RU486 blocks the secondary surge of follicle-stimulating hormone in the rat without blocking the drop in serum inhibin.

The stimulatory effect of progesterone on the release of the primary surges of serum LH and FSH is well characterized. Less is known about the relationship of progesterone to the secondary FSH surge. We used the antiprogesterone, RU486, to block the action of progesterone and studied the effects on the primary surges of LH and FSH, and especially on the secondary surge of FSH. Proestrous rats were treated with RU486 at 1,200 h. Rats were killed on proestrus and estrus, and serum levels of LH, FSH, and inhibin were measured. In all RU486-treated rats, the primary surges of LH and FSH were significantly attenuated, and the secondary FSH surge was completely abolished, despite a drop in inhibin levels following the primary surges. A high replacement dose of progesterone, delivered immediately after RU486 treatment, did not restore the primary surges of LH and FSH, or the secondary surge of FSH. These data suggest that other factors in addition to a drop in inhibin are responsible for producing the secondary FSH surge.     

Interaction between ovarian and adrenal steroids in the regulation of gonadotropin secretion

Recent work from our laboratory suggests that a complex interaction exists between ovarian and adrenal steroids in the regulation of preovulatory gonadotropin secretion. Ovarian estradiol serves to set the neutral trigger for the preovulatory gonadotropin surge, while progesterone from both the adrenal and the ovary serves to (1) initiate, (2) synchronize, (3) potentiate and (4) limit the preovulatory LH surge to a single day. Administration of RU486 or the progesterone synthesis inhibitor, trilostane, on proestrous morning attenuated the preovulatory LH surge. Adrenal progesterone appears to play a role in potentiating the LH surge since RU486 still effectively decreased the LH surge even in animals ovariectomized at 0800 h on proestrus. The administration of ACTH to estrogen-primed ovariectomized (ovx) immature rats caused a LH and FSH surge 6 h later, demonstrating that upon proper stimulation, the adrenal can induce gonadotropin surges. The effect was specific for ACTH, required estrogen priming, and was blocked by adrenalectomy or RU486, but not by ovariectomy. Certain corticosteroids, most notably deoxycorticosterone and triamcinolone acetonide, were found to possess "progestin-like" activity in the induction of LH and FSH surges in estrogen-primed ovx rats. In contrast, corticosterone and dexamethasone caused a preferential release of FSH, but not LH. Progesterone-induced surges of LH and FSH appear to require an intact N-methyl-D-aspartate (NMDA) neurotransmission line, since administration of the NMDA receptor antagonist, MK801, blocked the ability of progesterone to induce LH and FSH surges. Similarly, NMDA neurotransmission appears to be a critical component in the expression of the preovulatory gonadotropin surge since administration of MK801 during the critical period significantly diminished the LH and PRL surge in the cycling adult rat. FSH levels were lowered by MK801 treatment, but the effect was not statistically significant. The progesterone-induced gonadotropin surge appears to also involve mediation through NPY and catecholamine systems. Immediately preceding the onset of the LH and FSH surge in progesterone-treated estrogen-primed ovx. rats, there was a significant elevation of MBH and POA GnRH and NPY levels, which was followed by a significant fall at the onset of the LH surge. The effect of progesterone on inducing LH and FSH surges also appears to involve alpha 1 and alpha 2 adrenergic neuron activation since prazosin and yohimbine (alpha 1 and 2 blockers, respectively) but not propranolol (a beta-blocker) abolished the ability of progesterone to induce LH and FSH surges. Progesterone also caused a dose-dependent decrease in occupied nuclear estradiol receptors in the pituitary.(ABSTRACT TRUNCATED AT 400 WORDS)     

Plasma gonadotrophin responses in beef cows two progesterone plus prostaglandin treatment

Progesterone Releasing Intravaginal Devices (Prids) were inserted into six post-partum beef cows for nine days and 0.5 mg cloprostenol was injected i m on day eight. Blood samples were taken via jugular venous catheters at frequent intervals for seven days after Prid removal and assayed for LH, FSH and progesterone. The induced pre-ovulatory type LH and FSH surges occurred between 35 and 123h after Prid withdrawal in five of the cows. In four cows which underwent surges during the time of most intensive sampling, LH levels were significantly higher during the 30h period prior to the LH surge than during the 30h period after the surge. FSH values were low for the 30h period preceding and the 14h period following the time of maximum FSH/LH concentrations. 16 - 30h after the FSH and LH surges, FSH values were again significantly raised compared with the period immediately after the surge. Despite the success of this Prid/PG regime in inducing ovulation, the variability in time between progestagen withdrawal and the LH surge and ovulation is such that the use of fixed time artificial insemination may give poor results.     

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.     

Detailed examination of the mechanism and site of action of progesterone and corticosteroids in the regulation of gonadotropin secretion: hypothalamic gonadotropin-releasing hormone and catecholamine involvement.

Progesterone and certain corticosteroids, such as deoxycorticosterone (DOC) and triamcinolone acetonide (TA), can stimulate gonadotropin surges in rats. The mechanism of these steroids could involve a pituitary or hypothalamic site of action, or both. Progesterone and TA did not alter the ability of GnRH to release LH or FSH either before, during, or after the gonadotropin surge induced by these steroids in estrogen-primed ovariectomized female rats. Furthermore, progesterone, TA and DOC were unable to induce a gonadotropin surge in short-term estrogen-primed castrated male rats. These results suggested a hypothalamic rather than a pituitary site of action of progesterone and corticosteroids in the release of gonadotropins. Since progestin and corticosteroid receptors are present in catecholamine neurons, a role for catecholamine neurotransmission in progesterone and corticosteroid-induced surges of LH and FSH in estrogen-primed ovariectomized rats was examined. Catecholamine synthesis inhibitors and specific alpha 1 (prazosin), alpha 2 (yohimbine), and beta (propranolol) receptor antagonists were used to determine the role of catecholamine neurotransmission in the steroid-induced surges of LH and FSH. Both of the catecholamine synthesis inhibitors, alpha-methyl-p-tyrosine HCl (alpha-MPT), a tyrosine hydroxylase inhibitor, and sodium diethyldithiocarbamate (DDC), an inhibitor of dopamine-beta-hydroxylase, attenuated the ability of progesterone, TA, and DOC to induce LH surges when administered 3 h and 1 h, respectively, before the steroid. DDC also suppressed the ability of progesterone, TA, and DOC to induce FSH surges. Rats treated with alpha-MPT had lower mean FSH values than did steroid controls, but the effect was not significant. Both the alpha 1 and alpha 2 adrenergic antagonists, prazosin and yohimbine, significantly suppressed the ability of progesterone, TA, and DOC to induce LH and FSH surges. In contrast, the beta adrenergic receptor blocker, propranolol, had no effect upon the ability of progesterone, TA, or DOC to facilitate LH and FSH secretion. Finally, the stimulatory effect of progesterone and TA upon LH and FSH release was found to be blocked by prior treatment with a GnRH antagonist, further suggesting hypothalamic involvement. In conclusion, this study provides evidence that the stimulation of gonadotropin release by progesterone and corticosteroids is mediated through a common mechanism, and that this mechanism involves the release of GnRH, most likely through catecholaminergic stimulation. Furthermore, catecholamine neurotransmission, through alpha 1 and alpha 2 but not beta receptor sites, is required for the expression of progesterone and corticosteroid-induced surges of LH and FSH in estrogen-primed ovariectomized rats.     

Resumption of gonadotrophin release during the post-partum period in suckling and non-suckling ewes

The post-partum secretion of LH, FSH and prolactin was monitored in 15 suckling and 6 non-suckling Préalpes du Sud ewes lambing during the breeding season by measuring plasma hormone concentrations daily at 6-h intervals and also weekly at 20-min intervals for 6 h from parturition to resumption of regular cyclic ovarian activity. There was a constant phenomenon in the resumption of normal patterns of FSH and LH secretion: there was a rise in FSH values culminating on average on Day 4 post partum and returning subsequently to values observed during the oestrous cycle, and concurrently an increase in the frequency and amplitude of LH pulses more progressive in suckling than in non-suckling ewes which led to an elevation of LH mean concentrations and occurrence of an LH surge. Since neither the FSH secretory pattern nor FSH mean values differed between suckling and non-suckling ewes, the results suggested that LH pulsatile pattern was a major limiting factor for the resumption of normal oestrous cycles. Before regular oestrous cycles resumed other changes in preovulatory LH surges also occurred: (i) they increased in duration and probably in amplitude; (ii) they were preceded by an acceleration in LH pulse frequency and a large decrease in FSH values as in normal cyclic ewes; and (iii) at least in non-suckling ewes they occurred concurrently with a prolactin surge.     

The influence of estradiol-17beta and progesterone on peripheral serum concentrations of luteinizing hormone and follicle stimulating hormone in the ovariectomized ewe

Serum gonadotropin concentrations were high and variable and fluctuated episodically in short and long term ovariectomized ewes. Treatment with solid silastic implants releasing progesterone (serum levels 1.81 +/- 0.16 ng/ml) had no consistent effect. Treatment with implants releasing estradiol-17beta significantly depressed mean serum gonadotropin concentrations and peak height to values usually seen in intact ewes. This occurred regardless of implant size and serum estradiol-17beta concentrations (range 11 +/- 0.3 pg/ml to 98 +/- 12.8 pg/ml). Progesterone and estradiol-17beta together significantly depressed the frequency of peaks in LH concentration. Following progesterone removal, 95% of the ewes treated with progesterone and estradiol-17beta implants experienced a transient increase in serum LH concentrations similar to the preovulatory surge in intact ewes. Eighty-four percent of the LH surges were accompanied by a surge in serum FSH concentrations. However, following progesterone removal, 5.1 +/- 2.1 FSH surges were observed over six days. Gonadotropin surges occurred regardless of estradiol-17beta implant size and with or without the influence of supplemental estradiol-17beta.     

Effects of bovine follicular fluid inhibin on serum gonadotrophin concentrations in ewes during oestrus

Experiments were conducted with ewes to investigate the effects of an enriched bovine follicular fluid inhibin preparation (INH) on gonadotrophin secretion after the onset of oestrus. Administration of INH (10 mg) 1 h after the onset of oestrus did not significantly alter the preovulatory FSH and LH surges or the second FSH peak. To determine the effects of INH on the second FSH surge, ewes were treated with saline (N = 7) or INH (N = 10) at 4 h (10 mg) and 24 h (5 mg) after the peak of the preovulatory LH surge. The second FSH surge was delayed about 24 h (P less than 0.05) in ewes treated with INH; however, the delay did not alter the interval to the next oestrus. In a third experiment, 16 ewes were assigned to 4 groups in a 2 x 2 factorial with the main effects being ovariectomy at 4 h and INH treatment (10 mg) at 4, 20 and 36 h after the peak of the LH surge. Controls received sham ovariectomy and saline injection as appropriate. Ovariectomy resulted in a rapid increase in serum FSH but not LH and this was delayed (P less than 0.05) by INH treatment. These results indicate that inhibin has a selective inhibitory action on FSH secretion in ewes and suggests that the second FSH surge results from increased basal FSH secretion due to decreased endogenous inhibin levels.     

Temporal relations between plasma concentrations of luteinizing hormone, follicle-stimulating hormone, estradiol-17beta, progesterone, prolactin, and alpha-melanocyte-stimulating hormone during the follicular, ovulatory, and early luteal phase in the bitch

Compared with other domestic animals, relatively little is known about the changes in, and temporal relations between, reproductive hormones around the time of ovulation in the domestic bitch. Therefore, plasma concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol-17beta, progesterone, prolactin (PRL), and alpha-melanocyte-stimulating hormone (alpha-MSH) were determined one to six times daily from the start of the follicular phase until 5 days after the estimated day of ovulation in six Beagle bitches. In all bitches, the pre-ovulatory LH surge was accompanied by a pre-ovulatory FSH surge. A pre-ovulatory PRL or alpha-MSH surge was not observed. The pre-ovulatory FSH and LH surges started concomitantly in four bitches, but in two bitches the FSH surge started 12 h earlier than the LH surge. The FSH surge (110+/-8 h) lasted significantly longer than the LH surge (36+/-5 h). In contrast with the pre-ovulatory FSH surge, the pre-ovulatory LH surge was bifurcated in four of six bitches. The mean plasma LH concentrations before (1.9+/-0.4 microg/L) and after (1.9+/-0.3 microg/L) the LH surge were similar, but the mean plasma FSH concentration before the FSH surge (1.6+/-0.3 U/L) was significantly lower than that after the FSH surge (3.1+/-0.2 U/L). In most bitches the highest plasma estradiol-17beta concentration coincided with or followed the start of the pre-ovulatory LH surge. In five of the six bitches the plasma progesterone concentration started to rise just before or concurrently with the start of the LH surge. In conclusion, the results of this study provide evidence for the differential regulation of the secretion of LH and FSH in the bitch. In addition, the interrelationship of the plasma profiles of estradiol-17beta and LH suggests a positive feedback effect of estradiol-17beta on LH surge release. The start of the pre-ovulatory LH surge is associated with an increase in the plasma progesterone concentration in this species.     

Fetal programming: testosterone exposure of the female sheep during midgestation disrupts the dynamics of its adult gonadotropin secretion during the periovulatory period

Prenatal exposure of the female sheep to excess testosterone (T) leads to hypergonadotropism, multifollicular ovaries, and progressive loss of reproductive cycles. We have determined that prenatal T treatment delays the latency of the estradiol (E2)-induced LH surge. To extend this finding into a natural physiological context, the present study was conducted to determine if the malprogrammed surge mechanism alters the reproductive cycle. Specifically, we wished to determine if prenatal T treatment 1) delays the onset of the preovulatory gonadotropin surge during the natural follicular phase rise in E2, 2) alters pulsatile LH secretion and the dynamics of the secondary FSH surge, and 3) compromises the ensuing luteal function. Females prenatally T-treated from Day 60 to Day 90 of gestation (147 days is term) and control females were studied when they were approximately 2.5 yr of age. Reproductive cycles of control and prenatally T-treated females were synchronized with PGF2alpha, and peripheral blood samples were collected every 2 h for 120 h to characterize cyclic changes in E2, LH, and FSH and then daily for 14 days to monitor changes in luteal progesterone. To assess LH pulse patterns, blood samples were also collected frequently (each 5 min for 6 h) during the follicular and luteal phases of the cycle. The results revealed that, in prenatally T-treated females, 1) the preovulatory increase in E2 was normal; 2) the latencies between the preovulatory increase in E2 and the peaks of the primary LH and FSH surges were longer, but the magnitudes similar; 3) follicular-phase LH pulse frequency was increased; 4) the interval between the primary and secondary FSH surges was reduced but there was a tendency for an increase in duration of the secondary FSH surge; but 5) luteal progesterone patterns were in general unaltered. Thus, exposure of the female to excess T before birth produces perturbances and maltiming in periovulatory gonadotropin secretory dynamics, but these do not produce apparent defects in cycle regularity or luteal function. To reveal the pathologies that lead to the eventual subfertility arising from excess T exposure during midgestation, studies at older ages must be conducted to assess if there is progressive disruption of neuroendocrine and ovarian function.     

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.     

Hormone secretion in the asian elephant (Elephas maximus): characterization of ovulatory and anovulatory luteinizing hormone surges.

In the elephant, two distinct LH surges occur 3 wk apart during the nonluteal phase of the estrous cycle, but only the second surge (ovLH) induces ovulation. The function of the first, anovulatory surge (anLH) is unknown, nor is it clear what regulates the timing of these two surges. To further study this observation in the Asian elephant, serum concentrations of LH, FSH, progesterone, inhibin, estradiol, and prolactin were quantified throughout the estrous cycle to establish temporal hormonal relationships. To examine long-term dynamics of hormone secretion, analyses were conducted in weekly blood samples collected from 3 Asian elephants for up to 3 yr. To determine whether differences existed in secretory patterns between the anLH and ovLH surges, daily blood samples were analyzed from 21 nonluteal-phase periods from 7 Asian elephants. During the nonluteal phase, serum LH was elevated for 1-2 days during anLH and ovLH surges with no differences in peak concentration between the two surges. The anLH surge occurred 19.9+/-1.2 days after the end of the luteal phase and was followed by the ovLH surge 20.8+/-0.5 days later. Serum FSH concentrations were highest at the beginning of the nonluteal phase and gradually declined to nadir concentrations within 4 days of the ovLH surge. FSH remained low until after the ovLH surge and then increased during the luteal phase. Serum inhibin concentrations were negatively correlated with FSH during the nonluteal phase (r = -0.53). Concentrations of estradiol and prolactin fluctuated throughout the estrous cycle with no discernible patterns evident. In sum, there were no clear differences in associated hormone secretory patterns between the anLH and ovLH surge. However, elevated FSH at the beginning of the nonluteal phase may be important for follicle recruitment, with the first anLH surge acting to complete the follicle selection process before ovulation.     

Oestradiol and the preovulatory surges of luteinising hormone and follicle stimulating hormone in ewes during the breeding season and transition into anoestrus

This study was designed to see if giving exogenous oestradiol, during the follicular phase of the oestrous cycle of intact ewes, during the breeding season or transition into anoestrus, would alter the occurrence, timing or magnitude of the preovulatory surge of secretion of luteinising hormone (LH) or follicle stimulating hormone (FSH). During the breeding season and the time of transition, separate groups of ewes were infused (intravenously) with either saline (30 ml h⁻¹; n = 6) or oestradiol in saline (n = 6) for 30 h. Infusion started 12 h after removal of progestin-containing intravaginal sponges that had been in place for 12 days. The initial dose of oestradiol was 0.02 μg h⁻¹; this was doubled every 4 h for 20 h, followed by every 5 h up to 30 h, to reach a maximum of 1.5 μg h⁻¹. Following progestin removal during the breeding season, peak serum concentrations of oestradiol in control ewes were 10.31 ± 1.04 pg ml⁻¹, at 49.60 ± 3.40 h after progestin removal. There was no obvious peak during transition, but at a time after progestin removal equivalent to the time of the oestradiol peak in ewes at mid breeding season, oestradiol concentrations were 6.70 ± 1.14 pg ml⁻¹ in ewes in transition (P < 0.05). In oestradiol treated ewes, peak serum oestradiol concentrations (24.8 ± 2.1 pg ml⁻¹) and time to peak (41.00 ± 0.05 h) did not differ between seasons (P > 0.05). During the breeding season, all six control ewes and four of six ewes given oestradiol showed oestrus with LH and FSH surges. The two ewes not showing oestrus did not respond to oestrus synchronisation and had persistently high serum concentrations of progesterone. During transition, three of six control ewes showed oestrus but only two had LH and FSH surges; all oestradiol treated ewes showed oestrus and gonadotrophin surges (P < 0.05). The timing and magnitude of LH and FSH surges did not vary with treatment or season. In blood samples collected every 12 min for 6 h, from 12 h after the start of oestradiol infusion, mean serum concentrations of LH and LH pulse frequency were lower in control ewes during transition than during mid breeding season (P < 0.05). Oestradiol treatment resulted in lower mean serum concentrations of LH in season and lower LH pulse frequency in transition (P < 0.05). We concluded that enhancing the height of the preovulatory peak in serum concentrations of oestradiol during the breeding season did not alter the timing or the magnitude of the preovulatory surge of LH and FSH secretion and that at transition into anoestrus, oestradiol can induce oestrus and the surge release of LH and FSH as effectively as during the breeding season.     

Gonadotrophin secretion during the periovulatory period in Galway and Finnish Landrace ewes and Finnish Landrace ewes selected for high ovulation rate

Rates of ovulation differed significantly (P less than 0.01) among ewes of the different genetic lines. However, of the reproductive characteristics studied, only progesterone concentration at the height of luteal function, duration of oestrus, and interval from onset of oestrus to peak of the preovulatory gonadotrophin surge showed significant positive association with rate of ovulation. The pattern of secretion of LH during the periovulatory period did not differ in the Galway and Finnish Landrace breeds. The total amount of LH secreted during the preovulatory surge did not differ amongst lines. Similarly, no difference in the plasma concentration of LH at the height of the preovulatory surge was noted among Galway and reference Finnish Landrace lines. However, the concentration of LH at the height of the surge was significantly (P less than 0.05) reduced in the selected Finnish Landrace line. Plasma concentrations of FSH during the preovulatory period were significantly (P less than 0.05) elevated in the breed (Galway) with the lowest prolifcacy. When contrasted with either of the Finnish Landrace lines, the magnitudes of the preovulatory surge of FSH and the secondary surge of FSH were significantly greater (P less than 0.05) in Galway ewes. These results suggest that genetic difference in rate of ovulation among sheep breeds is not tightly coupled to quantitative differences in plasma concentration of gonadotrophic hormones during the periovulatory period.     

Reproductive endocrine effects of intranasal administration of norethisterone to adult female rhesus monkeys (Macaca mulatta)

Intranasal administration of norethisterone at a daily dose of 9 micrograms between Days 5 and 14 of the menstrual cycles blocked ovulation in 10 out of 17 adult female monkeys. Serum concentrations of hormones indicated that ovulation was blocked due to a suppression of the mid-cycle, oestradiol-induced LH surge. Ovarian follicular activity in the treated menstrual cycles was not affected by norethisterone but there was a marked delay in the onset of the mid-cycle oestradiol surge in most of the treated animals. The duration of the menstrual cycle length after the oestradiol peak was significantly reduced in all the treated monkeys, indicative of a shortened luteal phase.     

Estradiol induces and progesterone inhibits the preovulatory surges of luteinizing hormone and follicle-stimulating hormone in heifers

Objectives were to determine: 1) whether estradiol, given via implants in amounts to stimulate a proestrus increase, induces preovulatory-like luteinizing hormone (LH) and follicle-stimulating hormone (FSH) surges; and 2) whether progesterone, given via infusion in amounts to simulate concentrations found in blood during the luteal phase of the estrous cycle, inhibits gonadotropin surges. All heifers were in the luteal phase of an estrous cycle when ovariectomized. Replacement therapy with estradiol and progesterone was started immediately after ovariectomy to mimic luteal phase concentrations of these steroids. Average estradiol (pg/ml) and progesterone (ng/ml) resulting from this replacement were 2.5 and 6.2 respectively; these values were similar (P greater than 0.05) to those on the day before ovariectomy (2.3 and 7.2, respectively). Nevertheless, basal concentrations of LH and FSH increased from 0.7 and 43 ng/ml before ovariectomy to 2.6 and 96 ng/ml, respectively, 24 h after ovariectomy. This may indicate that other ovarian factors are required to maintain low baselines of LH and FSH. Beginning 24 h after ovariectomy, replacement of steroids were adjusted as follows: 1) progesterone infusion was terminated and 2 additional estradiol implants were given every 12 h for 36 h (n = 5); 2) progesterone infusion was maintained and 2 additional estradiol implants were given every 12 h for 36 h (n = 3); or 3) progesterone infusion was terminated and 2 additional empty implants were given every 12 h for 36 h (n = 6). When estradiol implants were given every 12 h for 36 h, estradiol levels increased in plasma to 5 to 7 pg/ml, which resembles the increase in estradiol that occurs at proestrus. After ending progesterone infusion, levels of progesterone in plasma decreased to less than 1 ng/ml by 8 h. Preovulatory-like LH and FSH surges were induced only when progesterone infusion was stopped and additional estradiol implants were given. These surges were synchronous, occurring 61.8 +/- 0.4 h (mean +/- SE) after ending infusion of progesterone. We conclude that estradiol, at concentrations which simulate those found during proestrus, induces preovulatory-like LH and FSH surges in heifers and that progesterone, at concentrations found during the luteal phase of the estrous cycle, inhibits estradiol-induced gonadotropin surges. Furthermore, ovarian factors other than estradiol and progesterone may be required to maintain basal concentrations of LH and FSH in heifers.     

Inhibitory effect of progesterone in the postcastration gonadotrophin rise in women

This study was designed to investigate the effects of progesterone on the gonadotrophin rise after bilateral salpingo-oophorectomy (BSO). Twenty-eight regularly menstruating women underwent hysterectomy and BSO during the follicular phase of the menstrual cycle. They were divided into 5 groups depending on the treatment after BSO. Plasma LH and FSH were studied serially for 14 days after BSO and the patterns of LH and FSH rises were contrasted to those observed in the control group which received neither progesterone nor estrogen. LH and FSH levels in the group which were given low dose progesterone only, rose consistently after BSO and these patterns were similar to those seen in the control group. However, the addition of estrogen reduced gonadotrophin rises significantly more than estrogen did alone. Further, the luteal phase level of progesterone solely has a suppressive effect on the gonadotrophin rises after BSO. Our observations suggest that synergism of progesterone with estrogen may exist in suppressing gonadotrophin secretion in the normal luteal phase and should help in understanding why gonadotrophin levels in the luteal phase are lower than those in the follicular phase of the menstrual cycle.     

Effects of estradiol on gonadotropin subunit messenger ribonucleic acid amounts during an induced gonadotropin surge in anestrous ewes

The preovulatory gonadotropin surge in the sheep was recently characterized by a divergent pattern of LH beta and FSH beta mRNAs immediately preceding this event. It is not clear whether this pattern is due to estradiol (E2), inhibin or other effectors. In this study, to determine if E2 may be involved in the divergent beta mRNA patterns seen during the surge, gonadotropin surges were induced in anestrous ewes (An) by E2 (An + E2) and several parameters were then measured. These included the amounts of alpha, LH beta, and FSH beta mRNAs, as assessed by solution hybridization assays, plus pituitary and serum gonadotropin concentrations. The values were compared with those observed in control, An ewes, to assess the effect of E2. The E2 treatment resulted in LH and FSH surges that appeared to be similar to the normal surges seen during the breeding season. Concomitantly, the E2 treatment lowered pituitary concentrations of FSH (P less than 0.05), while LH amounts did not change. Although the effect of E2 on gonadotropin subunit mRNA amounts varied depending upon the individual subunit, the changes that were observed paralleled changes reported during the preovulatory surge of the cycle. Specifically, alpha mRNA amounts increased significantly (P less than 0.001) while FSH beta mRNA amounts fell dramatically (P less than 0.001). Moreover, LH beta mRNA amounts were slightly increased, although not significantly by E2. These results demonstrate that E2 effects changes in the amounts of the gonadotropin subunit mRNAs during an induced gonadotropin surge in An ewes.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.