Biomedical subjects

M Tébar

Publications and source records attributed to M Tébar.

At least 19 recordsLinked to original sources

PubMed2000

Regulation of inhibin/activin subunits and follistatin mRNA expression in the rat pituitary at early estrus.

In the rat pituitary, activin stimulates whereas inhibin prevents FSH synthesis and secretion. Besides, the activin binding protein follistatin neutralizes the action of activin. The control of the FSH secondary surge at early estrus is not completely understood. To investigate the regulation of the inhibin/activin alpha-, betaA- and betaB-subunits and follistatin mRNA expression in the pituitary during the time of the FSH secondary surge, cyclic rats treated with LHRH antagonist (ANT) and ovine LH (oLH), progesterone (P), the anti-steroid RU486, adrenalectomy (ADX) or ADX plus corticosterone (B), were killed at early estrus. The serum concentrations of FSH were measured and the mRNA levels of the above mentioned transcripts were analysed and quantitated by using RNase protection assays. ANT abolished the FSH secondary surge and increased mRNA for alpha- and betaA-subunits and follistatin, but reduced that for betaB-subunit. Both oLH and P reversed these effects. RU486 blocked the effect of oLH on FSH levels and prevented the reduction in the mRNA for follistatin. ADX in ANT+oLH-treated rats reduced the serum FSH concentrations, enhanced mRNA for betaA- and betaB-subunits and, similar to RU486, blocked the drop in follistatin mRNA. Finally, replacement of B in ADX animals reversed these effects. These results demonstrate that, in the cyclic rat, the preovulatory secretion of LH and the surges of P and B on proestrus regulate the synthesis of inhibin/activin subunits and follistatin mRNA in the rat pituitary at early estrus, probably by reducing inhibin and follistatin and increasing activin. Moreover, these effects of LH, P and B at the pituitary level, together with the decrease in the amount of inhibin coming from the ovary, might be responsible for the occurrence of the FSH secondary surge.

Activins↗

PubMed2000

Comparison of the effects of antiprogestins RU38486, ZK98299 and ORG31710 on periovulatory hypophysial, ovarian and adrenal hormone secretion in the rat.

The antiprogestin (AP) RU38486 (RU) blocks progesterone (P) and glucocorticoid (G) actions. Administration of 4 mg RU on proestrous morning to cyclic rats dissociates LH and FSH secretion on proestrous afternoon, early estrus and on estrous afternoon. In order to ascertain which action blocked by RU is predominant in the control of periovulatory LH and FSH secretion, a study was made on the effects of: a) 1 or 4 mg of ZK98299 (ZK) (type I P antagonist; Schering), b) 2 or 8 mg of Org31710 (OR) (type II P antagonist lacking anti-G actions; Organon) or c) 1 or 4 mg of RU (type II P antagonist; Exelgyn) to 4-day cyclic rats on proestrous morning on serum concentrations of LH, FSH, inhibin-alpha (I), estradiol-17beta (E), progesterone (P) and corticosterone (B) at 18:30 h on proestrus and at 02:00 and 18:30 h on estrus. Controls, receiving 0.2 ml oil, had elevated serum concentrations of all six hormones on proestrous afternoon; at early estrus, only serum concentrations of FSH and P remained elevated, and, on estrous afternoon, all hormones but I and B, that peaked again, had reached their lowest serum levels. All AP treatments except 1 mg ZK had the same effects. On proestrous afternoon serum LH concentrations were reduced and serum FSH concentrations were suppressed whereas serum levels of I, E, P and B were unaffected. At early estrus, basal serum concentrations of LH and E increased while FSH secretion was abolished. Serum levels of I, P and B did not differ from controls. AP treatments increased basal LH concentration, hyperstimulated FSH secretion and reduced serum I concentration on the afternoon of estrus. E, P and B serum levels did not differ from controls at this stage. Treatment with 1 mg ZK was less effective in reducing serum FSH on proestrous afternoon and at early estrus, and had no effect on serum concentrations of any hormone on estrous afternoon. These results indicate that blockade of P receptor activation by P is, predominantly, the mechanism of AP action on periovulatory gonadotropin secretion in rats.

Adrenal Glands↗

PubMed1999

Mechanism of the stimulatory action of antisteroid RU486 on follicle-stimulating hormone secretion in the cyclic Rat.

These experiments explored the mechanism underlying FSH hypersecretion on estrous afternoon in rats injected with RU486 (RU) on proestrus. Four-day cyclic rats were injected with RU at 12:00 h on proestrus (1 or 4 mg/0.2 ml oil; s.c.), and its effects on LH and FSH secretion at 18:30 h on estrus were compared with those of antiprogestagens ZK299 (ZK) (1 or 4 mg/0.2 ml oil; s.c.) and Org31806 (OR) (2 or 8 mg/0.2 ml oil; s.c.). Additionally, rats treated with RU or nembutal (PB) (60 mg/kg; i.p. at 13:00 h on proestrus) were injected with an LHRH antagonist (LHRHa) at 10:00 h on estrus (1 mg/0.2 ml saline; s.c.) or progesterone (P) (7.7, 15.5 or 30.9 mg/0.2 ml oil; s.c.) on proestrus at 10:00 h in RU-injected rats and at 14:00 h in PB-injected rats. Animals were killed by decapitation at 18:30 h on estrus and serum LH and FSH concentrations were determined. Rats treated with 1 or 4 mg of RU or Org or 4 mg of ZK recorded increased serum FSH on estrous afternoon, while 1 mg ZK had no effect. PB increased mainly serum LH levels and, to a lesser extent, FSH levels. P decreased serum FSH concentrations in both RU- and PB-injected rats. LHRHa reversed the effects of PB on FSH secretions, but reduced FSH hypersecretion induced by RU only. These results are interpreted to mean that, in the absence of proestrous afternoon P-inhibitory action of the neural stimulus controlling LHRH release, FSH secretion on estrous afternoon involves two components: one is LHRH dependent while, in contrast to LH secretion, the other is LHRH independent, and only expressed in a low estrogen background.

Animals↗

PubMed1999

The antiprogestin RU486 dissociates LH and FSH secretion in male rats: evidence for direct action at the pituitary level.

Administration of 4 mg of the antisteroid RU486 over 8 consecutive days to adult male rats dissociated in vivo and in vitro gonadotrophin secretion, increasing FSH and decreasing LH secretion. In subsequent experiments we evaluated the involvement of testicular or adrenal secretory products, as well as hypothalamic LHRH, in the effects of 4 consecutive days of RU486 treatment on the secretion of gonadotrophins. The first day of RU486 injection was designated day 1, subsequent days being numbered consecutively. Groups of rats injected with oil (0.2 ml) or RU486 (4 mg) were: (i) injected s.c. from day 1 to day 4 with the antiandrogen flutamide (10 mg/kg); (ii) bilateral orchidectomized (ORCH) on day 1; and (iii) bilateral adrenalectomized (ADX) on day 1. Controls were given flutamide vehicle or were sham operated. To ascertain whether the secretion of LHRH is involved in the effects of RU486 on gonadotrophin secretion, we measured the LHRH secretion into the pituitary stalk blood vessels at 1100 h on day 5 in oil- or RU486-treated rats. Additional oil- and RU486-treated rats were injected i.p. with 100 ng LHRH at 1000 h on day 5, or s.c. with 1 mg LHRH antagonist (LHRH-ANT) at 1000 h on days 2 and 4. Controls were given saline. All animals were decapitated at 1100 h on day 5, trunk blood collected and serum stored frozen until FSH, LH and testosterone assays.%While ADX had no effect on FSH and LH secretion in either oil- or RU486-treated rats, the removal of androgen negative feedback with flutamide treatment or by ORCH substantially increased serum levels of FSH and LH in both oil- and RU486-treated rats, and thus annulled the effects of RU486. No differences in pituitary stalk plasma LHRH concentrations were found between oil- and RU486-treated rats. Injection of LHRH increased serum FSH and LH concentrations in oil-treated rats but only, and to a lesser extent, LH concentrations in RU486-treated rats. Treatment with LHRH-ANT decreased serum concentrations of FSH and LH in both oil- and RU486-treated rats. These results suggest that RU486 inhibited LHRH-stimulated LH secretion at the pituitary level, and that FSH secretion increased in response to a reduction in the negative feedback of androgen.

Adrenalectomy↗

PubMed1998

Involvement of estrogen and follicle-stimulating hormone on basal and luteinizing hormone (LH)-releasing hormone-stimulated LH secretion in RU-486-induced 3-day estrous cycle in the rat.

Administration of 4 mg of the antiprogestogen RU-486 on proestrus (Day 1) to 4-day-cyclic rats advances the pituitary desensitization to negative estrogen feedback and enhances pituitary responsiveness to LHRH. These effects of RU-486 lead to a 1-day estrous cycle shortening. Moreover, administration of RU-486 in this study increased serum estradiol-17beta and decreased FSH concentrations during diestrus (experiment 1). The aim of the study was to examine the contribution of the excess of estrogen and the deficiency of FSH during diestrus to the 1-day estrous cycle-shortening effect of RU-486 when injected on Day 1 in 4-day-cyclic rats. The aim of the second and third experiments was to evaluate the effects of 3 mg/0.2 ml oil of the antiestrogen LY117018-HCl (LY) at 1800 h on Days 2 and 3, or 10 IU/0.2 ml saline of a recombinant human FSH (rhFSH) at 1700 h on Day 3 and at 0900 h on Day 4, with or without 100 ng/0.5 ml saline of LHRH at 1200 h on Day 4, on uterine weight and serum concentrations of LH and estradiol-17beta at 1300 h on Day 4 in rats given oil or RU-486 on Day 1 or 2. The aim of the fourth experiment was to evaluate the effect of combined LY and rhFSH treatments on uterine weight and serum levels of LH and estradiol-17beta in rats injected with RU-486 on Day 1. Administration of RU-486 on Day 1 significantly increased serum estradiol-17beta on Days 3 and 4, whereas administration on Day 2 slightly increased serum estradiol-17beta on Day 4 only. Injection of RU-486 on either Day 1 or 2 decreased FSH serum concentrations on Days 3 and 4 to a similar extent. Treatment with LY reduced both basal and LHRH-stimulated LH secretion only in rats injected with RU-486 on Day 1, while rhFSH treatment attenuated basal and stimulated LH secretion regardless of treatment. Treatment with LY and rhFSH combined completely reversed the effects of RU-486 on Day 1 on LH serum concentrations. These data suggest that both the increased estradiol-17beta and the decreased FSH serum concentrations during diestrus in rats given RU-486 on proestrus are involved in the changes of pituitary function leading to a 1-day estrous cycle shortening.

Animals↗

PubMed1998

Effect of RU486 injected on proestrous morning on LHRH, LH and 17beta-estradiol secretion during the estrous cycle in rat.

The antiprogesterone RU486 injected on proestrus to cyclic rats advances the preovulatory surge of LH, resulting in a 3-day estrous cycle. To ascertain whether proestrous progesterone secretion regulates ovulation by synchronizing the functions of the ovary, the pituitary and the hypothalamus, in this study the effects of RU486 (4 mg/0.2 ml oil/s.c.) at 09:00 h on proestrus (day 1), on LHRH secretion into the pituitary stalk blood vessels and on peripheral plasma concentrations of LH and 17beta-estradiol at 10:00 h and at 18:00 h on each day of the estrous cycle, have been investigated. Control rats present the expected surges of LHRH and LH at 18:00 h on day 1 and a second increase in LHRH but no LH secretion was found in the afternoon of day 2. RU486 decreases both LHRH and LH surges in the afternoon of day 1, while it increases plasma concentrations of LHRH and LH in the morning of day 2. During the rest of the estrous cycle RU486-injected rats show high basal secretion of LH in comparison to controls, and at 18:00 h of day 4 advanced preovulatory surges of both LHRH and LH are present in RU486-injected rats. In relation to 17beta-estradiol concentrations, RU486 injection increases those on day 3 and induces an advanced preovulatory surge of 17beta-estradiol in the morning of day 4. These results show that, in the 4-day cyclic rat, the 24 hours-shortening of the estrous cycle induced by the antiprogesterone RU486 is due to the enhanced secretion of estrogen during the days of metestrus and diestrus, which stimulates the release of a surge of LHRH in the afternoon of diestrus and this, in turn, induces the advanced preovulatory surge of LH.

Animals↗

PubMed1997

Serum levels of GH, IGF-I, LH and ovarian steroids in cyclic and RU486-treated rats.

Rats lacking progesterone action due to RU486 treatment have been reported to show numerous endocrine and morphological similarities with respect to human polycystic ovary syndrome (PCO). Nevertheless, abnormalities on insulin or insulin-like growth factor I (IGF-I) production, a frequent finding in the polycystic disease, have not been studied in such rats yet. The aim of these experiments was to evaluate the serum concentrations of IGF-I in rats treated with 4 mg of the antiprogestagen RU486 over 4 or 8 consecutive days starting on estrus (day 1) and decapitated on the morning of day 5 and 9. Serum levels of growth hormone (GH), luteinizing hormone (LH), testosterone (T) and 17 beta estradiol (E2) were determined and correlated with those of IGF-I. Controls were rats injected with oil and killed in the morning of metestrus, diestrus, proestrus and estrus. Rats treated with RU486 had increased serum concentrations of IGF-I, LH, T and E2 with respect to control rats on estrus, while no differences were found in the serum concentrations of GH. Parallel estrous cycle related changes were observed in the serum concentrations of IGF-I, T and E2 with the highest values at proestrus. However, changes on serum concentrations of GH were not associated with those of IGF-I in control rats through the estrous cycle. The present results are consistent with the idea that beside on GH, serum concentrations of IGF-I in the rat depend also on LH or LH-dependent ovarian steroid production. Moreover, the results indicate that IGF-I production increased in RU486-treated rats, which may have a role in the ovarian abnormalities induced by RU486 treatment in the rat.

Animals↗

PubMed1997

Effects of progesterone on the secondary surge of follicle-stimulating hormone in the rat.

In the cyclic rat, the secondary surge of FSH on estrus appears to depend on the LH surge-induced fall in serum concentrations of inhibin. To investigate the involvement of progesterone in the regulation of the secondary surge of FSH, 4-day cyclic rats were treated on proestrus with an antagonist of LHRH (LHRHant) and with an ovulatory dose of ovine (o) LH, progesterone, the antiprogestin RU486, or the combination of RU486 and oLH. Serum concentrations of gonadotropins and inhibin at 1830 h on proestrus and at 0030 h on estrus were determined, and the expression of inhibin/activin subunit mRNAs in the ovary at 0030 h on estrus was analyzed by in situ hybridization. Rats receiving saline showed low expression of alpha-, beta(A)-, and beta(B)-subunit mRNAs in the ovary and low serum levels of inhibin in conjunction with the elevated serum concentrations of FSH on estrus. Administration of LHRHant blocked the decrease in the synthesis and secretion of inhibin and abolished the FSH secondary surge, whereas the injection of oLH prevented these effects. Exogenous progesterone, compared with LHRHant injection, increased alpha-, beta(A)-, and beta(B)-subunit mRNA hybridization intensity in the ovary and serum inhibin immunoreactivity, and also restored, in part, the surge of FSH on estrus. The antiprogestin RU486 did not modify the effect of oLH on either inhibin/ activin subunit mRNAs in the ovary or serum levels of inhibin, but blocked the FSH surge. These results indicate that, in the cyclic rat, 1) the secretion of progesterone on proestrous afternoon, induced by the LH surge, is not involved in the fall of ovarian inhibin synthesis and secretion; and 2) in combination with a drop in serum inhibin, a stimulatory action of progesterone on another factor, possibly pituitary activin, could be necessary to elicit a complete secondary surge of FSH.

Animals↗

PubMed1997

The steroid antagonist RU486 given at pro-oestrus induces hypersecretion of follicle-stimulating hormone from oestrus afternoon to early metoestrus in the rat.

Administration of the steroid antagonist RU486 to cyclic rats at pro-oestrus blunts the preovulatory surge of LH and suppresses the first and second surges of FSH. In addition, administration of oestradiol to RU486-treated rats reactivates the LH surge the following day. The present study explored the effects of RU486 (4 mg/0.2 ml oil), administered at 0800 h on the day of pro-oestrus, on serum FSH and LH concentrations through oestrus and early metoestrus. RU486 induced a hypersecretion of FSH, which started at 1400 h on the day of oestrus and was maintained until 0800 h on the day of metoestrus. Because the timing and magnitude of this secretion of FSH were similar to those of the periovulatory secretion of FSH during pro-oestrus and early oestrus in intact cyclic rats, we investigated the effects of: 1) LHRH antagonist (LHRHa) injected at either 0900 h or 2000 h on the day of oestrus, 2) oestradiol benzoate injected at 1600 h on the day of pro-oestrus and at 0900 h on the day of oestrus, 3) bovine follicular fluid (bFF) given either at 1100 h or at 2000 h on the day of oestrus, or 4) adrenalectomy (ADX) at 1100 h on the day of oestrus, on serum FSH and LH concentrations at 1800 h on the day of oestrus and at 0200 h on the day of metoestrus in rats injected with RU486 at pro-oestrus. The results showed that 1) both components (late oestrus and early metoestrus) of FSH hypersecretion in RU486-injected rats in pro-oestrus were inhibited by oestradiol benzoate and bFF, 2) the metoestrous component was not affected by LHRHa, whereas the oestrous component was partially reduced, and 3) ADX partially reduced serum FSH concentrations only on the day of metoestrus, possibly because, as the serum concentrations of corticosterone reflected, the antiglucocorticoid activity of 4 mg RU486 lasted only 24 h. The results support the hypothesis that blockade of progesterone actions at pro-oestrus results in the maintenance of the daily neural signal that activates the release of gonadotrophins. Whereas the expression of LH secretion requires high levels of oestradiol, FSH secretion is expressed against a background of low oestradiol levels. The results of this study also indicate that the release of FSH during oestrus and metoestrus in rats injected with RU486 at pro-oestrus is a consequence of the lack of ovarian negative feedback inhibition on the pituitary.

Adrenalectomy↗

PubMed1996

Antiprogestagen RU486 prevents the LH-dependent decrease in the serum concentrations of inhibin in the rat.

1. In the rat, the LH-dependent ovarian progesterone rise mediates several actions of the primary surge of LH on the ovary. This experiment was aimed at elucidating the effects of the antiprogestagen RU486 on the LH-dependent decrease in both the serum concentrations and the ovarian content of inhibin. 2. All rats in this experiment were treated with an antagonist of LHRH (1 mg/200 microliters saline at 0800 h in proestrus) to suppress the endogenous release of LH. One group of rats received 32 micrograms LH/250 microliters saline at 1200 h in proestrus. Other group was given 4 mg RU486/200 microliters oil at 0800 h in proestrus. The third group was injected with both RU486 and LH. Rats from the control group were injected with 250 microliters saline and 200 microliters oil. Animals were decapitated at 1700 h in proestrus and trunk blood and ovaries collected to determine the serum concentrations of LH, FSH, progesterone, 17 beta-estradiol and inhibin as well as the ovarian content of inhibin. 3. The ovulatory dose of LH in LHRHa-treated rats decreased both the serum concentrations and the ovarian content of inhibin and increased the serum concentrations of FSH. The administration of RU486 blocked the effect of LH on the serum concentrations of inhibin but not that on the ovarian content of inhibin. 4. Since the antiprogestagen RU486 blocked the effect of LH on the serum concentrations of inhibin, we conclude that ovarian progesterone, besides mediating the effects of the primary LH surge on the ovulatory process and luteinization, participates in the LH-dependent drop in the serum concentrations of inhibin in proestrous afternoon.

Animals↗

PubMed1996

Hypersecretion of follicle-stimulating hormone (FSH) on estrous afternoon in rats treated with RU486 in proestrus.

1. Intact or ovariectomized (OVX) cyclic rats injected or not with RU486 (4 mg/0.2 ml oil) from proestrus onwards were bled at 0800 and 1800 h on proestrus, estrus and metestrus. Additional RU486-treated rats were injected with: LHRH antagonist (LHRHa), estradiol benzoate (EB) or bovine follicular fluid (bFF) and sacrificed at 1800 h in estrous afternoon. LH and FSH serum levels were determined by RIA. 2. RU486-treated intact or OVX rats had decreased preovulatory surges of LH and FSH, abolished secondary secretion of FSH and hypersecretion of FSH in estrous afternoon. The latter was decreased by LHRHa and abolished by EB or bFF. In contrast, EB induced an hypersecretion of LH in RU486-treated rats at 1800 h in estrus. 3. It can be concluded that in the absence of the proestrous progesterone actions, the absence of the inhibitory effect of the ovary in estrus evoked a LHRH independent secretion of FSH.

Animals↗

PubMed1996

Ovary mediates the effects of RU486 given during proestrus on the diestrous secretion of luteinizing hormone in the rat.

The aim of these experiments was to study the action of proestrous afternoon follicular progesterone secretion on the preovulatory secretion of gonadotropins in the rat. Four-day-cycling rats were given 4 mg of the antiprogestagen RU486 in the morning of proestrus (Day 1), and its effects on the pituitary function during diestrus were compared with those of RU486 given in the morning of estrus (Day 2). The pituitary function was assessed by measuring basal secretion of LH and FSH as well as the pituitary response to either estradiol benzoate (EB) (3 mug/100 g BW at 1300 h on Day 3) or LHRH (100 ng/rat at 1200 h on Day 4). In all experiments, trunk blood was taken at 1300 h on Day 4 to measure serum gonadotropin concentrations. In rats receiving an injection of RU486 on estrus, the absence of only the diestrous progesterone actions increased basal serum concentrations of LH and decreased those of FSH, and as in vehicle-treated controls, EB inhibited and LHRH stimulated LH secretion. In contrast, the absence of both proestrous afternoon and diestrous progesterone actions (as characterized rats treated with RU486 on proestrus) antagonized the inhibitory effect of EB and sensitized the pituitary to LHRH. These effects of RU486 on proestrus are ovary-dependent and eliminated by ovariectomy on metestrus. The increased ovarian secretion of testosterone and estradiol-17 beta during diestrus does not mediate the effects of proestrus-administered RU486 on pituitary function: no differences were found in the serum concentrations of estradiol-17 beta in diestrus between the groups of rats treated with RU486, and administration of the antiandrogen flutamide (2 mg/rat at 0900 h on Days 2 and 3) did not reverse the effects of RU486 on proestrus. In conclusion, the results suggest that in the absence of proestrous afternoon progesterone action, the ovaries of the 4-day-cyclic rat keep the pituitary gland in a state of low sensitivity to the inhibitory effects of estradiol and high sensitivity to the stimulatory effects of LHRH. Moreover, the results suggest that the putative ovarian factors involved are factors other than progesterone, androgens, or estradiol-17 beta.

Androgen Antagonists↗

PubMed1996

Follicular and luteal progesterone synergize to maintain 5-day cyclicity in rats.

The length of the ovarian cycle in rat is determined by the duration of progesterone secretion from the corpora lutea (CL) during diestrus. The action of progesterone secretion from the preovulatory follicles on proestrus is also responsible for the cycle length in 4-day cyclic rats. To study whether follicular and luteal progesterone participate in the maintenance of 5-day cyclicity, the effects of the antiprogestagen RU486 (5 mg on proestrus or estrus) on estrous cycle length and on the serum concentrations of LH in 5-day cyclic rats and in 4-day cycle experimentally induced by the dopamine agonist CB154 (1 mg on estrus) were investigated. Furthermore, serum concentrations of progesterone on the day of ensuing ovulation were measured to see whether activation of the CL function after treatment with RU486 had occurred. Both 5-day and CB154-injected rats had a 3-day estrous cycle after RU486 on proestrus, while RU486 on estrus shortened by 1-day the estrous cycle length in 5-day but not in CB154-injected rats. Basal serum concentrations of LH increased and the LH surge decreased after RU486 treatment in both cycle types. Serum concentrations of progesterone rose only in 5-day rats injected with RU486. These results indicate that the actions of both follicular and luteal progesterone synergize in maintaining the length of the estrous cycle in 5-day cyclic rats and that functionally active CL increase progesterone production only under the action of a complete surge of prolactin.

Animals↗

PubMed1995

Luteinizing hormone (LH) and corticosterone in proestrous afternoon restore the follicle-stimulating hormone secretion at early estrus in adrenalectomized LH-releasing hormone antagonist-treated rats.

Administration of the antiprogestagen RU486 in the morning of proestrus abolishes the secondary surge of FSH during early estrus in the rat without preventing the drop in serum inhibin. In addition, the injection of an ovulatory dose of LH to RU486-injected rats does not restore the secondary surge of FSH. Since RU486 is a potent antiprogesterone with antiglucocorticoid activity, in the first experiment we compared the effects of RU486 and a specific antiprogesterone serum (APS), administered on proestrus, on the secretion of FSH during early estrus. While RU486 and APS reduced the primary surge of LH and FSH, only RU486 abolished the secondary secretion of FSH. In the second experiment, rats injected with LHRH antagonist (LHRHa) and ovine LH (oLH) were adrenalectomized (ADX) or sham-ADX in the morning and injected with corticosterone (B) or oil in the afternoon of proestrus. LHRHa completely eliminated, and oLH restored, the secretion of FSH at 0200 h in estrus. ADX reduced FSH serum concentration at 0200 h in estrus, and B reversed this effect in rats injected with LHRHa and oLH. The results of these experiments indicate that, in the rat, the LHRH-independent secretion of FSH during early estrus is evoked by the combined effects of the preovulatory surge of LH and the rise in serum B on proestrous afternoon.

Adrenal Glands↗

PubMed1995

Follicular and luteal progesterone play different roles synchronizing pituitary and ovarian events in the 4-day cyclic rat.

Administration of 4 mg of the antiprogestagen RU486 to 4-day cyclic rats during proestrus induced a 1-day shortening of the ovarian cycle, a reduction in ovulatory rate that was reversed by an injection of exogenous human (h)FSH in the evening of proestrus, and the absence of the LH-inhibiting effect of exogenous estradiol resulting in a 24-h advancement of the preovulatory LH surge. These effects were not present when RU486 was injected during estrus. RU486 injected during either proestrus or estrus increased serum levels of LH and estradiol-17 beta in diestrus and reduced the magnitude of the preovulatory surge of gonadotropins. Only rats treated with RU486 during estrus showed increased follicular size and acceleration of oocyte maturation on proestrous afternoon. These results demonstrate that in 4-day cyclic rats receiving an injection of RU486 during proestrus, the low ovulatory rate is a consequence of a reduced secondary FSH surge-induced follicular recruitment in the afternoon of estrus and that the shortening of the estrous cycle is the result of an advanced desensitization to the negative feedback of estradiol on LH secretion. Furthermore, since the administration of RU486 during proestrus blocks both follicular and luteal progesterone actions whereas injection during estrus blocks only luteal progesterone actions, we suggest that, in 4-day cyclic rats, the actions of progesterone during diestrus retard maturation of follicles via the lowering of serum LH concentrations and that the actions of progesterone in proestrous evening delay the desensitization to the negative estrogen feedback on LH secretion.

Animals↗

PubMed1995

One day estrous cycle shortening induced by antiprogestagen RU486 administration in proestrus to 4-day cyclic rats.

Administration of 4 mg of the antiprogestagen RU486 to 4-day cyclic rats in proestrus, which blocks proestrous and diestrous progesterone actions, induced a one day shortening of the ovarian cycle and a reduction of the ovulation rate in the following cycle. These effects were not present when RU486 was administered in estrus or metestrus. RU486 injections either in proestrus or estrus increased the serum levels of LH and 17 beta-estradiol during metestrus. However, only rats injected with RU486 in proestrus presented a 24 hour advancement of the preovulatory surge of gonadotropins and a lack of the LH-inhibiting effect of exogenous estradiol. These results suggest that, in 4-day cyclic rats, the secretion of progesterone by the corpora lutea during diestrous phase retards the follicular development by lowering the serum concentrations of LH, whereas progesterone secretion by the preovulatory follicles in proestrus regulates the estrous cycle length by antagonizing the desensitization of the pituitary to the estrogen negative feedback on LH secretion.

Animals↗

PubMed1994

Inappropriate ovarian feedback in basal gonadotropin secretion in 4-day cyclic rat treated with mifepristone: role of endogenous estradiol.

Administration of the antiprogesterone RU486 to 4-day cyclic rats from metestrus onwards resulted in a dissociation of basal LH and FSH secretion and ovariectomy abolished this effect of RU486. Since RU486 also induces abnormally high concentrations of testosterone without affecting estradiol concentrations during the diestrous phase, we have studied the involvement of androgen or estrogen in RU486-dissociated gonadotropin secretions. Ovariectomized- (OVX) or sham-OVX rats at 08:00 h in metestrus were injected with RU486 (2 mg) or vehicle (0.2 ml) at 08:00 and 17:00 h in metestrus (day 1) and diestrus (day 2). Also, OVX-and sham-OVX rats injected with RU486 or oil were, in addition, treated with the antiandrogen flutamide and/or the antiestrogen tamoxifen (1 mg/0.2 ml) at 08:00 and 17:00 on days 1 and 2. The serum concentrations of LH and FSH were determined at 08:00 and 17:00 h on days 1 and 2 and at 08:00 h on day 3. OVX completely reversed the effects of RU486 on basal gonadotropin secretions while flutamide treatment affected neither LH nor FSH in any of the groups studied. On the contrary, tamoxifen treatment in RU486-injected rats reduced the LH concentrations to the levels found in OVX-rats and increased FSH concentrations to the levels in sham-OVX rats. Since the doses of flutamide and tamoxifen used block the action of androgens and estrogens, respectively, the results of this study evidence that endogenous estradiol in the absence of the effects of progesterone at both hypothalamus-pituitary and ovary levels stimulates LH and inhibits FSH secretion during the low secretion rate of gonadotropins in the rat.

Animals↗

PubMed1994

Periovulatory LHRH, LH and FSH secretion in cyclic rats treated with RU486: effects of exogenous LHRH and LHRH antagonist on LH and FSH secretion at early oestrus.

The antiprogesterone RU486 injected on the morning of pro-oestrus blunts the preovulatory secretion of LH and FSH and abolishes the secondary secretion of FSH during oestrus without affecting ovulation in the rat. To ascertain whether the secretion of LHRH is involved in these effects, we studied the effects of RU486 (4 mg/0.2 ml oil), given s.c. at 0800 h on pro-oestrus, on LHRH secretion into the pituitary stalk blood vessels and on peripheral plasma concentrations of LH and FSH at 1800 h on pro-oestrus and 0200 h on oestrus. Furthermore, we determined the effects of an s.c. injection of 1 mg of an LHRH antagonist (LHRH-A; ORG30276) at 2000 h on pro-oestrus and those of an i.p. injection of 100 ng LHRH (Peninsula 7201) at 0100 h on oestrus on serum concentrations of LH, FSH and oestradiol at 0200 h on oestrus in oil- and RU486-treated rats. RU486 decreased LHRH secretion at 1800 h on pro-oestrus while this was increased at 0200 h on oestrus. While the reduction of preovulatory LHRH secretion in RU486-treated rats coincided with a reduction in both LH and FSH surges during the evening of pro-oestrus, the increased LHRH secretion during the early hours of oestrus was only accompanied by an increased concentration of LH. An injection of LHRH stimulated, while that of LHRH-A inhibited serum concentrations of LH at 0200 h on oestrus in both oil- and RU486-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗