Biomedical subjects

M Tébar

Publications and source records attributed to M Tébar.

22 records · Page 2Linked to original sources

PubMed1994

Effect of antiprogestagen RU486 on both natural and prolactin-induced morphological luteolysis in rat..

Adult female cyclic rats were hypophysectomized and their pituitary glands autotransplanted beneath the left kidney capsule (Aptr) on day 1 (metestrus). To induce the luteolytic effect of prolactin (PRL) the rats were injected s.c. with 0.4 mg of 2-bromo-alpha-ergocryptine (CB154) on cycle days 12, 13 and 14. Other groups of Aptr rats were injected daily with CB154 or ethanol vehicle from day 12 to day 23. To study the role of progesterone (P) on the luteotrophic effect of PRL as well as on the natural and on the PRL-induced luteolysis, rats without CB154 treatment or with long or short CB154 treatment were injected s. c. with 2 mg of the antiprogestagen RU486 or 0.1 ml oil from day 1 to day 23. From each rat the mean weight of the corpus luteum (CL) was noted on day 24. The serum PRL level rose from day 1 to day 12 and fell thereafter by day 15 in CB154-treated rats. The serum level of PRL rose again in short term CB154-treated rats, and remained low in long term CB154-treated rats. No effect of RU486 on serum PRL levels was noted in any group. The serum P level fell rapidly as the treatment with CB154 began after day 12. Neither the rise in serum PRL after day 15 in short term CB154-treated rats nor RU486 treatment affected the P level. Treatment with RU486 did not affect the CL weight on day 24 in ethanol vehicle injected rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Hypothalamus-pituitary-ovarian axis in cyclic rats lacking progesterone actions.

Antagonizing diestrous progesterone actions in cyclic rats by s.c. injections of the antiprogesterone RU486 (2 mg twice a day from metestrus through proestrus) increased LH and decreased FSH basal serum concentrations. Ovariectomy at metestrus (0800 h) increased serum levels of both gonadotropins in controls and reversed the RU486-induced dissociation of basal gonadotropin secretion. RU486-dissociated gonadotropin secretion is also dependent upon LHRH, since treatment (s.c.) with 1 mg GnRH antagonist (ORG 30276) twice a day on metestrus and diestrus completely prevented both the RU486-induced increase in LH and the decrease in FSH serum concentrations. The LHRH content in the medial basal hypothalamus and median eminence increased on proestrous morning in RU486-treated rats. The LH pituitary response to an exogenous i.v. bolus of 25 ng LHRH (Peninsula 7201; Peninsula Laboratory, Inc., Merseyside, UK) at 1700 h on diestrus was enhanced in rats treated with RU486. No differences in pituitary FSH response were noted with respect to oil-injected rats. The pituitary content of both gonadotropins decreased in RU486-treated rats on proestrous morning. All these effects due to RU486 in cyclic rats were reversed by ovariectomy. Testosterone serum levels increased significantly from diestrus onward, and the estradiol concentration increased on proestrous morning in RU486-treated rats. Ovariectomy as well as LHRH antagonist treatment eliminated the effects of RU486 on ovarian steroid production. Moreover, antiestrogen tamoxifen treatment reversed RU486-dissociated gonadotropin secretion, while antiandrogen flutamide treatment had no effect. The results of this experiment have confirmed previous findings that RU486 treatment dissociates basal gonadotropin secretion in cyclic rats. In addition, the present results show that: (1) this effect of RU486 is not due to a direct effect of this compound or to the blockade of progesterone action at a central level; (2) the effect of RU486 on pituitary gonadotropin secretion depends on ovarian substances other than progesterone and LHRH, since it is reversed by ovariectomy and completely abolished by LHRH antagonist treatment; (3) the reduction in FSH serum levels in rats treated with RU486 seems to be exerted by inhibin and estradiol at the pituitary level by reducing FSH synthesis and secretion; and (4) the hypersecretion of LH in rats treated with RU486, as compared to that resulting from ovariectomy, seems to be the consequence of, first, a lack of progesterone inhibitory action on LH secretion, and, second, an inappropriate feedback system involving increased hypothalamic LHRH activity and pituitary sensitivity to LHRH of moderately high levels of estradiol in the presence of abnormally high levels of testosterone.

Amino Acid Sequence↗

PubMed1993

Evidence that androgens are involved in atresia and anovulation induced by antiprogesterone RU486 in rats.

Administration of antiprogesterone RU486 to female cyclic rats results in blockade of ovulation associated with both a decreased ovulatory release of LH and an increased rate of follicular atresia. These rats also exhibit increased LH:FSH and testosterone:oestradiol ratios in serum during the period of follicular development as well as an increase in serum concentrations of prolactin that can be suppressed by a dopamine agonist. The increase in either prolactin or testosterone concentrations as well as the relative deficiency in FSH might be responsible for the increase in follicular atresia. The present work evaluated the involvement of LH, FSH, prolactin and testosterone in follicular atresia and in blockade of ovulation induced by RU486 in the cyclic rat. Although bromocriptine treatment did not modify the blockade of ovulation induced by RU486, unilateral ovariectomy at metoestrus and anti-androgen flutamide treatment reversed, in part, the effects of RU486 on both follicular development and ovulation. The combined increase in FSH serum concentration during dioestrus induced by unilateral ovariectomy and the treatment with flutamide had no additive effects. Furthermore, treatment with a superovulatory amount of hFSH did not reverse the effects of RU486. Moreover, unilateral ovariectomy halved testosterone serum concentrations and flutamide treatment had no effect on LH and FSH concentrations in RU486-treated rats. It was therefore concluded that androgens play a role, at least in part, in the process of follicular atresia induced by RU486.

Androgens↗

PubMed1992

Unilateral ovariectomy, flutamide treatment and HCG reverse the anovulatory action of antiprogesterone RU486 in rat.

Administration of antiprogesterone RU486 (4 mg/day) from estrus through proestrus to cyclic rats blocked ovulation. Moreover, RU486 increased basal serum concentrations of LH, PRL, testosterone and estradiol, while it decreased basal serum concentration of FSH. Both unilateral ovariectomy and antiandrogen flutamide treatment, as well as an ovulatory injection of HCG in the proestrus afternoon partially reversed, the ovulatory blockade of RU486. These results indicate that both the decreased FSH concentration and the increased testosterone concentration, as well as the reduced ovulatory LH release are responsible for the anovulatory effects of RU486.

Animals↗