Dynamics of messenger RNAs encoding inhibin/activin subunits and follistatin in the ovary during the rat estrous cycle

Quantitative changes in ovarian inhibin/activin subunit and follistatin mRNAs during the rat estrous cycle were examined by ribonuclease protection assay using digoxygenin-labeled RNA probes. Levels of ovarian inhibin alpha subunit mRNA remained low throughout estrus, metestrus, and diestrus; abruptly increased on the morning of proestrus; then rapidly decreased when the primary gonadotropin surge occurred. A similar changing pattern was observed in inhibin/activin beta(A) subunit mRNA. On the other hand, inhibin/activin beta(B) subunit mRNA showed a different changing pattern. Levels of beta(B) subunit mRNA remained constant during metestrus and diestrus, abruptly decreased on the afternoon of proestrus, then quickly recovered from the nadir by 1100 h on estrus. Throughout the rat estrous cycle, especially during the periovulatory period, alpha subunit mRNA levels were considerably higher than beta(A) and beta(B) subunit mRNA levels. In addition, changes in plasma concentrations of inhibin A and inhibin B were very similar to that in ovarian beta(A) and beta(B) subunit mRNA levels, respectively, with several-hour delays. These results suggest that levels of beta subunit mRNAs restrict secretion of dimeric inhibins. Levels of follistatin mRNA remained low from the midnight of metestrus to the midnight of diestrus, then increased until initiation of the primary gonadotropin surge. Thereafter, follistatin mRNA decreased, reached the nadir at 0200 h on estrus, then increased abruptly at 1100 h on estrus. Afterward, follistatin mRNA levels remained high until the morning of metestrus. The changing pattern of ovarian follistatin mRNA was similar to, and preceded, the changes in plasma concentrations of progesterone, suggesting that ovarian follistatin may modulate progesterone secretion during the rat estrous cycle.     

Does corpus luteum function autonomously during estrous cycle in the rat? A possible involvement of LH and prolactin

This study examined the of LH and prolactin in the control of corpus luteum function during 4-day cycles in the rat. Bromocriptine (BRC) treatment was performed on proestrus or/and estrus morning that means before or after the preovulatory release of LH. This caused complete blood prolactin depression from the time of injection until diestrus 1 afternoon. This decrease in blood prolactin concentration was associated with a rise in the tonic level of LH secretion in those females which received BRC as soon as on proestrus. We first observed that injection on the morning of proestrus of doses of BRC capable of blunting prolactin secretion on proestrus afternoon did not significantly impair the preovulatory release of LH and did not prevent ovulation occurring during the following night. The life span of the corpora lutea edified from ovarian follicles rupturing before or under BRC administration did not exceed that of those formed under physiological circumstances since 4-day cycles culminating in ovulation constantly took place in all the treated animals whatever the time of BRC injection. To determine the pattern of luteal activity in the absence of prolactin secretion, we measured blood progesterone concentration from estrus until late diestrus in female rats injected with BRC on proestrus and/or estrus at 1100 h. The initiation of the function of corpus luteum on estrus and the achievement of its full activity on diestrus 1 did not appear to be affected by BRC. By contrast the level of blood progesterone declined more rapidly on the morning of diestrus 2 in BRC-treated than in control females. The capacity for autonomous progesterone secretion by corpus luteum of the cycle was discussed in the light of previous and present observations.     

Oxytocin secretion induced by osmotic stimulation in rats during the estrous cycle and after ovariectomy and hormone replacement therapy

Hyperosmolality is a potent stimulus for the secretion of oxytocin. Oxytocinergic neurons are modulated by estrogen and oxytocin secretion in rats varies according to the phase of the estrous cycle, with higher activity during proestrus. We investigated the oxytocin secretion induced by an osmotic stimulus (0.5 M NaCl) in female rats. Plasma oxytocin and the oxytocin contents in the neurohypophysis and the paraventricular and supraoptic nuclei were determined during the morning (8-9 h) and afternoon (17-18 h) of the estrous cycle and after ovariectomy followed or not by hormone replacement. Plasma oxytocin peaked in control animals during proestrus. Oxytocin content decreased in the paraventricular and supraoptic nuclei during proestrus and estrus compared to diestrus and increased in the neurohypophysis during proestrus morning. No significant difference was observed in the oxytocin content of the neurohypophysis, nuclei or plasma between ovariectomized animals and ovariectomized animals treated with estrogen or estrogen plus progesterone. Therefore, any ovarian factor other than estrogen or progesterone seems to play a direct or indirect role in the increase in oxytocin secretion. The osmotic stimulus caused an increase in plasma oxytocin throughout the estrous cycle. A reduction in oxytocin content during diestrus and an increase during proestrus were observed in the paraventricular nuclei. In ovariectomized animals, the treatment with estrogen potentiated the response of oxytocin to the osmotic stimulus, with the response being even stronger in the case of estrogen plus progesterone. In conclusion, the ovarian steroids estrogen plus progesterone could modulate the osmoreceptor mechanisms related to oxytocin secretion.     

Control of follicular development and luteal function in the mare: effects of a GnRH antagonist

Control of the equine estrous cycle was studied by suppressing gonadotropin secretion by administration of a GnRH antagonist to cyclic pony mares. Four mares received vehicle (control cycle) or a GnRH antagonist, Antarelix (100 microg/kg) on Day 8 of diestrus, and blood samples were collected at 15-min intervals from 0 to 16 h, 24 to 36 h, and daily until the next ovulation. Ovarian activity was monitored by transrectal ultrasonography, and measurement of plasma concentrations of progesterone and estradiol. Antagonist treatment eliminated large diestrous pulses of LH. Progesterone concentrations had fallen significantly in all mares by the day after treatment and, in three of the four mares, remained low until luteolysis. However timing of luteolysis (ie., progesterone concentrations <1 ng/mL) was not affected by antagonist treatment. The preovulatory surges of estradiol and LH were significantly delayed in the treatment cycle, as was the appearance of a preovulatory follicle >30 mm. Cycle length was significantly longer during the treatment than the control cycle. These results show that treatment of diestrous mares with a GnRH antagonist attenuated progesterone secretion, indicating a role for LH in control of CL function in the mare, and delayed ovulation presumably because of lack of gonadotropic support.     

Uterine and ovarian blood flow during the estrous cycle in mares

Uterine and ovarian blood flow was investigated in four mares during two consecutive estrous cycles using transrectal color Doppler sonography. The uterine and ovarian arteries of both sides were scanned to obtain waves of blood flow velocity. The pulsatility index (PI) reflected blood flow. There were significant time trends in PI values of all uterine and ovarian blood vessels during the estrous cycle (P < 0.05). PI values did not differ between the uterine arteries ipsi- and contralateral to the corpus luteum or the ovulatory follicle. PI values of the uterine arteries showed a wave shaped profile throughout the estrous cycle. The highest PI values occurred on Days 0 and 1 (Day 0 = ovulation) and around Day 11, and the lowest PI values were measured around Days 5 and -2 of the estrous cycle. During diestrus (Days 0-15) PI values of the ovarian artery ipsilateral to the corpus luteum were significantly lower than PI values of the contralateral ovarian artery (P < 0.0001). No differences (P > 0.05) in resistance to ovarian blood flow occurred between sides during estrus (Days -6 to -1). In this cycle stage PI values decreased in both ovarian vessels (P < 0.05). During diestrus, high PI values of the ovarian artery ipsilateral to the corpus luteum were measured between Days 0 and 2, followed by a decline until Day 6 (P < 0.05). From this time on, the resistance to blood flow increased continuously until Day 15 (P < 0.05). The cyclic blood flow pattern in the contralateral ovarian artery was similar to that in the uterine arteries (r = 0.68; P < 0.0001). No correlations occurred between the diameter of the corpus luteum and the PI values of the ipsilateral ovarian artery (P > 0.05) during diestrus. During estrus, there was a negative relationship between growth of the diameter of the ovulatory follicle and changes in PI values of the dominant ovarian artery (r = -0.41; P < 0.05). PI values of the uterine arteries and of the ovarian artery ipsilateral to the ovulatory follicle were negatively related to estrogen (E) levels in plasma during estrus (uterine arteries: r = -0.21; P < 0.05; dominant ovarian artery: r = -0.35; P < 0.05). In diestrus, PI values of the dominant ovarian artery were negatively related to plasma progesterone levels (r = -0.38; P < 0.0001), but not the PI values of the uterine arteries (P > 0.05). The findings of this study show that there are characteristic changes in blood supply of the uterus and the ovaries throughout the equine estrous cycle. There are negative correlations between resistance to blood flow in the uterine and ovarian arteries and the plasma estrogen levels during estrus. In diestrus, there is a negative relationship between the resistance to ovarian blood flow and the progesterone levels.     

Ovarian atrial natriuretic peptide during the rat estrous cycle.

The changes in ovarian levels of immunoreactive atrial natriuretic peptide (irANP) and arginine vasopressin (irAVP) were observed during the estrous cycle of rat. We also demonstrated the synthesis of ovarian ANP. In adult 4-day cycling rats, ovarian level of irANP was found to be the highest on proestrus and was to be the lowest on diestrus. Ovarian irANP level inversely correlated with ovarian level of irAVP. On reverse-phase HPLC, two distinct peaks of ovarian irANP, high and low molecular weight forms, existed in the each stage of the estrous cycle. However, no significant changes in plasma and atrial concentrations of ANP were observed during the cycle. The rat ovary contained mRNA coding for ANP. These data showing the synchronized cyclic change of ovarian irANP and irAVP with the estrous cycle suggest that the ovary locally synthesizes ANP and ovarian ANP may play regulatory roles on the follicular fluid dynamics.     

Twenty-four-hour secretory patterns of cortisol,progesterone and estradiol in heifers during the follicular and luteal phases of the ovarian cycle

Daily variations of plasma cortisol, progesterone and estradiol concentrations were measured by radioimmunoassay in six different normally cycling heifers during estrus (day 1 of the cycle) and diestrus (days 12–15 of the cycle). Each animal was fitted with an indwelling jugular catheter, and blood was withdrawn at 30-min intervals over a 24-h period. Statistical evaluation of the hormonal profiles using time series analysis revealed that all three steroids are secreted episodically with secretory episodes varying in number, magnitude and timing among different heifers. After dividing the 24-h into three 8-h time periods (I, 09.00–17.00 h; II. 17.00–01.00h; III, 01.00–09.00 h) a prominent circadian rhythm was found for cortisol during estrus and diestrus. Diurnal periodicity similar to that of cortisol was noticed for plasma progesterone during estrus but not diestrus when a functional corpus luteum was present. Estradiol secretion during the follicular and luteal phase of the estrous cycle was characterized by intermittent sustained elevations lasting about 9–15 h and marked by a graded rise and fall of hormone levels unrelated to photoperiod.From our results obtained in cycling heifers we conclude the following: (1) Plasma cortisol exhibits a distinct circadian rhythm during estrus and diestrus which is highly correlated with the light–dark cycle. (2) Plasma progesterone during estrus demonstrates a diurnal pattern which is absent in diestrous heifers bearing a corpus luteum. (3) Plasma estradiol lacks circadian rhythmicity but shows a distinct pattern different from that of progesterone, indicating that both steroids are secreted independently and not controlled by a circadian pacemaker.     

Uterine motility in the cow during the estrous cycle. I. Spontaneous activity

This study describes a method for measuring intrauterine pressure (IUP) changes and uterine motility in cows. Spontaneous uterine motility was recorded during the estrous cycle in stanchioned, nonlactating dairy cows using a pair of miniature pressure transducers mounted 15 cm apart at the distal end of a dacron catheter placed in one uterine horn via the cervix. Clinical examination of ovarian status and determination of the peripheral plasma levels of estradiol-17beta and progesterone were used to determine the stages of the cycle. The pressure sensors recorded variations in muscular resting tension (tone) and the occurrence, spatial distribution, and force of the uterine contractions. Both tone and uterine activity varied significantly during the cycle. They were minimal during diestrus, increased during proestrus, reached maximal values at estrus, and then decreased. The highest synchronized motor activity with presence of peristaltic-antiperistaltic movements occurred during estrus. The prevailing direction of the uterine contractions during late estrus (immediate preovulatory period) was cervico-tubal.     

Changes in plasma progesterone, estradiol, follicle-stimulating hormone and luteinizing hormone during diestrus and ovulation in rats with 5-day estrous cycles: effect of antibody against progesterone

Progesterone secretion remained significantly higher during diestrus in the 5-day cyclic rat than in the 4-day cyclic animal. Injection of a sufficient amount of antiprogesterone serum (APS) at 2300 h on metestrus in a 5-day cycle advances ovulation and completion of the cycle by 1 day in the majority of animals (75 and 80%, respectively). Progesterone (250 micrograms) administered with APS eliminated the effect of the antiserum. Within 2 h after administration of APS, levels of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) elevated significantly, while a significant elevation of plasma estradiol above the control value followed as late as 36 h after the treatment. None of the 5-day cyclic rats treated with APS showed ovulatory increases of FSH and LH at 1700 h on the second day of diestrus, although 3 of the 4 animals receiving the same treatment ovulated by 1100 h on the following day. The onset of ovulatory release of gonadotropins might have been delayed for several hours in these animals. These results indicate that recurrence of the 5-day cycle is due to an elevated progesterone secretion on the morning of diestrus, and suggest that a prolongation of luteal progesterone secretion in an estrous cycle suppresses gonadotropin secretion. Rather than directly blocking the estrogen triggering of ovulatory LH surge, the prolonged secretion of luteal progesterone may delay the estrogen secretion itself, which decreases the threshold of the neural and/or hypophyseal structures for ovulatory LH release.     

The effects of indomethacin on plasma LH levels in female and male deermice (Peromyscus maniculatus)

The purpose of this investigation was to determine (1) the approximate time of the preovulatory LH rise in cyclic deermice, (2) the effect of indomethacin administration on plasma LH levels during the expected preovulatory LH rise, and (3) the effect of indomethacin administration on plasma LH levels in castrated male deermice. The data indicate that the preovulatory LH rise occurred at about 2200 h on proestrus and that indomethacin pretreatment significantly reduced plasma LH levels during that time. In addition, indomethacin significantly reduced plasma LH levels in castrated male deermice. We conclude that plasma LH levels remain low throughout the estrous cycle with the exception of the preovulatory “surge”, that plasma LH levels in deermice are comparable to those reported for the rat, and that indomethacin pretreatment reduced plasma LH levels during periods when they were expected to be elevated (in castrated males and during the expected preovulatory LH rise in female deermice). The data are consistent with the hypothesis that the effect of indomethacin on plasma LH levels is due to an inhibitory effect on hypothalamic PG biosynthesis.     

The effects of indomethacin on plasma LH levels in female and male deermice ( )

The purpose of this investigation was to determine (1) the approximate time of the preovulatory LH rise in cyclic deermice, (2) the effect of indomethacin administration on plasma LH levels during the expected preovulatory LH rise, and (3) the effect of indomethacin administration on plasma LH levels in castrated male deermice. The data indicate that the preovulatory LH rise occurred at about 2200 h on proestrus and that indomethacin pretreatment significantly reduced plasma LH levels during that time. In addition, indomethacin significantly reduced plasma LH levels in castrated male deermice. We conclude that plasma LH levels remain low throughout the estrous cycle with the exception of the preovulatory “surge”, that plasma LH levels in deermice are comparable to those reported for the rat, and that indomethacin pretreatment reduced plasma LH levels during periods when they were expected to be elevated (in castrated males and during the expected preovulatory LH rise in female deermice). The data are consistent with the hypothesis that the effect of indomethacin on plasma LH levels is due to an inhibitory effect on hypothalamic PG biosynthesis.     

Control of Ovarian Function in Domestic Animals

Plasma hormone levels during the estrous cycle of the cow, ewe,and sow have been measured, and the patterns of secretion ofestrogens, progesterone, and luteinizing hormone during thecycle have been related to ovarian changes and other informationconcerning the cycle for each species. Peripheral plasma progesteroneand LH levels are generally inversely related during the cyclein each species, and it seems clear that progesterone exertsa negative feedback on LH secretion in all three species, atleast insofar as the cyclic release of preovulatory amountsof LH is concerned. Peak plasma progesterone levels are highestin the sow, lowest in the ewe, and intermediate in the cow.Plasma LH levels at estrus are highest in the ewe, lowest inthe sow, and intermediate in the cow. Sharp peaks in plasmaLH occur at the onset of estrus in the cow, and a few hoursafter the onset of estrus in the ewe and sow; these peaks areof about 6–8 hr duration. LH exerts a luteotrophic actionon the corpora lutea of all three species, and verylow levelsof LH secretion appear capable of maintaining the corpus luteumin the ewe and cow. There is no good evidence that prolactinis luteotrophic in any of these species. Three peaks of plasmaestrogen levels are seen in the ewe and the cow and these appearrelated to periods of accelerated follicle growth. One peakoccurs early in the cycle and before plasma progesterone levelsrise appreciably and another occurs during the luteal phasejust prior to corpus luteum regression. The third peak occursafter plasma progesterone levels decline and is associated withgrowth of the ovulating follicle. The luteal phase estrogenpeak has not been found in the sow. The rapid rise in bloodestrogens after the corpus luteum regresses facilitates thepreovulatorysurge of LH in all three species. Cyclical regressionof the corpus luteum in all three speciesappears to be underlocal control of the adjacent horn of the uterus. Exogenousestrogens are luteolytic in the cow and ewe, but luteotrophicin the sow. The ovaries of all three species contain very poorlydeveloped interstitial tissue probably because of the neailycomplete dedifftrentiation of the thecal cells during atresia.Thus, these animals lack an important source ofsteroid hormonespresent in the lodents and certain other species.     

Secretion of progesterone during long and short days of the estrous cycle in goats that are continuous breeders

This study was conducted 1) to determine if the secretion of progesterone, as an index of ovarian activity, during the estrous cycle of nonseasonal Shiba goats is affected by seasonal changes, and 2) to learn if the pulsatile secretion of ovarian progesterone can be estimated from samples obtained by cannulation into the caudal vena cava via the femoral vein. Progesterone concentrations in jugular venous plasma during the estrous cycle in spring (May) were similar to those in autumn (November). Plasma progesterone concentrations in the jugular vein and caudal vena cava monitored for 10 h on Day 12 of the estrous cycle in spring were similar to those in autumn. The mean concentration (21.9 to 28.9 ng/ml) and the pulse frequency (6.2 to 7.4 pulses/10 h) of plasma progesterone in the caudal vena cava during both seasons were 3.1- to 4.7-fold and 1.7- to 2.4-fold those in the jugular vein, respectively. The degree of change in the peak magnitude and the base-line concentration of progesterone were higher in the caudal vena cava than in the jugular vein. These results indicate that progesterone secretion during the estrous cycle in nonseasonal goats is not affected by seasonal changes, and suggest that the pulsatile secretion of ovarian progesterone can be evaluated better from samples obtained from the caudal vena cava, near where progesterone is released, than from those obtained from the jugular vein.     

Gonadotropin-releasing hormone binding sites in ovaries of normal cycling and persistent-estrus rats

The gonadotropin-releasing hormone (GnRH) binding capacity in ovaries and pituitaries of normal cycling rats at different stages of the estrous cycle and in ovaries of persistent-estrus rats was measured using radioligand-receptor assay (RRA). Persistent estrus was induced either by neonatal administration of testosterone propionate (1.25 mg s.c.) on the second day of life or by a hypothalamic suprachiasmatic frontal cut made with Halász' knife. All animals were killed during the critical period (1400-1600 h), and GnRH receptor was assayed. GnRH receptor levels in both ovaries and pituitaries changed during the estrous cycle. The total number of ovarian GnRH binding sites was significantly higher in proestrus than in diestrus 1, the stage in which the lowest level was found. When binding sites were expressed in fmol/mg ovary, the highest level was observed in diestrus 2; however, no changes were observed during the estrous cycle when GnRH binding sites were expressed as fmol/mg protein. Changes noted were very similar to those demonstrated in pituitary GnRH receptors in our present and previous experiments. Higher levels of pituitary binding sites were found in diestrus 2 and proestrus than in estrus and diestrus 1. The changes in the GnRH receptor levels were more striking in the pituitary than in the ovaries. It appears that the total number of ovarian GnRH binding sites was not altered in either of the two persistent-estrus groups, but that their concentration was significantly higher (expressed in fmol/mg ovary or fmol/mg protein) than on any day during the estrous cycle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Decreased luteinizing hormone-stimulated progesterone secretion by preovulatory follicles isolated from cyclic rats treated with the progesterone antagonist RU486.

Since administration of the antiprogesterone RU486 to cyclic female rats at metestrus and diestrus results in increased serum levels of LH, estradiol, and testosterone at proestrus, we investigated whether RU486 affects follicular steroidogenesis. Female rats with a 4-day estrous cycle, induced experimentally by a single injection of bromocriptine on the morning of estrus, were given RU486 (2 mg) twice daily (0900 and 1700 h) on metestrus and diestrus. At proestrus the preovulatory follicles were isolated and incubated for 4 h in the absence and presence of LH. In the absence of LH, accumulation of estradiol, testosterone, and progesterone in the medium was not different for RU486-treated rats and oil-treated controls. In contrast, LH-stimulated estradiol, testosterone, and progesterone secretions were significantly lower in RU486-treated rats compared with controls. Addition of pregnenolone to the incubation medium resulted in a significantly lower increase of progesterone in follicles from RU486-treated rats compared with those from oil-treated controls. This suggests that 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity is decreased by administration of RU486 in vivo. Aromatase and 17 alpha-hydroxylase/C17-20 lyase activities were not affected: addition of substrate (androstenedione and progesterone respectively) did not affect differently the amount of product formed (estradiol and testosterone) in RU486- and oil-treated rats. However, LH-stimulated pregnenolone secretion was lower in follicles from RU486-treated rats compared with follicles from oil-treated controls, suggesting that either cholesterol side-chain cleavage activity or LH responsiveness is decreased. At proestrus the preovulatory follicles from RU486- and oil-treated rats were not morphologically different.(ABSTRACT TRUNCATED AT 250 WORDS)     

A new progestin (Sa 45.249) for cycle control in pigs communication IV: Analysis of hormonal blood levels

Gilts were treated with 6 mg Sa 45.249/day for 12 to 14 days, starting at various stages of the estrous cycle. Blood levels of LH, estradiol 17β and progesterone were determined once or twice daily, before, during and after treatment. Treatment suppressed the cyclic preovulatory LH peak; estradiol levels started to rise during treatment and returned to base line levels with the commencement of standing heat. Formation, lifespan and regression of corpora lutea, as reflected by plasma progesterone levels, were not influenced by the progestin treatment.     

Intraovarian secretion of catecholamines, oxytocin, beta-endorphin, and gamma-amino-butyric-acid in freely moving rats: development of a push-pull tubing method

We have developed and validated a push-pull technique that allows focal perfusion of the ovary in unanesthetized freely moving rats. We have used this method to investigate the intraovarian secretion of catecholamines (dopamine, norepinephrine, epinephrine), oxytocin, beta-endorphin and gamma-amino-butyric acid (GABA) during the estrous cycle. Cycling animals were implanted with ovarian push-pull catheters and jugular vein catheters under ether anaesthesia on proestrus, estrus and diestrous Day 2. This procedure did not disrupt normal preovulatory release of prolactin and luteinizing hormone (LH). Thus, perfusion of the ovary and simultaneous monitoring of hormone levels in systemic blood in freely moving rats allow correlation of the temporal relationship of ovarian events with cyclic gonadotropin secretion. The results clearly indicate that a rise in ovarian norepinephrine occurs concomitant with the preovulatory surge in prolactin and LH. Ovarian beta-endorphin concentrations exhibit cyclic changes, whereas GABA release rates remain stable throughout the cycle. Oxytocin is secreted by ovarian tissue, and the secretion rate appears to be inversely related to prolactin. In view of the proposed involvement of ovarian nerves and particularly catecholamines in the process of follicular maturation and ovulation, our findings suggest a preovulatory activation of ovarian noradrenergic sympathetic neurons.     

Effects of thymulin and GnRH on the release of gonadotropins by in vitro pituitary cells obtained from rats in each day of estrous cycle

The effects of thymulin and GnRH on FSH and LH release were studied in suspension cultures of anterior pituitary cells from female adult rats sacrificed on each day of the estrous cycle. The spontaneous release of gonadotropins by pituitaries, as well as their response to GnRH or thymulin addition, fluctuated during the estrous cycle. Adding thymulin to pituitary cells from rats in diestrus 1 increased the concentration of FSH; while in cells from rats in estrus, FSH level decreased. Thymulin had a stimulatory effect on the basal concentration of LH during most days of the estrous cycle. Adding GnRH increased FSH release in cells from rats in diestrus 1, diestrus 2, or proestrus, and resulted in higher LH levels in cells obtained from rats in all days of the estrous cycle. Compared to the GnRH treatment, the simultaneous addition of thymulin and GnRH to cells from rats in diestrus 1, diestrus 2, or proestrus resulted in lower FSH concentrations. Similar results were observed in the LH release by cells from rats in diestrus 1, while in cells from rats in proestrus or estrus, LH concentrations increased. A directly proportional relation between progesterone serum levels and the effects of thymulin on FSH release was observed. These data suggest that thymulin plays a dual role in the release of gonadotropins, and that its effects depend on the hormonal status of the donor's pituitary.     

Endocrine alterations that underlie endotoxin-induced disruption of the follicular phase in ewes

Two experiments were conducted to investigate endocrine mechanisms by which the immune/inflammatory stimulus endotoxin disrupts the follicular phase of the estrous cycle of the ewe. In both studies, endotoxin was infused i.v. (300 ng/kg per hour) for 26 h beginning 12 h after withdrawal of progesterone to initiate the follicular phase. Experiment 1 sought to pinpoint which endocrine step or steps in the preovulatory sequence are compromised by endotoxin. In sham-infused controls, estradiol rose progressively from the time of progesterone withdrawal until the LH/FSH surges and estrous behavior, which began approximately 48 h after progesterone withdrawal. Endotoxin interrupted the preovulatory estradiol rise and delayed or blocked the LH/FSH surges and estrus. Experiment 2 tested the hypothesis that endotoxin suppresses the high-frequency LH pulses necessary to stimulate the preovulatory estradiol rise. All 6 controls exhibited high-frequency LH pulses typically associated with the preovulatory estradiol rise. As in the first experiment, endotoxin interrupted the estradiol rise and delayed or blocked the LH/FSH surges and estrus. LH pulse patterns, however, differed among the six endotoxin-treated ewes. Three showed markedly disrupted LH pulses compared to those of controls. The three remaining experimental ewes expressed LH pulses similar to those of controls; yet the estradiol rise and preovulatory LH surge were still disrupted. Our results demonstrate that endotoxin invariably interrupts the preovulatory estradiol rise and delays or blocks the subsequent LH and FSH surges in the ewe. Mechanistically, endotoxin can interfere with the preovulatory sequence of endocrine events via suppression of LH pulsatility, although other processes such as ovarian responsiveness to gonadotropin stimulation appear to be disrupted as well.