Compensation by pulsatile GnRH infusions for incompetence for oestradiol-induced LH surges in long-term ovariectomized gilts and castrated male pigs.

The aim of this study was to investigate incompetence for oestradiol-induced LH surges in long-term ovariectomized gilts and male pigs. Gilts (250 days old; n = 36), which had been ovariectomized 30 (OVX 30) or 100 days (OVX 100) before the start of treatment, were challenged i.m. with oestradiol benzoate and were either given no further treatment, fed methallibure to inhibit endogenous GnRH release or fed methallibure and given i.v. pulses of 100 or 200 ng GnRH agonist at 1 h intervals during the LH surge (48-96 h after oestradiol benzoate). The same treatments were applied to long-term orchidectomized male pigs (ORC, n = 23). In addition, one ORC group was not injected with oestradiol benzoate but was fed methallibure and given pulses of 200 ng GnRH agonist. Oestradiol benzoate alone induced an LH surge in the OVX 30 group only (5/6 gilts), methallibure suppressed (P < 0.05) oestradiol benzoate-induced LH secretion, while pulses of 100 ng GnRH agonist in animals fed methallibure produced LH surges in four of six OVX 30 and four of six OVX 100 gilts. The induced LH surges were similar to those produced by oestradiol benzoate alone in OVX 30 gilts. Pulses of 200 ng GnRH agonist produced LH surges in OVX 30 (6/6) and OVX 100 (6/6) gilts and increased the magnitude of the induced LH surge in OVX 100 gilts (P < 0.05 compared with 100 ng GnRH agonist or OVX 30 control). Pulses of 200 ng GnRH agonist also induced LH surge release in ORC male pigs (5/6), but were unable to increase LH concentrations in a surge-like manner in ORC animals that had not been given oestradiol benzoate, indicating that oestradiol increases pituitary responsiveness to GnRH. These results support the hypothesis that oestradiol must inhibit secretion of LH before an LH surge can occur. It is concluded that incompetence for oestradiol-induced LH surges in long-term ovarian secretion-deprived gilts and in male pigs is due to the failure of oestradiol to promote a sufficient increase in the release of GnRH.     

Effect of adrenocorticotrophic hormone (ACTH1-24) on ovine pituitary gland responsiveness to exogenous pulsatile GnRH and oestradiol-induced LH release in vivo.

The present experiment was designed to determine if and how exogenous ACTH replicates the effects of stressors to delay the preovulatory LH surge in sheep. Twenty-four hours after oestrous synchronisation with prostaglandin in the breeding season, groups of 8-9 intact ewes were injected with 50 microg oestradiol benzoate (0 h) followed 8 h later by 3 injections of saline or GnRH (500 ng each, i.v.) at 2 h intervals (controls). Two further groups received an additional 'late' injection of ACTH (0.8 mg i.m.) 7.5 h after oestradiol, i.e., 0.5 h before the first saline or GnRH challenge. To examine if the duration of prior exposure to ACTH was important, another group of ewes was given ACTH 'early', i.e. 2.5 h before the first GnRH injection. The first GnRH injection produced a maximum LH response of 1.9+/-0.4 ng/ml which was significantly (p < 0.01) enhanced after the second and third GnRH challenge (7.1+/-1.5 ng/ml and 7.0+/-1.7 ng/ml, respectively; 'self-priming'). Late ACTH did not affect the LH response after the first GnRH challenge (1.9+/-0.4 vs. 1.8+/-0.3 ng/ml; p > 0.05) but decreased maximum LH concentrations after the second GnRH to 35% (7.1+/-1.5 vs. 4.6+/-1.1 ng/ml; p = 0.07) and to 40% after the third GnRH (7.0+/-1.7 vs. 4.0+/-0.8 ng/ml; p = 0.05). When ACTH was given early, 4.5 h before the second GnRH, there was no effect on this LH response suggesting that the effect decreases with time after ACTH administration. Concerning the oestradiol-induced LH surge, exogenous GnRH alone delayed the onset time (20.5+/-2.0 vs. 27.8+/-2.1 h; p > 0.05) and reduced the duration of the surge (8.5+/-0.9 vs. 6.7+/-0.6 h; p > 0.05). The onset of the LH surge was observed within 40 h after oestradiol on 29 out of 34 occasions in the saline +/- GnRH treated ewes compared to 11 out of 34 occasions (p < 0.05) when ACTH was also given, either late or early. In those ewes that did not have an LH surge by the end of sampling, plasma progesterone concentrations during the following oestrous cycle increased 2 days later suggesting a delay, not a complete blockade of the LH surge. In conclusion, we have revealed for the first time that ACTH reduces the GnRH self-priming effect in vivo and delays the LH surge, at least partially by direct effects at the pituitary gland.     

Effect of endogenous and exogenous progesterone on the oestradiol-induced LH surge in dairy cows

Four cows released an LH surge after 1.0 mg oestradiol benzoate administered i.m. during the post-partum anoestrous period with continuing low plasma progesterone. A similar response occurred in the early follicular phase when plasma progesterone concentration at the time of injection was less than 0.5 ng/ml. Cows treated with a progesterone-releasing intravaginal device (PRID) for 8 days were injected with cloprostenol on the 5th day to remove any endogenous source of progesterone. Oestradiol was injected on the 7th day when the plasma progesterone concentration from the PRID was between 0.7 and 1.5 ng/ml. No LH surge occurred. Similarly, oestradiol benzoate injected in the luteal phase of 3 cows (0.9-2.1 ng progesterone/ml plasma) did not provoke an LH surge. An oestradiol challenge given to 3 cows 6 days after ovariectomy induced a normal LH surge in each cow. However, when oestradiol treatment was repeated on the 7th day of PRID treatment, none released LH. It is concluded that ovaries are not necessary for progesterone to inhibit the release of LH, and cows with plasma progesterone concentrations greater than 0.5 ng/ml, whether endogenous or exogenous, did not release LH in response to oestradiol.     

Synchronous fluctuations of LH and FSH in plasma samples collected daily during the estrous cycle in mares

Circulating concentrations of LH and FSH in each of 12 mares were measured in daily blood samples from 3 d before until 3 d after an interovulatory interval (ovulation=Day 0). The interval was normalized to its mean length (22 d) and partitioned into periods relative to high and low (first significant increase and decrease: Days 3 and 14, respectively) mean FSH concentrations. The resulting experimental periods were as follows: 1) Days −3 to 2 corresponding to the periovulatory period, 2) Days 3 to 14 corresponding to the luteal period, and 3) Days −7 to 3 corresponding to the follicular-periovulatory period. An adaptive threshold method was used to detect peak concentrations of LH and FSH fluctuations. There was no significant difference in the number of detected LH fluctuations per mare among the 3 periods (means, 1.2, 1.8, 1.6 fluctuations, respectively). However, more (P<0.05) FSH fluctuations per mare were detected during the luteal period (mean, 2.4 fluctuations) than during the periovulatory period (mean, 0.5 fluctuations) and follicular-periovulatory period (mean, 1.2 fluctuations). Synchronous LH and FSH fluctuations, defined as the simultaneous detection of peak concentrations of fluctuations, occurred more (P<0.05) often per mare during the luteal period (mean, 1.3 fluctuations) than during the periovulatory period (mean, 0.1 fluctuations) and follicular-periovulatory period (mean, 0.2 fluctuations). During the luteal period, concentrations of LH peaked (P<0.05) during FSH fluctuations and, conversely, concentrations of FSH peaked (P<0.05) during LH fluctuations, indicating a high degree of coupling between the 2 gonadotropins. In summary, fluctuations of LH and FSH occurred in synchrony with a high degree of coupling between them during the luteal period, but not during the periovulatory and follicular-periovulatory periods.     

Endurance exercise potentiates the stimulatory influence of oestrogen-progesterone on LH and FSH release in the rat

Ovariectomized rats were treated with oestradiol benzoate and progesterone or GnRH. Prolonged exercise (running 4 days per week for 6 weeks) markedly potentiated the oestrogen/progesterone-induced release of LH and FSH, but the pituitary response to an injection of GnRH was unaffected. In contrast, at 24 h after a single exercise bout there was no apparent effect on steroid and GnRH stimulated LH and FSH responses although an acute exercise session given on the day of the LH surge inhibited steroid-induced LH release in some rats. We conclude that strenuous, prolonged exercise-training in the ovariectomized rat seems to modify the ability of the hypothalamus to release GnRH. The results were not attributable to a single bout of exercise since the gonadotrophin responses immediately or 24 h after such exercise did not parallel the results observed in the trained rats.     

Induction of follicular development and ovulation in seasonally acyclic mares using gonadotrophin-releasing hormones and progesterone.

Deeply acyclic (seasonally anovulatory) mares were treated with GnRH or a GnRH analogue to induce follicular development and ovulation. Courses of GnRH (3--4) were administered at approximately 10-day intervals to reproduce the gonadotrophin surges which precede ovulation in the normal cycle. Exogenous progesterone was administered in an attempt to reproduce the luteal phase pattern. Induced serum FSH concentrations were comparable to those causing follicular development in the normal cycle, but induced LH levels were lower and of shorter duration than those of the periovulatory surge. Three of 4 mares treated with GnRH appeared to ovulate, but did not establish CL. Nine of 10 mares given GnRH analogue also developed follicles during the final treatment course, as did mares treated with progesterone only, while only 1 of 5 untreated control mares showed any ovarian development. Failure to induce final follicular maturation and CL development by this treatment regimen may be due to an inadequate LH surge at the time of the expected ovulation associated with the low preovulatory oestradiol-17 beta surge, possibly caused by the preceding FSH stimulation being inadequate or inappropriate. Progesterone treatment increased baseline FSH concentrations in GnRH-treated mares, and also stimulated follicular development in mares not treated with GnRH, indicating a possible role for progesterone in folliculogenesis and, indirectly, ovulation.     

Effect of progesterone, administered via intravaginal rings, on serum concentrations of oestradiol, FSH, LH and prolactin in women

Intravaginal rings containing progesterone were inserted on Day 5 of the cycle to 8 healthy, normally menstruating women. Blood samples were taken during Days 4--22 of the cycle at 2--3-day intervals. The plasma progesterone levels obtained after the insertion were between 7.5 and 21 nmol/l. Four subjects showed no increase in plasma oestradiol concentrations. The subjects showing increased plasma oestradiol levels also showed a positive feedback on LH, resulting in ovulation or an LH peak. The results suggest that progesterone may have a local inhibitory effect on the follicular oestradiol production.     

Oestradiol administration raises luteal LH receptor levels in intact and hysterectomized pigs

Occupied and unoccupied LH receptors in corpora lutea, and LH and progesterone concentrations in circulating plasma, were measured in non-pregnant gilts that had been treated with oestradiol-17 beta benzoate to prolong luteal function. Oestradiol benzoate (5 mg, administered on Day 12 after oestrus) delayed luteal regression and the decline in LH receptor levels at luteolysis and raised unoccupied receptor levels from 11.8 +/- 1.14 fmol/mg protein on Days 10--15 after oestrus to 31.8 +/- 3.26 fmol/mg protein on Days 15--21. There was no simultaneous rise in occupied receptor levels and occupancy decreased from 29.8 +/- 3.01 to 11.5 +/- 1.26%. Basal plasma LH concentrations were unchanged by oestradiol, but mean corpus luteum weight and plasma progesterone concentrations were slightly reduced. Oestradiol benzoate on Day 12 caused a similar increase in unoccupied receptor levels in gilts hysterectomized on Days 6--9 after oestrus, from 17.0 +/- 5.83 to 34.5 +/- 6.00 fmol/mg protein, determined on Days 15--18. Plasma concentrations of LH and progesterone were unchanged by oestradiol. Unoccupied receptor levels in corpora lutea and plasma LH and progesterone were unaltered by hysterectomy in untreated gilts. Occupied receptor levels were not influenced by hysterectomy or oestradiol. It is concluded that oestradiol-17 beta raises luteal LH receptor levels by a mechanism independent of the uterus.     

The acute effects of oestradiol-17beta and synthetic LH-RH on plasma LH levels in freemartin heifers.

Injection of oestradiol was followed by a surge of plasma LH within 24 h in only 7 of 12 freemartins. Elevations of plasma LH were less than those reported for normal non-cyclic heifers, but some freemartins showed a delayed, or more prolonged, LH response. Responsiveness to oestradiol was not related to degree of chimaerism or plasma androstenedione level, and most of the animals responded similarly in two trials carried out 4 months apart, during which time plasma androstenedione levels had more than doubled. Freemartins which showed an LH surge after oestradiol treatment released greater amounts of LH after the injection of LH-RH than did non-responders.     

Progesterone pretreatment has a direct effect on GnRH-induced preovulatory follicles to determine their ability to develop into normal corpora lutea in anoestrous ewes

In two experiments carried out during seasonal anoestrus, Romney Marsh ewes were treated with small-dose (250 ng) multiple injections of GnRH at 2-h intervals with and without progesterone pretreatment. In Exp. 1, 8/8 progesterone-primed ewes ovulated and produced functionally normal corpora lutea compared with 2/9 non-primed ewes. Follicles were recovered from similarly treated animals 18 or 28 h after the start of GnRH treatment (at least 14 h before the estimated time of the LH peak) and assessed in terms of diameter, granulosa cell number, oestradiol, testosterone and progesterone concentrations in the follicular fluid, oestradiol production in vitro and binding of 125I-labelled hCG to granulosa and theca. There were no significant differences in any of these measures in 'ovulatory' follicles recovered from the progesterone-pretreated compared to non-pretreated animals. In Exp. 2, follicles were removed from similar treatment groups just before and 2 h after the start of the LH surge. Unlike 'ovulatory' follicles recovered from the non-pretreated ewes, those recovered from progesterone-pretreated ewes responded to the LH surge by significantly increasing oestradiol secretion (P less than 0.01) and binding of 125I-labelled hCG (P less than 0.05) to granulosa cells. Overall there was also more (P less than 0.05) hCG binding to granulosa and theca cells from progesterone-pretreated animals. Non-ovulatory follicles recovered from progesterone-primed ewes had more (P less than 0.05) binding of 125I-labelled hCG to theca and a higher testosterone concentration in follicular fluid (P less than 0.05) than did those from non-primed ewes. These results suggest that inadequate luteal function after repeated injections of GnRH may be due to a poor response to the LH surge indicative of a deficiency in the final maturational stages of the follicle.     

Sustained but not repeated acute elevation of cortisol impaired the luteinizing hormone surge, estrus, and ovulation in gilts.

We tested the hypothesis that sustained and repeated acute elevation of cortisol would impair the LH surge, estrus, and ovulation in gilts. Cortisol was injected intramuscularly, to achieve a sustained elevation of plasma concentrations of cortisol, or intravenously, to achieve an acute elevation of plasma concentrations of cortisol. Control gilts received i.m. injections of oil and i.v. injections of saline. These treatments were administered to gilts (n = 6 per treatment) at 12-h intervals from Days 7 to 11 of the estrous cycle until after estrus ceased or until Day 27 or 28 of the estrous cycle, whichever came first. The repeated acute elevation of cortisol had no effect on the LH surge, estrus, or ovulation. In contrast, when the elevation of cortisol was sustained, the LH surge, estrus, and ovulation were inhibited. We conclude that cortisol is capable of direct actions to impair reproductive processes in female pigs but that plasma concentrations of cortisol need to be elevated for a substantial period for this to occur.     

Effect of betamethasone treatment on luteal lifespan and the LH response to GnRH in dairy cows

Betamethasone (a synthetic glucocorticoid, 15 mg) was administered i.m. twice daily for 10 days to 4 regularly cycling dairy cows, beginning on Day 10 of the oestrous cycle. Luteal function, monitored by plasma progesterone, was extended by 7, 9, 19 and 20 days, respectively. Luteal function in the next cycle was normal. Endogenous cortisol values were suppressed for 14, 13, 34 and 27 days, respectively. Pituitary responsiveness to 20 micrograms GnRH was assessed by LH measurement on Days -1, +3 and +7 relative to the start of betamethasone treatment. There was a progressive decrease in peak LH concentrations after each GnRH challenge compared to control cows. Hourly measurements of PGF-2 alpha metabolite during the expected period of luteolysis failed to reveal normal increases. It is suggested that betamethasone caused prolonged luteal function, either by directly inhibiting PGF-2 alpha release, or by suppressing pituitary stimulation of follicular growth and hence lowering oestradiol concentrations, since it is known that PGF-2 alpha and oestradiol act synergistically to cause luteolysis.     

Pituitary and ovarian hormone secretion and ovulation in gilts injected with gonadotropins during and after oral administration of progesterone agonist (Altrenogest)

We determined changes in plasma hormone concentrations in gilts after treatment with a progesterone agonist, Altrenogest (AT), and determined the effect of exogenous gonadotropins on ovulation and plasma hormone concentrations during AT treatment. Twenty-nine cyclic gilts were fed 20 mg of AT/(day X gilt) once daily for 15 days starting on Days 10 to 14 of their estrous cycle. The 16th day after starting AT was designated Day 1. In Experiment 1, the preovulatory luteinizing hormone (LH) surge occurred 5.6 days after cessation of AT feeding. Plasma follicle-stimulating hormone (FSH) increased simultaneously with the LH surge and then increased further to a maximum 2 to 3 days later. In Experiment 2, each of 23 gilts was assigned to one of the following treatment groups: 1) no additional AT or injections, n = 4; 2) no additional AT, 1200 IU of pregnant mare's serum gonadotropin (PMSG) on Day 1, n = 4); 3) AT continued through Day 10 and PMSG on Day 1, n = 5, 4) AT continued through Day 10, PMSG on Day 1, and 500 IU of human chorionic gonadotropin (hCG) on Day 5, n = 5; or 5) AT continued through Day 10 and no injections, n = 5. Gilts were bled once daily on Days 1-3 and 9-11, bled twice daily on Days 4-8, and killed on Day 11 to recover ovaries. Termination of AT feeding or injection of PMSG increased plasma estrogen and decreased plasma FSH between Day 1 and Day 4; plasma estrogen profiles did not differ significantly among groups after injection of PMSG (Groups 2-4). Feeding AT blocked estrus, the LH surge, and ovulation after injection of PMSG (Group 3); hCG on Day 5 following PMSG on Day 1 caused ovulation (Group 4). Although AT did not block the action of PMSG and hCG at the ovary, AT did block the mechanisms by which estrogen triggers the preovulatory LH surge and estrus.     

An alteration in the hypothalamic action of estradiol due to lack of progesterone exposure can cause follicular cysts in cattle

Many mammals, including cattle, can develop ovarian follicular cysts, but the physiological mechanisms leading to this condition remain undefined. We hypothesized that follicular cysts can develop because estradiol will induce a GnRH/LH surge on one occasion but progesterone exposure is required before another GnRH/LH surge can be induced by estradiol. In experiment 1, 14 cows were synchronized with an intravaginal progesterone insert (IPI) for 7 days, and prostaglandin F(2alpha) was given on the day of IPI removal. Estradiol benzoate (EB; 5 mg i.m.) was given 3 days before IPI removal to induce atresia of follicles. Cows were given a second EB treatment 1 day after IPI removal to induce a GnRH/LH surge in the absence of an ovulatory follicle. All cows had an LH surge following the second EB treatment, and 10 of 14 cows developed a large-follicle anovulatory condition (LFAC) that resembled follicular cysts. These LFAC cows were given a third EB treatment 15 days later, and none of the cows had an LH surge or ovulation. Cows were then either not treated (control, n = 5) or treated for 7 days with an IPI (n = 5) starting 7 days after the third EB injection. Cows were treated for a fourth time with 5 mg of EB 12 h after IPI removal. All IPI-treated, but no control, cows had an LH surge and ovulated in response to the estradiol challenge. In experiment 2, cows were induced to LFAC as in experiment 1 and were then randomly assigned to one of four treatments 1) IPI + EB, 2) IPI + GnRH (100 microg), 3) control + EB, and 4) control + GnRH. Control and IPI-treated cows had a similar LH surge and ovulation when treated with GnRH. In contrast, only IPI-treated cows had an LH surge following EB treatment. Thus, an initial GnRH/LH surge can be induced with high estradiol, but estradiol induction of a subsequent GnRH/LH surge requires exposure to progesterone. This effect is mediated by the hypothalamus, as evidenced by similar LH release in response to exogenous GnRH. This may represent the physiological condition that underlies ovarian follicular cysts.     

Episodic LH secretion patterns in the mare during the oestrous cycle.

Jugular blood samples were obtained from 8 mares at 5- and/or 20-min intervals for 2 to 5 days during various phases of the oestrous cycle for plasma LH determination. An episodic release pattern was observed in 1 of 3 mares sampled during the ovulatory period. One mare had one secretory burst and the other mare had several periods of fluctuating plasma LH concentration. During dioestrus, episodic secretions were observed in 2 mares sampled 11 to 13 days before and, in 1 mare, 9 days after ovulation. During the 2 to 5-day period before ovulation, episodic secretion was not observed (3 mares) but plasma LH concentrations fluctuated as much as 6 ng/ml during a period of 3--4 h. Daily plasma samples were obtained form 10 mares (1--8 oestrous cycles/mare) during which 22 single, 18 double and 2 luteal-phase ovulations occurred. Dioestrous ovulations were accompanied by small increases in plasma LH (1--4 ng/ml), but many similar increases in LH were not accompanied by ovulation. No significant differences in secretory patterns were observed between single and multiple ovulations. In one mare, 4 ovulations occurred in the presence of a prolonged luteal phase; 3 were accompanied by increasing LH concentrations and the other occurred when LH was at a low concentration.     

Changes in pulsatile LH secretion and the positive and negative feedback actions of oestradiol after administration of a GnRH agonist in the ovariectomized ewe

Administration of a GnRH agonist (5 micrograms) every 12 h to long-term ovariectomized ewes for 5 or 10 days during the breeding season suppressed mean LH levels from around 6 to 1 ng/ml on Days 1 and 4 after treatment; on Day 1 after treatment LH pulse frequency and amplitude were lower than pretreatment values. On Day 4 after treatment LH pulse frequency was restored to pretreatment levels (1 per h) whereas LH pulse amplitude had only slightly increased from 0.5 to 1 ng/ml, a value 25% of that before treatment. This increase in amplitude was greater the shorter the duration of treatment. Ovariectomized ewes treated with the agonist for 5 days exhibited both negative and positive feedback actions after implantation of a capsule containing oestradiol; however, compared to control ewes treated with oestradiol only, the positive and negative feedback actions of oestradiol were blunted. These results suggest that the recovery of tonic LH concentrations after GnRH agonist-induced suppression is limited primarily by changes in LH pulse amplitude. The results also demonstrate that the feedback actions of oestradiol are attenuated, but not blocked, by GnRH agonist treatment.     

Direct effect of prolactin, induced by TRH injection, on ovarian oestradiol secretion in the ewe

The effect of sustained high plasma levels of prolactin, induced by repeated 2-h i.v. injections of thyrotrophin-releasing hormone (TRH; 20 micrograms), on ovarian oestradiol secretion and plasma levels of LH and FSH was investigated during the preovulatory period in the ewe. Plasma levels of progesterone declined at the same rate after prostaglandin-induced luteal regression in control and TRH-treated ewes. However, TRH treatment resulted in a significant increase in plasma levels of LH and FSH compared to controls from 12 h after luteal regression until 5 to 6 h before the start of the preovulatory surge of LH. In spite of this, and a similar increase in pulse frequency of LH in control and TRH-treated ewes, ovarian oestradiol secretion was significantly suppressed in TRH-treated ewes compared to that in control ewes. The preovulatory surge of LH and FSH, the second FSH peak and subsequent luteal function in terms of plasma levels of progesterone were not significantly different between control and TRH-treated ewes. These results show that TRH treatment, presumably by maintaining elevated plasma levels of prolactin, results in suppression of oestradiol secretion by a direct effect on the ovary in the ewe.     

Pulsatile GnRH administration stimulates the number of pituitary GnRH receptors in seasonally anoestrous ewes

Twenty seasonally anoestrous ewes were pretreated with progesterone for 4 days and divided into four equal groups. Ewes in Group 1 received no GnRH treatment and were slaughtered immediately after progesterone removal. Ewes in Groups 2, 3 and 4 received i.v. injections of 250 ng GnRH every 2 h for 36 h starting at the time of progesterone removal. Ewes in Group 2 were slaughtered immediately after the 36 h GnRH pulsing, while ewes in Groups 3 and 4 were given a bolus injection of 125 micrograms GnRH at this time and were slaughtered 2 and 10 h after the bolus injection, respectively. Blood samples were collected every 30 min from ewes in Group 4 only, from 4 h before the start of GnRH treatment until 10 h after the bolus injection. Pulsing with GnRH resulted in episodic release of LH, and the bolus injection of GnRH was immediately followed by a preovulatory type LH surge in those ewes in which an endogenous surge had no already begun. The pituitary GnRH receptor numbers were significantly higher for the ewes in Group 2 than for any of the other treatment groups, while there was no significant difference in the receptor numbers between Groups 1, 3 and 4. The results suggest an up-regulation of GnRH receptors resulting from pulsatile GnRH therapy.     

Regulation of circulating gonadotropins by the negative effects of ovarian hormones in mares

The functional and temporal relationships between circulating gonadotropins and ovarian hormones in mares during Days 7-27 (ovulation = Day 0) was studied using control, follicle ablation, and ovariectomy groups (n = 6 mares/group). In the follicle-ablation group, all follicles > or = 6 mm were ablated on Day 7, and every 2 days thereafter, newly emerging follicles were also ablated. Estradiol concentrations decreased (P < 0.01) similarly in the controls and the follicle-ablation group between Days 7 and 11 and by Day 15 began to increase in the controls and continued to decrease in the follicle-ablation group. Concentrations of progesterone were not affected by follicle ablation, but diameter of the corpus luteum was greater (P < 0.05) by Day 21 in the follicle-ablation group; these results indicated that the follicles were involved in morphologic luteolysis, but not in functional luteolysis. Concentrations of LH were higher (P < 0.05) on Days 15 and 16 in the follicle-ablation group than in the controls, indicating an initial negative effect of follicles on LH. Immunoreactive inhibin and estradiol decreased (P < 0.0001) and FSH and LH increased (P < 0.05) within 1 or 2 days after ovariectomy; these changes occurred more slowly in the follicle-ablation group. The maximum value for an FSH surge in each control mare was below the lower 95% confidence limit in the ovariectomy group. Maximum concentration for the periovulatory LH surge in the controls was not different from the mean maximum LH concentrations in the ovariectomy group. Our interpretation is that the gonadotropin surges resulted from changes in the magnitude of the negative effects of ovarian hormones on the positive effects of extraovarian control. There was no indication of a positive ovarian effect on either FSH or LH.     

FSH and LH concentrations in periparturient mares.

The influence of the ovaries and presence of a foal on periparturient concentrations of FSH and LH were studied in 19 Pony mares. In intact and ovariectomized mares, mean concentrations of FSH fluctuated between 1.1and 9.9 ng/ml on Days -14 to-1 before parturition (Day 0). A surge of FSH occurred in all mares in association with parturition. From Days 1 to 10, the high levels of FSH gradually decreased in the intact group to the minimal concentrations that occur during oestrus, but remained elevated in the ovariectomized mares. There were no significant pre-partum changes in LH in either type of mare. Post-partum changes in LH concentrations increased at a similar rate in ovariectomized and intact mares. The presence of a foal significantly lengthened the interval to first oestrus, depressed LH levels on Days 6--10 and decreased the FSH concentrations as averaged over the 10 days before the first ovulation after parturition.