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1.
Ciliary neurotropic factor (CNTF) is a neuroregulatory cytokine belonging to the interleukin-6 type cytokine superfamily. Although a few studies have reported a facilitatory action of CNTF on the reproductive axis in rodents, information along this line is still very limited. In this study, we examined a possible role of CNTF in the generation of ovarian steroid-induced luteinizing hormone (LH) and prolactin (PRL) surges in the rat, a crucial physiological event in mammalian reproduction. Experiments were performed on both normally-fed and 3-day-fasted rats, ovariectomized and primed with estradiol and progesterone. Blood was collected every 30 min between 11:00 and 18:00 h, to measure LH and PRL. Drugs were given intracerebroventricularly at 11:00 h. Compared to control serum, undiluted as well as threefold dilutions of anti-CNTF serum caused partial but significant suppression of LH surges. Both concentrations of the antibody also delayed the onset of PRL surge to a comparable degree. Fasted rats did not exhibit significant surges of the hormones, while 0.3 and 1.0 nmol, but not 0.1 nmol, recombinant human CNTF led to a dose-dependent recovery of both LH and PRL surges. These results demonstrate for the first time a significant role of CNTF in the generation of preovulatory LH and PRL surges in the rat. CNTF may thus be another humoral signal linking nutrition and reproductive function. 相似文献
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3.
Neuropeptide Y gene expression in the arcuate nucleus is increased during preovulatory luteinizing hormone surges. 总被引:2,自引:0,他引:2
Recent studies have suggested that neuropeptide Y (NPY) plays an important role in the induction of the preovulatory LH surge. The present study was performed in order to determine if a change in NPY gene expression within arcuate nucleus NPY neurons is associated with the generation of the preovulatory LH surge. In Exp 1, in situ hybridization was used to measure NPY messenger RNA (mRNA) levels in the arcuate nucleus of female rats at 0900 h and every 2 h from 1400-2200 h on the day of proestrus (PRO). Comparisons between groups showed a clear, stepwise increase in NPY gene expression throughout the day of PRO. At 1600 h, when LH values were significantly greater than 0900 h values, NPY mRNA labeling intensities in the arcuate nucleus were significantly greater than 0900 h levels (P < 0.01). By 1800 h, the time at which the LH surge peaked, NPY mRNA levels also peaked and were nearly 3-fold greater than levels observed at 0900 h (P < 0.01). NPY mRNA levels at 2000 h and 2200 h remained elevated above 0900 h levels (P < 0.01) but by 2000 h had decreased significantly from 1800 h levels (P < 0.05). In Exp 2, NPY mRNA levels were measured once again at 0900 h and 1800 h on PRO, and then at 0900 h and 1800 h on metestrus (MET), in order to determine if the change in gene expression seen in Exp 1 was unique to the day of PRO, or if it simply reflected a daily rhythm of gene expression in the nucleus. Analysis of mRNA levels showed no difference in NPY mRNA levels between 0900-1800 h on MET. Also, NPY mRNA levels at 0900 h and 1800 h on MET were significantly less than levels at 1800 h on PRO (P < 0.01). These results are consistent with the hypothesis that NPY neurons participate in the generation of LH surges through increased production of NPY and subsequent potentiation of the release and/or actions of LHRH. 相似文献
4.
We recently demonstrated that neuropeptide Y (NPY) potentiates the ability of pulsatile LHRH infusions to restore LH surges in pentobarbital (PB)-blocked, proestrous rats. In the present study we determined if specific endocrine conditions are necessary for the expression of these direct pituitary effects of NPY. Facilitatory actions of NPY were examined in the absence of gonadal feedback [ovariectomy (OVX)], in the presence of negative gonadal feedback (metestrus), after estrogen priming of the pituitary gland [OVX plus 30 micrograms estradiol benzoate (EB) 2 days before experiments], and after treatments which evoke preovulatory-like LH surges (OVX plus EB and 5 mg progesterone or P the morning of experiments). Rats received jugular catheter implants the day before experiments. On the day of experiments, hourly blood samples were taken from 1100-2100 h. At 1330 h, rats received injections of PB to block endogenous LHRH release, or saline. Every 30 min from 1400-1800 h, PB-treated rats received iv pulses of LHRH (15 ng/pulse) or saline, along with concurrent pulses of NPY (1 or 5 micrograms/pulse) or saline. Plasma samples were analyzed by LH RIA. In all cases, pulsatile administration of 15 ng LHRH resulted in plasma LH levels that were significantly elevated above saline-treated, PB-blocked controls. Only in the case of EB+P-treated rats did coadministration of 5 micrograms NPY along with LHRH significantly enhance LHRH-stimulated LH secretion (P < 0.001). NPY had no effect on LHRH-stimulated LH secretion in OVX, OVX + EB-treated, or metestrous rats. Pulsatile administration of either dose of NPY alone did not stimulate LH release in any of the four groups examined. These results demonstrate that the facilitatory effects of NPY on LHRH-stimulated LH secretion can be manifest only under the endocrine conditions required to produce full, preovulatory-like LH surges, i.e. after estrogen and P treatment. 相似文献
5.
Effects of immobilization stress on estrogen-induced surges of luteinizing hormone and prolactin in ovariectomized rats 总被引:6,自引:0,他引:6
Reproductive function has been known to be impaired by various kinds of physical and emotional stress, but the mechanism by
which stress impairs the reproductive axis has not been clearly understood. In the present study, the effects of immobilization
stress were studied on the surges of luteinizing hormone (LH) and prolactin (PRL) induced by 17β-estradiol (E2) in ovariectomized rats. Two weeks after bilateral ovariectomy, animals were implanted with the capsule containing E2 or vehicle at 1000 h (designated as d 0). Immobilization was started at 1000 h and continued to 2100 h on d 2. Blood samples
were collected according to the time schedule by a jugular vein catheter procedure. Immobilization stress inhibited basal
release of LH and abolished E2-induced LH and PRL surges in ovariectomized (OVX) rats. Daily repeated immobilization (from 1200 h to 1800 h, 6 h/d) for
3 d also abolished LH and PRL surges when examined at 1800 h on d 2. Although daily repeated immobilization stress reduced
E2-induced PRL mRNA levels, this stress failed to change LHβ mRNA levels in the anterior pituitary as determined by Northern
blot analysis. Gonadotropin-releasing hormone (GnRH) receptor mRNA levels in the anterior pituitary were lowered by immobilization
stress in the OVX, E2-treated group. Dopamine D2 receptor mRNA levels in the anterior pituitary of OVX, E2-treated rats were significantly decreased at 1800 h, compared with those at 1000 h. However, immobilization prevented a decrease
in dopamine D2 receptor mRNA levels at 1800 h. GnRH content was increased in the mediobasal hypothalamus by immobilization
in the OVX, E2-treated group, suggesting that GnRH release was inhibited. Interestingly, GnRH mRNA levels in the preoptic area-anterior
hypothalamic area were suppressed by immobilization stress in OVX, E2-treated rats when determined at 1800 h. Therefore, we concluded that immobilization stress blocks E2-induced LH surge possibly by inhibiting synthesis and release of GnRH at the hypothalamic level, and an increase of dopaminergic
activity via D2 receptor at the pituitary level might be involved in the stress blockage of E2-induced PRL surge. 相似文献
6.
Differential alterations in dopamine turnover rates in the stalk-median eminence and posterior pituitary during the preovulatory prolactin surge 总被引:1,自引:0,他引:1
The relative contributions of dopamine (DA) and prolactin-releasing factor (PRF) in generating the preovulatory prolactin (PRL) surge were investigated. Immature female rats were injected with pregnant mare's serum gonadotropin (PMSG) on day 28. Jugular blood was collected hourly on days 30 and 31. PRL levels were low in the morning of day 30, rose 10-12 times to peak levels from 14.00 to 16.00 h, reached a prolonged plateau from 18.00 to 24.00 h, and reduced to basal levels in the morning of day 31. All PMSG-treated rats ovulated an average of 13-14 ova. PRL levels in age-matched control rats were low throughout this time, and no oviductal ova were present. DA turnover rates in the stalk-median eminence (SME) and posterior pituitary (PP) were determined from the decline in tissue DA after injecting alpha-methyl-p-tyrosine (alpha-MPT), a competitive inhibitor of tyrosine hydroxylase. DA turnover rates increased or were unaltered in the SME and PP, respectively, during the peak PRL phase as compared to presurge rates. In contrast, DA turnover rates were significantly reduced in both tissues during the plateau phase. The turnover rate in the SME, but not the PP, was increased in the morning of day 31. DA turnover rates in control rats never changed. Injection of alpha-MPT to PMSG-treated rats increased PRL levels at all times examined except during the plateau phase. Blood PRL levels were also determined in PMSG-treated rats following posterior pituitary lobectomy or sham lobectomy. The PRL surge was similar in both groups and all rats ovulated.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
7.
In vivo release of prolactin-releasing peptide in rat hypothalamus in association with luteinizing hormone and prolactin surges. 总被引:6,自引:0,他引:6
H Watanobe 《Neuroendocrinology》2001,74(6):359-366
Prolactin (PRL)-releasing peptide (PrRP) is a novel hypothalamic peptide reported to be a potent and specific stimulator of PRL secretion. This author recently reported that PrRP might play a significant role in mediating the steroid-induced PRL surge in the rat. In order to examine the secretory profile of PrRP in the rat hypothalamus before and during the luteinizing hormone (LH) and PRL surges, this study employed the push-pull perfusion technique and determined the in vivo release of PrRP and also of gonadotropin-releasing hormone (GnRH) in ovariectomized rats primed with estradiol and progesterone. In the medial preoptic area (MPOA) where the GnRH neuronal perikarya exist, GnRH release was increased prior to the initiation of the LH surge, and PrRP also started rising even earlier than GnRH. In the median eminence-arcuate nucleus complex (ME-ARC), where GnRH neuronal fibers terminate, GnRH secretion started increasing before the commencement of the LH surge, but the release of PrRP did not change significantly. These results suggest that PrRP may play a role in mediating the steroid-induced LH surge by activating GnRH neurons in the MPOA. A possible involvement of PrRP in the PRL surge was not suggested from the present data. The lack of a significant alteration in PrRP release in the ME-ARC may argue against a direct hypophysiotropic action of the peptide. 相似文献
8.
J Saini C Simon G Brandenberger G Wittersheim M Follenius 《Journal of endocrinological investigation》1992,15(10):741-747
The two hypothalamic releasing factors, luteinizing hormone releasing hormone (LHRH) and thyrotropin releasing hormone (TRH), have been shown to stimulate pituitary prolactin (PRL) release as well as their respective pituitary hormones, luteinizing hormone (LH) and thyrotropin (TSH). In this study the influence of LH and TSH regulatory mechanisms on nocturnal PRL secretion was investigated by evaluating whether the coincidence of PRL with LH and TSH pulses occurred more frequently than would be expected if the hormone generators were not coupled. Thirty night studies were conducted in twelve healthy male subjects. Six subjects underwent 3 studies and 6 subjects 2 studies. Blood was collected into aliquots at 10 min intervals throughout the night and plasma concentrations of PRL, TSH, and LH were determined. From the plasma profiles, hormone secretory rates were calculated using a method of deconvolution. Significant plasma and secretory hormone pulses were identified by a peak detection computer program. For statistical analysis the night studies of each subject were concatenated. Concomitance between the plasma pulses of both TSH and LH with PRL was insufficient to reject the null hypothesis of random coincidence. An increase in the number of subjects demonstrating significant coincidence between the hormone pulses was obtained when secretory pulses were analysed. Seven of the 12 and 10 of the 12 subjects showed significant concomitance between PRL and respectively TSH and LH. This proportion was sufficient to confirm copulsatility between PRL and LH. These results suggest that LH regulatory mechanisms are involved in the generation of the nocturnal pulsatile PRL profile, TRH may also play a role in the secretion of PRL at a central level, but was not reflected in the plasma or secretory profiles because of other overriding regulatory factors. 相似文献
9.
Sex differences in gonadal function are driven by either cyclical (females) or tonic (males) hypothalamic GnRH1 release and, subsequently, gonadotrophin (LH and FSH) secretion from the pituitary. This sex difference seems to depend on the perinatal actions of gonadal hormones on the hypothalamus. We used alpha-fetoprotein (AFP) knockout mice (Afp(-/-)) to study the mechanisms by which estrogens affect the sexual differentiation of the GnRH1 system. Afp(-/-) mice lack the protective actions of AFP against estrogens circulating during embryonic development, leading to infertility probably due to a hypothalamic dysfunction. Therefore, we first determined whether Afp(-/-) females are capable of showing a steroid-induced preovulatory LH surge by FOS/GnRH1 immunohistochemistry and RIA of plasma LH levels. Because the KISS1/GPR54 system is a key upstream regulator of the GnRH1 system as well as being sexually dimorphic, we also analyzed whether Kisspeptin-10 neurons were activated in Afp(-/-) mice after treatment with estradiol and progesterone. We found that the GnRH1 and Kisspeptin-10 neuronal systems are defeminized in Afp(-/-) females because they did not show either steroid-induced LH surges or significant FOS/GnRH1 double labeling. Furthermore, Kisspeptin-10 immunoreactivity and neural activation, measured by the number of double-labeled FOS/Kisspeptin-10 cells, were lower in Afp(-/-) females, suggesting a down-regulation of GnRH1 function. Thus, the sex difference in the ability to show preovulatory LH surges depends on the prenatal actions of estrogens in the male hypothalamus and, thus, is lost in Afp(-/-) females because they lack AFP to protect them against the defeminizing effects of estrogens during prenatal development. 相似文献
10.
M Selmanoff 《Endocrinology》1981,108(5):1716-1722
In the adult male rat, we have succeeded in microdissecting the median eminence into a LHRH-rich lateral region (MEl) and a LHRH-poor medial region (MEm). Dissected in this manner, the MEm has a 4.8-fold lower LHRH concentration and a 1.5-fold higher DA concentration than the MEl. The concentration of norepinephrine (NE) is not different in the two regions. Estimates of the rate constants for dopamine (DA) and NE decay after synthesis inhibition revealed no significant differences between the MEl and MEm kinetics for either amine. Hyperprolactinemia, produced by ovine PRL administration, resulted in marked increases in DA turnover rates in both the MEm (2.7-fold) and the MEl (4.7-fold). These effects of PRL were specific to the tuberoinfundibular DA neurons, as DA turnover was unaffected in nigrostriatal, mesolimbic, and incertohypothalamic DA neurons, and no changes were observed in NE turnover in any study area. The results support the involvement of PRL in the short loop feedback regulation of its own secretion in the MEm. The data further demonstrate a hypothalamic mechanism in the MEl by which hyperprolactinemia could inhibit LHRH release. 相似文献
11.
The frequency of preovulatory luteinizing hormone (LH) surges is an important determinant of ovulation and oviposition rates in turkeys. Egg production rate is relatively poor in heavy weight-sire line type turkey hens and declines with advancing duration of the reproductive period. The purpose of this study was to measure frequency and characteristics of preovulatory LH surges in turkey hens of a heavy weight-sire line type early, at peak of egg production (Early), and late, after egg production rate had declined (Late), in a reproductive period. The Early hens were photostimulated with a continuous photoperiod [24 h light (L):0 h dark (D)] at 40 weeks of age and sampled during peak egg production at about 47 weeks of age. The Late hens were photostimulated at 40 weeks of age with a long day photoperiod (14L:10D). After a 27-week egg production period, the Late hens were switched to the 24L:0D photoperiod and sampled at 74 weeks of age. Continuous lighting was used during blood sampling to allow the rhythm of preovulatory LH surges to free run. All hens were cannulated 3-5 days before starting sampling and hourly blood samples were collected for 200 h. All hens were necropsied and ovarian and oviductal morphologies were measured after serial bleeding. The Late hens had a longer interval between intra-clutch preovulatory LH surges than the Early hens, and a higher incidence of atretic ovarian follicles. The Early hens had higher baseline and surge amplitude LH concentrations but lower progesterone (P4) surge amplitude concentrations than the Late hens. The duration of preovulatory LH surges, incidence of "blind" preovulatory LH surges, baseline P4 concentrations, and overall estradiol-17beta (E2) concentrations were not different between Early and Late hens. In conclusion, a longer interval between preovulatory LH surges, lower LH baseline and surge amplitude concentrations, a higher incidence of atretic follicles, and higher P4 surge amplitude concentration were associated with the decline in egg production late in the reproductive period in a heavy weight-sire line of turkey hens. 相似文献
12.
The present study investigated the role of hypothalamic VIP in the regulation of the LH and PRL surge using immunoneutralization of endogenous VIP in mature ovariectomized (OVX), estradiol benzoate (EB)-treated female Wistar rats. We compared the effect of intracerebroventricular (i.c.v.) injections of a VIP antiserum (VIP-Ab) with that of saline (Ctr) on LH and PRL profiles in two separate groups of rats following two subcutaneous EB injections on days 8 and 9 after OVX. VIP-Ab or Ctr injections were given during the second half of the dark period, i.e. at 22:00 h (day 9), and, in addition, the following morning, i.e. at 08:00 h (day 10), just before the expected onset of the LH surge. Hourly blood samples were collected between 09:00 and 18:00 h on day 10. In addition, we studied the reproducibility of EB-induced LH and PRL surges and compared the effect of Ctr and VIP-Ab treatment on sequential surges in individual OVX females, i.e. 10 and 23 days after OVX, using each animal as its own control. Although we observeda large variation in the height and timing of LH and PRL peak levels between EB-treated females, the characteristics of successive surges of individual rats were highly reproducible. This reproducibility suggests that differences in functioning of the suprachiasmatic nucleus as well as in the response of the hypothalamus to steroid feedback largely explain the normal variation in hormone responses between rats. The VIP-Ab treatment resulted in a significant delay in the time course and a strong reduction of the magnitude of the afternoon LH and PRL surge. When analyzed within individual females, the effect of VIP-Ab treatment was even more pronounced due to a reduction in variability when each animal was used as its own control. These results suggest that hypothalamic VIP is an important regulator of both the timing and the magnitude of the EB-induced LH and PRL surge in the OVX rat, and suggest that its role may be stimulatory in this respect. 相似文献
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Cycling rats injected with 2-hydroxyestrone or 2-hydroxyestradiol at 09.00 or 10.00 h in the morning of proestrus do not express the normal preovulatory LH surge in the afternoon of the day. The LHRH content of the median eminence in control animals decreases sharply in the afternoon from elevated noon and morning levels. The catechol estrogen-treated rats fail to show the decrease. Thus the catechol estrogens block the LH surge at its usual time by influencing the changes in the concentration of LHRH in the median eminence on proestrus. Since the catechol estrogens have short biological half-lives, their effect on the LHRH content in the afternoon must originate in the morning at the time of the endogenous estradiol (E2) peak. These results have implications in the physiological processes responsible for the positive feedback of estradiol on the preovulatory LH surge in the rat. 相似文献
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C M March U Goebelsmann R M Nakamura D R Mishell 《The Journal of clinical endocrinology and metabolism》1979,49(4):507-513
The positive feedback effects of estradiol (E2) and progesterone (P) on LH and FSH release were studied under novel experimental conditions in three women of reproductive age who had undergone oophorectomy and received uninterupted E2 replacement by subdermal implants. Basal serum E2 levels were in the midfollicular phase range, while LH and FSH levels were normal or slightly elevated. Each volunteer underwent seven experiments at 2- to 4-week intervals, receiving im injections of increasing amounts of estradiol benzoate (E2B) alone and in combination with P. The time and dose of P (administered via P-impregnated polysiloxane intravaginal rings) were varied. In two of the seven experiments, P was given without E2B injections. In all three subjects, increasing serum E2 levels mimicking the preovulatory E2 peak were followed by a surge of LH but not of FSH. However, when serum P levels rose after an increase in serum E2 concentrations had occurred, the LH surge occurred earlier and was accompanied by an FSH peak. When serum P levels rose before serum E2 concentrations had risen or when P levels increased without a rise in serum E2, neither a serum LH nor FSH peak was observed. When administered concomitantly, E2B and P suppressed FSH but not LH levels, while P alone did not affect serum LH or FSH concentrations. These data indicate that an acute rise in serum E2 is a necessary condition for the midcycle LH and FSH surges, that P facilitates or blocks the positive feedback response of gonadotropin release in a time-dependent manner, and that P is required for the preovulatory FSH peak. 相似文献
15.
Relation between luteinizing hormone and prolactin pulses in ovariectomized rats with or without dopamine inhibition 总被引:1,自引:0,他引:1
GnRH and GnRH-associated peptide (GAP) have been shown to be cosecreted as spontaneous pulses in hypophysial portal blood. In addition, GAP has been proposed as a physiological inhibitor of PRL secretion. The present investigation was performed to determine whether GAP might play a role in the moment to moment regulation of PRL release in the ovariectomized rat. We anticipated that an inverse relation might exist between PRL and LH pulses if GAP is a physiological regulator of PRL and is coreleased with GnRH. Serial blood samples were collected at 6-min intervals over 4 h from ovariectomized rats bearing chronic jugular catheters and were analyzed for plasma concentrations of PRL and LH by RIA. Release patterns were assessed using a pulse detection algorithm. Some animals were pretreated 30 min before blood sampling with domperidone (a dopamine antagonist that does not cross the blood-brain barrier) to unmask PRL inhibitory responses to GAP that might not otherwise be observable in the presence of normal dopamine inhibition. PRL secretory patterns were pulsatile but highly irregular, in contrast to the regular rhythmic patterns of circulating LH. Domperidone treatment significantly increased the number of PRL pulses. PRL pulse amplitudes, and mean PRL concentrations compared to those in vehicle-injected controls. LH pulses after domperidone administration were more frequent, resulting in slightly higher mean LH concentrations. In both vehicle- and domperidone-injected rats, 60-80% of PRL pulses were concordant with LH pulses (concordance defined as PRL and LH peaks occurring within one sample of each other). Assuming that GAP is cosecreted with GnRH, these data fail to support an acute physiological role for GAP during undisturbed PRL release in the ovariectomized rat because the expected relation between PRL and LH pulses in the event of such a role was not observed. To test a role for GAP more directly, domperidone-treated rats were injected with a rabbit anti-GAP serum during serial blood collection. No increase in PRL release was elicited by this treatment, and pulsatile PRL and LH secretion were unaffected compared to those in control animals injected with hyperimmune serum. To determine whether GnRH is the PRL-releasing secretagogue responsible for concordant PRL and LH pulses, some rats were pretreated 4 h before blood sampling with a potent GnRH antagonist, followed by domperidone 30 min before sampling. Treatment with GnRH antagonist virtually abolished LH pulses, but had no effect on PRL pulses.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
16.
Streptozotocin-diabetic rats suffered growth failure and had reduced serum levels of the acid--ethanol soluble component of non-suppressible insulin-like activity (NSILA-S) compared with normal rats. Chronic insulin substitution (6 weeks) resulted in a normalization of serum levels of NSILA-S; this was accompanied by a normal increase in weight. Insulin therapy for 3 days resulted in a partial recovery of serum levels of NSILA-S and a slight but significant accompanying gain in weight. Short-term administration of GH also resulted in a partial recovery of the serum level of NSILA-S, in spite of continued uncontrolled diabetes. These results demonstrate that, in the rat, insulin as well as GH contributes to the regulation of serum levels of NSILA-S. 相似文献
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O Giampietro G Moggi R Chisci A Coluccia A D Luche N Simonini I Brunori 《The Journal of clinical endocrinology and metabolism》1979,49(1):141-143
We studied PRL, FSH, and LH response to LRH in 82 anovulatory and 4 normally ovulating women. Ten anovulatory patients who were basally hyperprolactinemic showed no significant change in PRL concentration after LRH. Of the remaining 72 anovulatory patients with basal PRL levels in the normal range, 59 showed no PRL modification after LRH (as in normals) whereas in 13 patients, a prompt and significant rise of PRL concentration above basal levels in response to LRH was observed. In these 13 patients, the basal PRL levels were significantly higher than those of the other 59 normoprolactinemic women. No significant differences in gonadotropin concentrations were detected among the three groups. The unusual rise in PRL levels after LRH in these 13 patients can be interpreted as a paradoxical response of the pituitary to a specific stimulus, as seen in other clinical conditions. It is suggested that this phasic hyperprolactinemia might represent an intermediate phase between true normoprolactinemia and chronic hyperprolactinemia. 相似文献
20.
Injection of 100 micrograms 2-hydroxyestrone (2OHE1) at various times on the morning of proestrus into normal 4-day-cycling rats results in abolition of the preovulatory LH surge in a number of animals tested. The greatest response was observed when the administration of 2OHE1 coincided with endogenous estradiol (E2) levels that were close to but not at their maximal proestrous levels. The catechol estrogen failed to abolish the LH surge if given much earlier or after the E2 maximum had already been reached. The effectiveness of 2OHE1 inhibition of the LH surge was greatly increased by the administration of 1 microgram E2 1 h before the catechol estrogen. 2OHE1 did not interfere with LH secretion in response to LHRH administration, indicating that the inhibitory action of the catechol estrogen is exercised at the hypothalamic level. In contrast to its inhibition of the positive feedback, 2OHE1 administered either before or after the injection of E2 to ovariectomized rats had no effect on the negative feedback of the hormone on pituitary LH secretion. The narrow and specific "time window" on proestrus when an injection of 2OHE1 results in the abolition of the preovulatory LH surge and its relation to the endogenous E2 preovulatory secretion suggest that the catechol estrogen interferes with a brief neuronal triggering event obligatory for LHRH release. The evidence also indicates that this action does not involve conventional competition for the E2 receptor. 相似文献