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Biomedical subjects

I E Messinis

Publications and source records attributed to I E Messinis.

At least 73 records · Page 4Linked to original sources
PubMed1990

The importance of follicle-stimulating hormone increase for folliculogenesis.

To study the role of the increase in follicle-stimulating hormone (FSH) during the early follicular phase of the menstrual cycle in folliculogenesis, eight normally cycling women were investigated in a spontaneous cycle (n = 8), a cycle treated with clomiphene citrate (n = 8), a cycle treated with FSH (n = 8) and a cycle treated with FSH plus pulsatile luteinizing-hormone-releasing hormone (LHRH) (n = 5). In the FSH and the FSH plus LHRH cycles, the leading follicle reached the size of 18 mm 2 days earlier on average than in the clomiphene-treated cycles. However, the rate of growth of the leading follicle was similar in the stimulated and the spontaneous cycles. At the same time, circulating levels of FSH differed greatly among the different groups of cycles. During the early follicular phase, serum FSH levels were significantly higher in the FSH plus LHRH and the FSH cycles than in the clomiphene and the spontaneous cycles. We conclude that the preovulatory stage of the dominant follicle is advanced by high FSH levels in the early follicular phase of the cycle. It is suggested that FSH controls follicle development in women at the recruitment--selection stage.

Clomiphene↗
PubMed1990

In-vivo bioactivity of gonadotrophin surge attenuating factor (GnSAF).

Gonadotrophin surge attenuating factor (GnSAF) is a nonsteroidal ovarian factor responsible for the attenuation of the endogenous LH surge in superovulated cycles. To study the bioactivity of GnSAF in vivo, the pituitary response to exogenous GnRH was investigated in 13 normally ovulating women during spontaneous and FSH-treated cycles. GnRH experiments were performed at three stages of both spontaneous and FSH cycles, i.e. early (n = 8), mid- (n = 8) and late follicular phase (n = 8). LH response to GnRH increased significantly from the early to late follicular phase in the spontaneous cycles, while in the FSH cycles it decreased significantly in mid- and increased in late follicular phase. A marked attenuation of the LH response to GnRH during both the mid- and late follicular phase was seen in the FSH as compared to the corresponding spontaneous cycles. We conclude that in superovulated cycles small, growing follicles produce GnSAF.

Biological Factors↗
PubMed1990

Prolactin secretion in women during the oestradiol-induced luteinizing hormone surge with or without progesterone.

To study the role of progesterone (P4) in the control of PRL increase during the midcycle LH surge, eight normally ovulating women were treated with i.m. injections of oestradiol benzoate (E2B) every 12 h during the early follicular phase of two different cycles (from cycle days 2 to 4). In the second cycle P4 injections were also given to the women every 12 h starting at the end of the E2B treatment (from cycle days 4 to 6). Circadian periodicity of serum PRL levels during the E2-induced LH surge did not differ significantly between the E2B and the E2B + P4 experiments. Evening PRL levels increased significantly in both experiments with a peak during the LH surge and no significant difference between them. We conclude that administration of P4 to normal women does not alter the increase in PRL secretion during the LH surge induced by exogenous oestrogen. It is suggested that P4 is not involved in the mechanism controlling midcycle PRL secretion.

Circadian Rhythm↗
PubMed1990

Superovulation induction in women suppresses luteinizing hormone secretion at the pituitary level.

In superovulated women the pituitary response to GnRH is markedly attenuated by an unspecified ovarian factor(s). To examine the site of attenuation, the response of the pituitary to GnRH was investigated in five normally ovulating women during the late follicular phase of 3 cycles, i.e. a spontaneous (control) cycle, a cycle treated with 'pure' FSH, and a cycle treated with a combination of 'pure' FSH and pulsatile GnRH, via a pump (15 micrograms/pulse). The oestradiol levels (mean +/- SEM) at the time of the GnRH challenge were respectively 646 +/- 35, 1692 +/- 282 and 5976 +/- 1129 pmol/l. The size of the leading follicle was similar in all groups. Serum LH levels during treatment with FSH decreased significantly, while during treatment with FSH plus GnRH they increased initially and then decreased progressively. The response of pituitary LH to GnRH was significantly attenuated during treatment with FSH and FSH plus GnRH, as compared to the spontaneous cycles, but was not abolished. The attenuation was significantly greater in the FSH plus GnRH cycles (94%) than in the FSH cycles (59%). We conclude that in superovulated cycles, the attenuation of the pituitary response to GnRH increases with the degree of ovarian hyperstimulation. It is suggested that the responsible unspecified ovarian factor(s) exerts its effects at least at the pituitary level.

Female↗
PubMed1990

Effects of supraphysiological concentrations of progesterone on the characteristics of the oestradiol-induced gonadotrophin surge in women.

Intramuscular injections of oestradiol benzoate were given to 8 normally cyclic women in the early follicular phase of 3 different cycles. Progesterone was also injected in the second (low dose) and the third cycle (high dose). Oestradiol induced simultaneous surges of LH and FSH in all women and the onset of these surges was advanced by progesterone. Low-dose progesterone induced a significant increase in the amplitude and the duration of the LH and FSH surges, while high-dose progesterone decreased the duration significantly. In contrast to the oestrogen-only treatment cycles, when the women were treated with progesterone, basal LH and FSH concentrations were suppressed significantly not only before the onset but also after the end of the surge. The results suggest that progesterone affects the dimension of the oestradiol-induced gonadotrophin surge by exerting both a stimulatory and an inhibitory effect on pituitary gonadotrophin secretion. Supraphysiological concentrations of progesterone decreased the duration of the oestradiol-induced gonadotrophin surge significantly and this is possibly part of the mechanism which attenuates the endogenous LH surge in women superovulated for in-vitro fertilization.

Depression, Chemical↗
PubMed1990

Inhibition of LHRH-induced LH and FSH release by gonadotrophin surge-attenuating factor (GnSAF) from human follicular fluid.

It has been suggested that in superovulated women the endogenous LH surge is attenuated by a non-steroidal factor, called gonadotrophin surge-attenuating factor (GnSAF), which reduces gonadotrophin secretion in response to LHRH. To determine whether human follicular fluid (hFF) from superovulated women contains GnSAF activity, the secretion of LH and FSH by cultured sheep pituitaries was studied. After charcoal extraction of steroids, hFF was treated by heparin/Sepharose chromatography, which reversibly binds inhibin. The effects of whole hFF and the bound and unbound fractions on basal and LHRH-induced gonadotrophin secretion were then assessed. Steroid-free hFF significantly reduced basal FSH, but not basal LH, secretion, and significantly attenuated the LH and FSH responses to LHRH. The bound (inhibin) fraction significantly decreased both basal and LHRH-induced FSH secretion but did not affect LH release. The unbound fraction had no effect on basal LH or FSH secretion, but significantly attenuated LHRH-induced secretion of both LH and FSH. We conclude that the unbound fraction of hFF from superovulated women contains GnSAF. It has been demonstrated that GnSAF is a non-steroidal factor and its activity is distinct from that of inhibin.

Animals↗
PubMed1989

Pituitary response to exogenous LHRH in superovulated women.

The response of the pituitary to exogenous LHRH was investigated in 9 normally ovulating women during the late follicular phase of a spontaneous (control) cycle, a cycle during treatment with clomiphene and a cycle during treatment with 'pure' FSH. During clomiphene treatment, basal FSH concentrations increased significantly up to Day 6 of the cycle and then decreased progressively while basal LH values showed a continuous rise. During treatment with FSH, basal LH concentrations decreased significantly. The response of both FSH and LH to LHRH showed a significant and quantitatively similar decrease during clomiphene or FSH administration as compared to the spontaneous cycles. It is suggested that basal secretion of FSH and LH is regulated by two separate mechanisms, and that an ovarian inhibitory factor(s) attenuates the response of both FSH and LH to exogenous LHRH and possibly the endogenous LH surge in superovulated cycles.

Clomiphene↗
PubMed1989

Drugs used in in vitro fertilisation procedures.

The drugs used in in vitro fertilisation (IVF) procedures have the ability to stimulate the ovaries either directly or indirectly to cause multiple follicular development. In most centres today combinations of drugs in various regimens are used and a large number of oocytes are obtained for in vitro fertilisation. Despite that, the overall pregnancy rate is still low, and has improved little during the last 5 years. Possible effects of the drugs on the oocyte maturation process and the endocrinology of the menstrual cycle may contribute to the low success rate. The recent use of gonadotrophin releasing hormone (GnRH) analogues which block endogenous gonadotrophin secretion, in combination with controlled stimulation of the ovaries with exogenous gonadotrophins, tends to be more successful. However, more suitable protocols for better synchronisation of follicle development and a reduction in the cost of the drugs are required to make in vitro fertilisation a more readily available method for the treatment of infertility.

Clomiphene↗
PubMed1988

Effect of cimetidine on maternal and fetal prolactin secretion during labor.

Cimetidine, an H2 receptor antagonist, is a potent stimulant of PRL secretion in normal women. In the present study, the PRL response to cimetidine was studied in 34 normal pregnant women and their fetuses during labor. Serum maternal PRL levels increased significantly after the acute iv injection of 400 mg cimetidine 30-45 min before delivery (10 women) as compared to 7 control women given saline. However, PRL levels in serum of umbilical vein and artery did not increase. Similar results concerning PRL levels in umbilical vein and artery serum were obtained when cimetidine was injected 10-20 min (8 women), 60-75 min (8 women) and 90-120 min (8 women) before delivery. It is suggested that fetal pituitary lactotrops are not responsive to cimetidine stimulation.

Cimetidine↗
PubMed1988

The importance of human chorionic gonadotropin support of the corpus luteum during human gonadotropin therapy in women with anovulatory infertility.

One hundred ten women with anovulatory infertility (World Health Organization [WHO] group I n = 50, WHO group II n = 60) were given 341 treatment courses with human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG). Additional hCG was given as single or repeated injections during the luteal phase in 205 ovulatory cycles. In WHO group I, the incidence of luteal phase defects was lower and the pregnancy rate higher in cycles with extra hCG administration during the luteal phase than in cycles with no extra hCG. In WHO group II, there was no such difference after supplemental hCG. The abortion rate was the same after cycles with or without extra hCG administration. It is suggested that during ovulation induction with hMG/hCG in anovulatory women with no evidence of endogenous estrogen activity, the luteal phase should be supplemented with additional hCG.

Adult↗
PubMed1988

Changes in serum prolactin levels during the follicular phase and the endogenous luteinizing hormone surge of cycles hyperstimulated with follicle stimulating hormone.

The pattern of serum PRL levels during superovulation induction with pulsatile 'pure' FSH was investigated in 10 normally ovulating women. They were studied in two consecutive cycles, i.e. an untreated spontaneous and an FSH stimulated cycle. An endogenous LH surge occurred in all 10 spontaneous cycles and in five of the FSH cycles. Midcycle PRL levels were significantly higher in the FSH stimulated than in the spontaneous cycles (P less than 0.01). In both groups of cycles, circadian periodicity of serum PRL levels during the LH surge was different from that during the late follicular phase with higher levels at midnight, although in the FSH cycles PRL secretion showed a sustained increase over 24 h. A nadir of PRL levels was found between 0900 h and 1200 h. In contrast, progesterone secretion during the LH surge showed a nocturnal increase with the highest value between 0600 h and 1200 h and the lowest at midnight. In the FSH cycles without an LH surge, PRL levels increased as long as FSH administration was continued and showed a significant positive correlation with the increasing serum oestradiol levels (r = 0.77). We conclude that ovarian hyperstimulation is a potent stimulus of PRL secretion in women. It is suggested that the midcycle endogenous LH surge facilitates the evening PRL secretion, while induction of multiple folliculogenesis amplifies the 24 h pattern of PRL secretion.

Circadian Rhythm↗
PubMed1988

Blockage of the positive feedback effect of oestradiol during prolonged administration of clomiphene citrate to normal women.

The effect of clomiphene citrate on the occurrence and timing of the endogenous LH surge in superovulated cycles is unclear. To study further this event, five normally ovulating women were treated with clomiphene citrate 100 mg per day in two different cycles, that is, for 5 days in one cycle (days 2 to 6, CC-5) and for 15 days in another cycle (days 2 to 16, CC-15). During the CC-5 cycle, the normal pattern of LH levels seen in spontaneous cycles was observed with an endogenous LH surge in all women followed by ovulation and normal luteal function. In contrast, during the CC-15 cycle, a continuous and progressive increase of basal LH levels was seen with no surge, resulting in follicular luteinization but no ovulation. The results suggest that in normal women treated with clomiphene the occurrence of an endogenous LH surge is dependent on a significant decrease in the circulatory concentration of clomiphene at mid-cycle.

Clomiphene↗
PubMed1988

The effect of the antiprogestin mifepristone (RU 486) on maturation and in-vitro fertilization of human oocytes.

The effect of RU 486 (mifepristone), a potent antiprogestin, on the in-vitro fertilization of human oocytes was investigated. In 40 normal volunteer women requesting laparoscopic sterilization, follicle aspiration for oocyte recovery was attempted 34 h after the injection of 5000 i.u. human chorionic gonadotrophin (hCG). Twenty women were allocated to receive 100 mg RU 486 orally 1 h before the hCG injection, the remaining 20 women acted as controls. There was no significant difference in the cleavage rate of the oocytes after fertilization in vitro between the two groups (56% and 66% respectively). Also, the morphological characteristics of the cleaving oocytes and the concentrations of oestradiol, progesterone and androstenedione in the follicular fluid of the leading follicle did not differ significantly between the two groups. Since RU 486 was detected in substantial amounts in the follicular fluid specimens, these results suggest that progesterone is not critical for the final stages of human oocyte maturation.

Estrenes↗
PubMed1988

Gonadotropic stimulation of inhibin secretion by the human ovary during the follicular and early luteal phase of the cycle.

We studied the pattern of secretion of inhibin bioactivity from the ovary into peripheral blood during the follicular and early luteal phase of the menstrual cycle in women receiving gonadotropin therapy. Multiple follicular development was stimulated in 5 women undergoing in vitro fertilization and embryo transfer for tubal infertility using three different treatments designed to vary the concentration of FSH and LH (14 cycles). The women received clomiphene citrate (150 mg/day) from days 2-6 alone or supplemented with either exogenous human menopausal gonadotropin (28 IU/3 h) or pure FSH (28 IU/3 h) from day 6 until the day of follicle aspiration. Inhibin concentrations increased 10-fold in parallel with those of estradiol, from 0.2-0.3 U/mL on day 2 (before the onset of treatment) to 4-5 U/mL on day 14 of the cycle (time of the peak LH level). Coincidental to the LH surge, the inhibin concentration declined 2- to 3-fold before increasing again early in the luteal phase. The concentration of inhibin was higher in the gonadotropin-treated group (clomiphene plus human menopausal gonadotropin/FSH) than in the group treated with only clomiphene during the follicular phase. The number of follicles stimulated was significantly higher (P less than 0.001) in the group given exogenous gonadotropins [4.8 +/- 0.4 (SE)] than in the clomiphene alone group (2.2 +/- 0.4). These data strongly suggest that both the Graafian follicles and the corpus luteum secrete inhibin, which together with estradiol and progesterone may play a role in the regulation of FSH secretion during the luteal phase.

Adult↗
PubMed1988

Treatment of premenstrual mastalgia with tamoxifen.

Thirty-four women with normal menstrual cycles but suffering from severe premenstrual mastalgia were randomly treated with either tamoxifen (10 mg daily) (18 women) or placebo (16 women) from cycle day 5 to 24 for six consecutive cycles. At the end of the treatment, 89% of the tamoxifen-treated patients were free from the symptoms and the remainder experienced partial alleviation. In contrast, six patients treated with placebo showed only partial alleviation (38%) (p less than 0.001). Twelve months after the end of tamoxifen treatment, 53% of the medicated women were still free of symptoms as compared with none of the placebo-treated patients. These results suggest that tamoxifen is highly effective for the management of severe premenstrual mastalgia and should be useful for the treatment of this disorder.

Adult↗
PubMed1987

Endocrine and follicle characteristics of cycles with and without endogenous luteinizing hormone surges during superovulation induction with pulsatile follicle-stimulating hormone.

The induction of superovulation in women with human gonadotrophins may result in blockage of the endogenous luteinizing hormone (LH) surge, but the reasons for this are not known. Ten normally ovulating women with longstanding infertility volunteered for this study. They were treated with 225 IU follicle-stimulating hormone (FSH) daily s.c. in a pulsatile manner (28 IU every 3 h) starting on cycle day 2. Serum FSH and oestradiol levels increased and serum LH levels decreased significantly during the FSH treatment, as compared to their spontaneous cycles. Only five women displayed an LH surge during the FSH treatment. Serum FSH and LH levels during treatment were significantly lower and the number of follicles 12-15 mm in diameter and their total fluid volume was significantly greater in the cycles without an endogenous LH surge. Basal LH levels in the cycles without an LH surge increased soon after the end of the FSH treatment (cycle day 18), while FSH levels were still very low without any incremental tendency. These results suggest that a high number of small follicles may have a suppressive effect on both tonic and mid-cycle gonadotrophin secretion. Furthermore, the LH suppressive mechanism seems to be different from that of the FSH.

Female↗