles superovulated with FSH is not dependent on serum oestradiol concentrations, but mainly on the strength of ovarian inhibitory substances.

Estradiol↗
PubMed1992

Gonadotrophin surge-attenuating factor attenuates in-vitro LH secretion induced by gonadotrophin-releasing hormone from cultured ovine pituitary cells only during the breeding season.

Primary cultures of ovine pituitaries from adult ewes were used to investigate aspects of gonadotrophin surge-attenuating factor (GnSAF) bioactivity in human follicular fluid (hFF) from superovulated women. During the autumn and first half of the winter, LH secretion induced by gonadotrophin-releasing hormone (GnRH) was markedly reduced (43.5 +/- 5.2% of control GnRH-induced LH secretion) by incubation for 48 h with steroid-free hFF. For the rest of the year, treatment with the same batch of steroid-free hFF resulted in non-significant reduction or stimulation of GnRH-induced LH secretion (71.3 +/- 13.2 to 117.8 +/- 11.2% of control GnRH-induced LH secretion). Incubation of pituitary cells for 48 h with oestradiol (1 pmol/l to 1 mumol/l), progesterone (1 pmol/l to 1 mumol/l) or oestradiol and progesterone combined (1 pmol/l to 1 mumol/l) in a two-way titration for 48 h had no significant effect on GnRH-induced LH secretion (83.4 +/- 7.6 to 110.6 +/- 5.0% of control secretion). Separating hFF into fractions of different molecular mass by ultrafiltration demonstrated that GnSAF bioactivity was present in a form 10-30 kDa in size. Incubation for 48 h with these fractions had no significant effect on basal FSH secretion but significantly attenuated GnRH-induced LH secretion during the autumn. The same fractions had little effect on GnRH-induced LH secretion from pituitary cells collected during the summer. We conclude that ovine pituitaries display at least partial reduction in sensitivity to GnSAF outside the breeding season.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Blunted prolactin response to exogenous luteinizing hormone releasing hormone in superovulated women.

To investigate the prolactin (PRL) response to luteinizing hormone releasing hormone (LHRH) in superovulated cycles, eight normally ovulating women were studied in two cycles, i.e. a spontaneous (control) and a cycle treated with 'pure' follicle stimulating hormone (FSH) (225 IU/day). LHRH was given to the women i.v. (a single injection of 100 micrograms) in the late follicular phase of both cycles. The oestradiol levels (mean +/- SEM) at the time of the LHRH challenge were 635 +/- 31 and 1707 +/- 225 pmol/l respectively (P less than 0.001). The size of the leading follicle was similar in both cycles. Basal PRL levels (mean +/- SEM) on the day of the LHRH experiment were significantly higher in the FSH (250 +/- 31 microIU/ml) than in the spontaneous cycles (133 +/- 15 microIU/ml. P less than 0.05). In the latter cycles, LHRH induced a significant increase in serum PRL and LH levels, while the FSH cycles, the prolactin (PRL) response to LHRH was blunted and LH response markedly attenuated. We conclude that superovulation induction stimulates basal but suppresses LHRH-induced PRL release. It is suggested that basal PRL secretion is LHRH-independent and the suppressing effect is mediated via previously described paracrine interactions between the gonadotrophs and lactotrophs and/or through ovarian inhibitory substances.

Adult↗
PubMed1991

Follicle stimulating hormone stimulates the production of gonadotrophin surge attenuating factor (GnSAF) in vivo.

OBJECTIVE: To study the time-course production of gonadotrophin surge attenuating factor (GnSAF) after the onset of FSH treatment in women. DESIGN: Normally cycling women were treated with FSH injections (225 IU per day) starting on cycle day 2 (0800 h). The response of LH to an i.v. injection of 10 micrograms GnRH (GnSAF bioactivity) was investigated 12, 24, 36 and 48 hours after the first FSH injection, as well as during the early follicular phase of an untreated spontaneous cycle. PATIENTS: Six normally ovulating women with long-standing unexplained infertility were studied. The women were used as their own controls during the spontaneous cycles. MEASUREMENTS: Pituitary response to GnRH was calculated as the net increase in LH at 30 min (delta LH30) above the basal value. RESULTS: delta LH30 was significantly attenuated 12, 24, 36 and 48 hours after the first FSH injection as compared to the spontaneous cycles. In the latter cycles, delta LH30 decreased significantly from day 2 (12 hours) to day 4 (48 hours). Serum oestradiol levels at 12 and 24 hours did not differ significantly between the FSH and the spontaneous cycles. CONCLUSIONS: These results demonstrate that in superovulated women, a marked attenuation in the pituitary response to GnRH occurs as early as 12 hours from a single injection of FSH before any significant increase in serum oestradiol levels. It is suggested that FSH is a potent stimulus of GnSAF production in women.

Biological Factors↗
PubMed1991

Attenuation of gonadotrophin release and reserve in superovulated women by gonadotrophin surge attenuating factor (GnSAF).

In-vivo and in-vitro studies have provided evidence that a non-steroidal ovarian factor, called gonadotrophin surge attenuating factor (GnSAF), attenuates the endogenous LH surge in superovulated women. To study the mechanism of action of GnSAF, the LH response to two i.v. pulses of GnRH (10 micrograms each, 2 h apart) was investigated in eight normally ovulating women during the late follicular phase of a spontaneous and an FSH superovulated cycle. The maximal LH increase in response to the first pulse (initial release) was considered as representing the acutely releasable pool and the delta LH area under the whole curve (integrated response) the reserve pool of LH. Both the initial release and the integrated response to GnRH were markedly attenuated in the FSH as compared to the spontaneous cycles. The response to the second pulse was significantly greater than the response to the first pulse (self-priming effect of GnRH) in both the spontaneous and the FSH cycles. However, in the FSH cycles the self-priming effect of GnRH was markedly reduced as compared to the spontaneous cycles. We conclude that during superovulation induction in women the two pools of pituitary LH are markedly attenuated. It is suggested that GnSAF attenuates both the GnRH-induced initial release of LH and the self-priming effect of GnRH on the pituitary.

Adult↗
PubMed1991

Follicular development in spontaneous and stimulated cycles in women with minimal-mild endometriosis.

OBJECTIVE: To study follicle development in women with minimal-mild endometriosis. DESIGN: In women with endometriosis a spontaneous ovulatory cycle was compared with two subsequent cycles in which either clomiphene or clomiphene and FSH were given to stimulate folliculogenesis. Spontaneous cycles in women with tubal infertility provided a comparison group. SETTING: Infertility clinic, Aberdeen Maternity Hospital. SUBJECTS: 17 women with minimal-mild endometriosis and 10 women with tubal infertility. INTERVENTIONS: The women with endometriosis were treated with 150 mg clomiphene citrate from days 2 to 6 in one cycle and in a subsequent cycle with 150 mg clomiphene citrate on days 2 to 6 plus 75 iu FSH daily thereafter. MAIN OUTCOME MEASURES: Follicular size measured daily using ultrasound. Serum FSH estimated on days 5 and 7 and then daily. RESULTS: Spontaneous follicular growth in the women with endometriosis was similar to that in the women with tubal infertility. Follicular development began earlier in cycles with clomiphene/FSH and the leading follicle reached 16 mm 2 days sooner but the rate of growth was similar whether or not either regimen of stimulation was used. CONCLUSION: Follicular growth is not impaired by minimal-mild endometriosis. Infertility with this condition cannot be explained by altered follicular growth or responsiveness.

Adult↗
PubMed1991

Evidence that gonadotrophin surge-attenuating factor exists in man.

This review article summarizes the evidence provided by in-vivo and in-vitro studies suggesting that the human ovary produces a nonsteroidal factor distinct from inhibin which participates in the control of gonadotrophin secretion from the pituitary. This factor has been called gonadotrophin surge-attenuating factor (GnSAF) and is defined as attenuating the endogenous surge in luteinizing hormone (LH) in superovulated women by reducing the pituitary response to LH-releasing hormone. In-vivo bioactivity of GnSAF has been detected during the follicular phase of superovulated cycles; in-vitro studies have shown activity of this factor in human follicular fluid. From a physiological point of view, a hypothesis is proposed that GnSAF attenuates the amplitude of the positive effect of oestradiol on gonadotrophin secretion during the follicular phase of the human menstrual cycle and therefore plays an important role in controlling ovulation. If GnSAF is isolated, it may have several clinical applications including contraception.

Animals↗
PubMed1990

Anti-oestrogenic effect of clomiphene citrate in oestrogen-treated, hypogonadal women.

The effect of clomiphene on the pituitary response to exogenous LHRH was investigated in five hypogonadal women during long-term treatment with varying doses of oestrogen. In three of them, basal LH levels were low (less than 10 mIU/ml) and increased significantly after 8 days of treatment with clomiphene (100 mg/day). Clomiphene augmented the LH and FSH response to LHRH (an acute i.v. injection of 100 micrograms) and changed the pattern of response into that seen in the absence of the influence of ovarian steroids. We conclude that clomiphene exerts anti-oestrogenic effects on basal and LHRH-stimulated release of gonadotrophins in hypogonadal women during long-term treatment with oestrogen.

Adult↗