Search Results

You are looking at 1 - 7 of 7 items for

  • Author: I. E. Messinis x
Clear All Modify Search
Free access

I. E. Messinis and A. A. Templeton

Summary. 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.

Keywords: LH surge; gonadotrophins; progesterone; oestradiol; man

Free access

I. E. Messinis and A. A. Templeton

Summary. Five normally ovulating women were induced to superovulate with pulsatile 'pure' FSH (28 i.u. every 3 h by a s.c. pump), and another 5 women were given an i.m. injection of 10 mg oestradiol benzoate in the late follicular phase. Serum oestradiol concentrations in the luteal phase were similar in both groups and significantly higher than in corresponding control cycles. The luteal phase was of shorter duration in the FSH (11·2 ± 0·7 days) than in the control (13·4 ± 0·2 days) and the oestrogen-treatment cycles (13·4 ± 0·7 days) (P < 0·05, mean ± s.e.m.). FSH cycles had significantly lower early luteal serum LH (Day 1:5·3 ± 1·5 mi.u./ml) and mid-luteal serum progesterone values (35·4 ± 3·5 nmol/l) compared with the control (27·8 ± 5·8 mi.u./ml and 65·4 ± 5·7 nmol/l, respectively) and oestrogen treatment cycles (25·3 ± 8·3mi.u./ml and 59·1 ± 8·4nmol/l, respectively) (P < 0·05, mean ± s.e.m.). These results suggest that, in hyperstimulated cycles, the luteal phase can be disrupted even without follicle aspiration, and that suppression of endogenous LH secretion may be responsible.

Free access

I. E. Messinis and A. A. Templeton

Summary. 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.

Keywords: LHRH; LH; FSH; pituitary; ovulation; man

Free access

I. E. Messinis and A. A. Templeton

Summary. 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 super-ovulated 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.

Keywords: LHRH; LH; FSH; pituitary; GnSAF; man

Free access

P. A. Fowler, I. E. Messinis and A. A. Templeton

Summary. 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.

Keywords: gonadotrophins; pituitary; follicular fluid; inhibin; gonadotrophin surge-attenuating factor; man

Free access

I. E. Messinis, A. MacTavish and A. A. Templeton

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 μg) 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.

Free access

I. E. Messinis, D. Lolis, K. Zikopoulos, E. Tsahalina, K. Seferiadis and A. A. Templeton

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 (ALH) to an injection of 10 μg 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, ALH 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 ALH lasted for the period when the FSH concentation was increased (3 days). A significant decrease in the basal concentration of LH was correlated with the increase in the oestradiol concentration. In group 2, ALH increased significantly between 4 and 8 h after treatment (LHRH self-priming effect) in both cycles. However, ALH was significantly attenuated in the FSH-treated cycles compared with the control cycles after 8, 12 and 24 h. At the same time, serum concentrations of oestradiol and immunoreactive inhibin did not change significantly. These results suggest that GnSAF is a nonsteroidal ovarian substance, different from inhibin, the production of which is dependent on FSH and which exerts potent antagonistic effects on the oestradiol-induced self-priming action of LHRH.