Effect of epidermal growth factor on reproductive function of ewes

1985 ◽  
Vol 107 (3) ◽  
pp. 429-436 ◽  
Author(s):  
G. Shaw ◽  
G. I. Jorgensen ◽  
R. Tweedale ◽  
M. Tennison ◽  
M. J. Waters
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Luteal Phase ◽  
Reproductive Function ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Follicular Phase ◽  
Plasma Progesterone ◽  
Lh Surge ◽  
Epidermal Growth

ABSTRACT Adult Merino ewes were infused via the jugular vein with either saline (n = 5) or epidermal growth factor (EGF) (4·2 μg/kg per h, n = 6) for 24 h in either the luteal phase or the follicular phase of the oestrous cycle and reproductive function was examined. Infusion of EGF during the luteal phase caused no detectable change in plasma progesterone or prolactin concentrations over a 7-day period compared with the controls. Infusion of EGF during the follicular phase suppressed the oestrous rise in plasma oestradiol. Luteinizing hormone pulse amplitude was increased and pulse frequency was decreased by the end of the infusion. All control ewes had a pro-oestrous LH surge and mated, but the LH surge and oestrus were prevented by EGF infusion. Nevertheless, plasma progesterone levels rose subsequently in the EGF-infused ewes in parallel with the control ewes, suggesting that the preovulatory follicle had luteinized. Both LH and FSH rose over the 7 days after EGF infusion to levels similar to those in ovariectomized ewes. Thus EGF appears to inhibit follicular oestradiol production, although it does not affect luteal progesterone production or follicular luteinization. We suggest that the alteration in gonadotrophin secretion patterns results from a disturbance of feedback mechanisms between the ovary and the hypothalamopituitary axis, although a direct effect in the brain or the pituitary gland cannot yet be excluded. J. Endocr. (1985) 107, 429–436

Effect of the body condition of ewes on the secretion of LH and FSH and the pituitary response to gonadotrophin-releasing hormone

1989 ◽  
Vol 120 (3) ◽  
pp. 497-502 ◽  
Author(s):  
S. M. Rhind ◽  
S. McMillen ◽  
W. A. C. McKelvey ◽  
F. F. Rodriguez-Herrejon ◽  
A. S. McNeilly
Keyword(s):  
Body Condition ◽  
Luteal Phase ◽  
Body Condition Score ◽  
Pulse Amplitude ◽  
Ovarian Hormones ◽  
Pulse Frequency ◽  
Follicular Phase ◽  
High Body ◽  
Condition Score ◽  
Gonadotrophin Releasing Hormone

ABSTRACT The effects of body fat content (body condition) of ewes on hypothalamic activity and gonadotrophin-releasing hormone (GnRH) secretion and on pituitary sensitivity to GnRH were investigated using Scottish Blackface ewes. Two groups of 12 ewes were fed so that they achieved either a high body condition score (2·98, s.e.m. = 0·046; approximately 27% of empty body weight as fat) or a low body condition score (1·94, s.e.m. = 0·031; approximately 19% of empty body weight as fat) by 4 weeks before the period of study. Thereafter, they were differentially fed so that the difference in mean condition score was maintained. Oestrus was synchronized, and on day 11 of the subsequent cycle half of the ewes of each group were ovariectomized. On day 12, the remaining ewes were injected (i.m.) with 100 μg prostaglandin F2α analogue and ovariectomized 30 h later. Numbers of large ovarian follicles and corpora lutea present at ovariectomy were recorded. Blood samples were collected at 15-min intervals for 12 h on day 10 of the cycle (luteal phase) and at 10-min intervals from 24 to 30 h after prostaglandin injection (follicular phase). At days 2 and 7 after ovariectomy, samples were collected at 15-min intervals for 8 h and ewes were then injected with 10 μg GnRH and samples were collected for a further 3 h. Samples were assayed for LH and FSH. Ewes in high body condition had more more large follicles than ewes in low body condition during the luteal phase (15·3 vs 6·5; P < 0·05) and follicular phase (11·5 vs 7·0; NS) and a slightly higher mean ovulation rate (1·50 vs 1·20; NS). However, during the luteal and follicular phases of the cycle before ovariectomy there was no effect of condition score on mean LH or FSH concentrations or mean LH pulse frequency or pulse amplitude. Two days after ovariectomy, ewes of high body condition had a higher mean LH pulse frequency than ewes of low body condition (P < 0·05) and higher mean FSH concentrations (P < 0·05). Mean LH concentration and pulse amplitude were not affected. LH and FSH profiles were not affected by body condition on day 7. GnRH-induced increases in LH and FSH concentrations on days 2 and 7 were not affected by body condition. At day 7, but not day 2, ewes ovariectomized during the luteal phase of the cycle had a significantly (P < 0·05) greater GnRH-induced LH release compared with ewes ovariectomized during the follicular phase. It is concluded that body condition directly affects hypothalamic activity and GnRH secretion, but not pituitary sensitivity to GnRH, and that effects on reproductive performance are also mediated through changes in ovarian hormones or in hypothalamo-pituitary sensitivity to ovarian hormones. Journal of Endocrinology (1989) 120, 497–502

Evidence that the switch from negative to positive feedback at the level of the pituitary gland is an important timing event for the onset of the preovulatory surge in LH in the ewe

1995 ◽  
Vol 145 (2) ◽  
pp. 271-282 ◽  
Author(s):  
I J Clarke
Keyword(s):  
Pituitary Gland ◽  
Negative Feedback ◽  
Luteal Phase ◽  
Bolus Injection ◽  
Pulse Frequency ◽  
Follicular Phase ◽  
Oestrous Cycle ◽  
Lh Surge ◽  
Small Rise ◽  
Lh Secretion

Abstract Experiments were performed to test the hypothesis that there is a negative feedback 'clamp' of ovarian hormones on the hypothalamus and pituitary gland during the follicular phase of the oestrous cycle that limits the secretion of GnRH and LH. GnRH secretion was monitored by sampling the hypophysial portal blood of ewes during the luteal phase of the oestrous cycle and either 24 h or 48 h after the induction of luteolysis by the injection of cloprostenol, a prostaglandin analogue. There was an increase in GnRH pulse frequency in the transition from the luteal to the follicular phase of the cycle. A reduction in the amplitude of GnRH pulses did not occur until 48 h after cloprostenol, suggestive of negative feedback at the level of the hypothalamus that is more profound in the latter part of the follicular phase. The responsivity of the pituitary gland to GnRH was monitored in ewes during the luteal phase of the oestrous cycle and 24 h or 48 h after cloprostenol. Injections of 250 ng or 1000 ng GnRH were given (i.v.) to ewes that had been anaesthetised to suppress endogenous secretion of GnRH and LH. Using the lower dose, the responses 48 h after cloprostenol were not significantly different from those in the luteal phase. With the higher dose of GnRH, a significant (P<0·05) increase in mean responsivity was seen 48 h after cloprostenol. There was, however, a marked variation in response, with some ewes showing profound increases in LH secretion in response to GnRH and others showing responses that were similar to those obtained during the luteal phase of the cycle. These data are interpreted to mean that the secretion of LH is 'clamped' during the follicular phase of the oestrous cycle and the 'clamp' is only released near the time of the preovulatory LH surge. To test whether or not a rise in GnRH input to the pituitary gland could over-ride the 'clamp' on the pituitary secretion of LH in the late follicular phase of the cycle, sheep were treated 40 h after cloprostenol with either a bolus injection of 500 ng GnRH or four pulses of 125 ng GnRH given at 10-min intervals. These treatments caused small elevations in LH secretion but did not always cause preovulatory LH surges. In some cases, a small rise in LH secretion was induced by GnRH treatments and levels of LH in plasma returned to baseline with the preovulatory LH surge occurring a few hours later. In one clear case, a bolus injection of GnRH induced an LH surge. The overall data from the GnRH-treated groups, however, indicated a significant delay in the onset of the LH surge which may have been due to perturbation of the subcellular mechanisms in the gonadotrophs. These data were interpreted to mean that the secretion of LH from the pituitary gland is inhibited up to very soon before the onset of the LH surge. The inhibitory factor could be oestrogen but could also be some other pituitary feedback hormone such as gonadotrophin surge-attenuating factor. It is concluded that the increase in the secretion of GnRH at the time of the onset of the LH surge is closely linked to an increase in the responsivity of the gonadotrophs to GnRH. The latter is not caused by the increase in the secretion of GnRH. Journal of Endocrinology (1995) 145, 271–282

Some effects of epidermal growth factor at three stages of pregnancy in Merino ewes

1991 ◽  
Vol 42 (8) ◽  
pp. 1301
Author(s):  
IG Hazelton ◽  
BA Panaretto ◽  
PR Stockwell ◽  
JT Marshall ◽  
CD Nancarrow
Keyword(s):  
Body Weight ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Gestational Age ◽  
Untreated Control ◽  
Induced Abortion ◽  
Mechanisms Of Action ◽  
Plasma Progesterone ◽  
Epidermal Growth ◽  
Three Stages

Pregnant Merino ewes were treated with 90 8g murine epidermal growth factor (EGF) per kg body weight at either 25 (n = 80), 50 (n= 40) or 75 (n =40) days of gestation. Untreated control ewes were included at each gestational age (n=20, 12 and 12 respectively). Fifteen and twenty per cent of the ewes treated with EGF at days 25 and 50 respectively failed to lamb, significantly more (P < 0.01 ) than in ewes treated at day 75, where only one ewe failed to lamb, and in control ewes which all lambed. These differences were not reflected in significant differences between the overall percentage of lambs born in each group, as the incidence of abortion in single-bearing ewes was higher than in ewes carrying multiple fetuses. All lambs born alive to EGF-treated ewes appeared normal. Plasma progesterone concentrations measured before treatment and at 8, 24 and 48 h after EGF injection fell significantly in treated ewes relative to controls (P<0.01 at day 25; P<0.05 at days 50 and 75) and concentrations were lowest at 8 and 24 h after injection in those ewes which aborted. Following EGF treatment at days 25 and 50 of gestation, abortion occurred in all ewes with very low plasma progesterone concentrations 8 to 48 h after EGF injection, probably as a result of EGF-induced luteolysis. In other ewes plasma progesterone concentrations returned to pretreatment values by 48 h, indicating incomplete luteolysis. The delayed abortion observed in some of these ewes further suggests that other mechanisms of action are involved in EGF-induced abortion.

LUTEINIZING HORMONE LEVELS DURING THE MENSTRUAL CYCLE OF THE BABOON (PAPIO HAMADRYAS)

1979 ◽  
Vol 91 (1) ◽  
pp. 49-58 ◽  
Author(s):  
N. Goncharov ◽  
A. V. Antonichev ◽  
V. M. Gorluschkin ◽  
L. Chachundocova ◽  
D. M. Robertson ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Luteinizing Hormone ◽  
Plasma Levels ◽  
Luteal Phase ◽  
Follicular Phase ◽  
Papio Hamadryas ◽  
Biologically Active ◽  
Plasma Progesterone ◽  
Lh Surge

ABSTRACT The peripheral plasma levels of luteinizing hormone (LH) as measured by an in vitro bioassay method were determined in daily plasma samples collected throughout one menstrual cycle in 8 normally menstruating baboons (Papio hamadryas). In addition LH was measured in plasma at three hourly intervals throughout the day in the follicular, peri-ovulatory and luteal phases of the cycle in 7, 3 and 6 animals respectively. The plasma levels of progesterone and oestradiol were also determined in the same samples throughout the menstrual cycle and during the period of the midcycle LH surge. The circulating LH profile measured throughout the cycle was characterized by a sharp mid-cycle surge (completed within one day) which was followed by a series of LH surges of varying intensity during the luteal phase of the cycle. The initial surge was considered to be pre-ovulatory as indicated by its relationship to the peak of plasma oestradiol and to the first significant increase in the levels of plasma progesterone above values found earlier in the follicular phase. A circadian rhythm of LH was observed during the luteal phase of the cycle; a 3 fold rise in LH was noted during the hours 15.00 to 24.00. No differences were observed throughout the day in the follicular phase of the cycle. The LH profile in three animals studied during the mid-cycle LH surge showed pronounced circadian changes with a major peak at 24.00 h. Plasma progesterone levels during this period rose sharply to values normally found in the mid-luteal phase of the cycle. A comparison of plasma levels of biologically active LH during the menstrual cycle of the baboon with those found in normally menstruating women reveals that in the baboon the LH peak is of much shorter duration and the levels in the follicular and peri-menstrual phases are significantly lower than in the human.

scholarly journals Effects of hyperandrogenemia and increased adiposity on reproductive and metabolic parameters in young adult female monkeys

2014 ◽  
Vol 306 (11) ◽  
pp. E1292-E1304 ◽  
Author(s):  
W. K. McGee ◽  
C. V. Bishop ◽  
C. R. Pohl ◽  
R. J. Chang ◽  
J. C. Marshall ◽  
...  
Keyword(s):  
Luteal Phase ◽  
Polycystic Ovary ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Follicular Phase ◽  
Antral Follicles ◽  
Reproductive Axis ◽  
Early Follicular Phase ◽  
Follicular Size ◽  
Cholesterol Control

Many patients with hyperandrogenemia are overweight or obese, which exacerbates morbidities associated with polycystic ovary syndrome (PCOS). To examine the ability of testosterone (T) to generate PCOS-like symptoms, monkeys received T or cholesterol (control) implants ( n = 6/group) beginning prepubertally. As previously reported, T-treated animals had increased neuroendocrine drive to the reproductive axis [increased luteinizing hormone (LH) pulse frequency] at 5 yr, without remarkable changes in ovarian or metabolic features. To examine the combined effects of T and obesity, at 5.5 yr (human equivalent age: 17 yr), monkeys were placed on a high-calorie, high-fat diet typical of Western cultures [Western style diet (WSD)], which increased body fat from <2% (pre-WSD) to 15–19% (14 mo WSD). By 6 mo on WSD, LH pulse frequency in the controls increased to that of T-treated animals, whereas LH pulse amplitude decreased in both groups and remained low. The numbers of antral follicles present during the early follicular phase increased in both groups on the WSD, but maximal follicular size decreased by 50%. During the late follicular phase, T-treated females had greater numbers of small antral follicles than controls. T-treated monkeys also had lower progesterone during the luteal phase of the menstrual cycle. Although fasting insulin did not vary between groups, T-treated animals had decreased insulin sensitivity after 1 yr on WSD. Thus, while WSD consumption alone led to some features characteristic of PCOS, T + WSD caused a more severe phenotype with regard to insulin insensitivity, increased numbers of antral follicles at midcycle, and decreased circulating luteal phase progesterone levels.

scholarly journals Some effects of epidermal growth factor on reproductive function in Merino sheep

Reproduction ◽  
1987 ◽  
Vol 80 (1) ◽  
pp. 113-118 ◽  
Author(s):  
H. M. Radford ◽  
J. A. Avenell ◽  
B. A. Panaretto
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Reproductive Function ◽  
Merino Sheep ◽  
Epidermal Growth

scholarly journals Effect of Sialoadenectomy on the Level of Circulating Mouse Epidermal Growth Factor (mEGF) and on the Reproductive Function in Male Mice

1988 ◽  
Vol 5 (3) ◽  
pp. 221-229 ◽  
Author(s):  
Noriaki TOKIDA ◽  
Ichizo SHINODA ◽  
Masayuki KUROBE ◽  
Yukihiro TATEMOTO ◽  
Masahiko MORI ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Reproductive Function ◽  
Male Mice ◽  
Epidermal Growth

Pulsatile secretion of inhibin, oestradiol and androstenedione by the ovary of the sheep during the oestrous cycle

1990 ◽  
Vol 126 (3) ◽  
pp. 385-393 ◽  
Author(s):  
B. K. Campbell ◽  
G. E. Mann ◽  
A. S. McNeilly ◽  
D. T. Baird
Keyword(s):  
Luteal Phase ◽  
Venous Blood ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Follicular Phase ◽  
Oestrous Cycle ◽  
Blood Samples ◽  
Early Follicular Phase ◽  
Lh Secretion ◽  
Late Follicular Phase

ABSTRACT The pattern of pulsatile secretion of inhibin, oestradiol and androstenedione by the ovary at different stages of the oestrous cycle in sheep was studied in five Finn–Merino ewes in which the left ovary had been autotransplanted to the neck. The ewes had jugular venous blood samples collected at 4-hourly intervals from 42 h before the induction of luteolysis by i.m. injection of cloprostenol (100 μg) on day 10 of the oestrous cycle, until day 3 of the following cycle. There were five periods of intensive blood sampling, when both ovarian and jugular venous blood samples were collected, as follows: (a) mid-luteal phase, before the second injection of cloprostenol on day 10 (15-min intervals for 6 h); (b) early follicular phase, 24 h after the second injection of cloprostenol (10-min intervals for 4 h); (c) late follicular phase, 48 h after the second injection of cloprostenol (10-min intervals for 4 h); (d) after the LH surge on day 1 of the cycle, 76 h after the second injection of cloprostenol (10-min intervals for 4 h); (e) early luteal phase on day 3 of the cycle, 120 h after the second injection of cloprostenol (10-min intervals for 3 h). Plasma was collected and the samples assayed for LH, FSH, progesterone, oestradiol, androstenedione and inhibin. The ovarian secretion rates for oestradiol, androstenedione and inhibin were calculated. All ewes responded normally to the luteolytic dose of cloprostenol with the preovulatory surge of LH occurring within 56·4±1·6 h (mean ± s.e.m.) followed by the establishment of a normal luteal phase. The pulse frequency of LH, oestradiol and androstenedione increased in the transition from the luteal to the follicular phase (P<0·01). On day 1 of the cycle LH secretion consisted of low-amplitude high-frequency pulses (1·0±0·1 pulse/h) to which androstenedione, but not oestradiol, responded. On day 3 of the cycle LH secretion was similar to that on day 1 but both androstenedione and oestradiol secretion were pulsatile in response to LH, indicating the presence of oestrogenic follicles. The stage of the cycle had no significant effects on LH pulse amplitude and nadir but the ovarian secretory response to LH stimulation did vary with the stage of the cycle. Prolactin pulse frequency, amplitude and nadir were higher (P<0·05) during the follicular phase than the luteal phase. Prolactin pulse frequency was depressed (P<0·05) on day 1 of the cycle but increased to follicular phase levels on day 3. Prolactin pulse frequency was significantly correlated to oestradiol pulse frequency (r = 0·54; P<0·01). During the luteal phase there were insufficient oestradiol pulses to obtain an estimate of pulse amplitude and nadir but both these parameters reached their highest level during the late follicular phase, fell to negligible levels on day 1 and increased to early follicular phase levels on day 3. Androstenedione pulse amplitude and nadir exhibited similar but less marked variation. Inhibin secretion was episodic at all stages of the cycle examined but did not exhibit significant variation with stage of cycle in any of the parameters of episodic secretion measured. Inhibin pulses were not related to either LH or prolactin at any stage of the cycle. FSH secretion was not detectably pulsatile but jugular venous concentrations of FSH at each stage of the oestrous cycle were negatively correlated with mean oestradiol (r= −0·52; P<0·01 but not inhibin secretion (r = 0·19). We conclude that (i) LH secretion is pulsatile at all stages of the oestrous cycle but the steroidogenic responses of the ovary varies with the stage of the cycle, reflecting changes in characteristics of the follicle population, (ii) ovarian inhibin secretion is episodic and displays little change with the stage of the oestrous cycle and (iii) episodic inhibin secretion is not related to either pulses of LH or prolactin. The aetiology of these inhibin pulses therefore remains unknown. Journal of Endocrinology (1990) 126, 385–393

Changes in the secretion of LH pulses, FSH and prolactin during the preovulatory phase of the oestrous cycle of the ewe and the influence of treatment with bovine follicular fluid during the luteal phase

1988 ◽  
Vol 116 (1) ◽  
pp. 123-135 ◽  
Author(s):  
J. M. Wallace ◽  
G. B. Martin ◽  
A. S. McNeilly
Keyword(s):  
Follicular Fluid ◽  
Luteal Phase ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Ovarian Follicles ◽  
Follicular Phase ◽  
Oestrous Cycle ◽  
Ovulation Rate ◽  
The Other ◽  
Lh Secretion

ABSTRACT It has previously been shown that treatment of ewes with bovine follicular fluid (bFF) throughout the luteal phase of the oestrous cycle lowers plasma levels of FSH but increases the frequency and amplitude of the pulses of LH. Under these conditions, ovarian follicles grow to a maximum diameter of 2·7 mm and have a reduced capacity to release oestradiol. We have examined the nature of the gonadotrophin signals controlling follicular development in the normally cycling ewe and have investigated the effects of previous exposure to bFF on these signals and the follicular responses to them. Control ewes (n = l) were injected i.v. with 9 ml bovine serum and treated ewes were injected with 9 ml bFF, twice daily from days 1 to 10 of the luteal phase (day 0 = oestrus). The ewes were injected with prostaglandin analogue on day 11 of the cycle to induce luteolysis and the gonadotrophin patterns were studied in blood sampled from these animals every 10 min for up to 72 h during the subsequent follicular phase. Following luteolysis (and the end of bFF treatment), LH pulse frequency increased rapidly in both groups and reached 1 pulse/h within 6 h. Thereafter, pulse frequency increased marginally and reached 1 pulse/50 min by the onset of the LH surge. This pattern was not affected by previous treatment with bFF. In the control ewes, the amplitude of the LH pulses did not change significantly following luteolysis or at any time during the follicular phase, while the levels of FSH declined slowly until the onset of the surge. In the treated ewes, on the other hand, there was an immediate increase in both LH pulse amplitude and the concentration of FSH immediately after the end of bFF treatment at luteolysis, and they remained above control levels for 24 and 16 h respectively. Plasma prolactin levels did not appear to change around the time of luteolysis but showed a marked and significant diurnal rhythm (nadir around noon and peak around midnight) in both groups. The concentrations of prolactin were significantly (P<0·001) lower and the preovulatory peak was delayed and reduced in the bFF-treated ewes relative to controls. The onset of oestrus was also significantly (P<0·01) delayed by bFF treatment, but the ovulation rates did not differ between the groups. Furthermore, comparisons within or between groups revealed no significant relationships between any of the variables of plasma LH secretion during the follicular phase and the subsequent ovulation rate. These observations provide a complete description of gonadotrophin patterns during the follicular phase of the ewe and confirm the suggestion that an increase in LH pulse frequency is the major driving force behind the follicular growth that ultimately leads to ovulation. On the other hand, it appears most unlikely that the pattern of LH secretion during the follicular phase has any influence on ovulation rate. The levels of FSH declined in the period leading up to the preovulatory surge, presumably as a consequence of rising peripheral levels of oestrogen (and/or inhibin). We also expected LH pulse amplitude to decline during the follicular phase because it has been proposed that pulse amplitude is also controlled by oestrogen. The absence of any significant fall in amplitude suggests that hypotheses about the control of LH secretion drawn from studies with ovariectomized ewes require further verification in the intact ewe. The effect of bFF on prolactin levels probably reflects the low rates of secretion of oestradiol by the small ovarian follicles in these ewes. J. Endocr. (1988) 116, 123–135

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