RU 38486: An Original Multifaceted Antihormone in Vivo

Philibert, D.

doi:10.1515/9783110809572-004

Cited by 115 publications

(96 citation statements)

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“…Because of this, the effects of RU486 on FSH and LH secretion in males should be the result of either the blockade of the feedback effect of peripheral glands at the pituitary level and/or a change of pituitary responsiveness to LHRH. Besides the antiprogestagenic activity, the synthetic steroid RU486 also has strong antiglucocorticoid and moderate antiandrogenic activity (Philibert 1984). In male rats adrenal secretory products play a modulatory role in the secretion of FSH and LH (Lorenzen et al 1980).…”

Section: Discussionmentioning

confidence: 99%

“…This compound has a high affinity for progesterone and glucocorticoid receptors (Philibert 1984, Baulieu 1989. Injections consisted of 4 mg/0·2 ml oil (s.c.).…”

Section: Drugs Treatment and Surgerymentioning

confidence: 99%

“…The antiprogestagen RU486 is a synthetic steroid with strong antiprogesterone and antiglucocorticoid activity (Philibert 1984, Baulieu 1989. It has been shown that administration of RU486 to female cyclic rats dissociates dioestrous secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) (Sánchez-Criado et al 1990, reduces the magnitude of the preovulatory LH surge (Rao & Mahesh 1986, Sánchez-Criado et al 1990) and abolishes the primary and secondary surge of FSH (Knox & Schwartz 1992, Knox et al 1993, Sánchez-Criado et al 1994.…”

Section: Introductionmentioning

confidence: 99%

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

Sánchez-Criado¹,

Bellido²,

Tébar³

et al. 1999

Journal of Endocrinology

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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 LHRHstimulated LH secretion at the pituitary level, and that FSH secretion increased in response to a reduction in the negative feedback of androgen.

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Section: Discussionmentioning

confidence: 99%

“…This compound has a high affinity for progesterone and glucocorticoid receptors (Philibert 1984, Baulieu 1989. Injections consisted of 4 mg/0·2 ml oil (s.c.).…”

Section: Drugs Treatment and Surgerymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Sánchez-Criado¹,

Bellido²,

Tébar³

et al. 1999

Journal of Endocrinology

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show abstract

“…The primary action of progesterone is to initiate and maintain pregnancy. Progesterone, the natural ligand of the PR, represents the pure agonist, onapristone, mifepristone show a pure antagonist activity and asoprisnil exhibits partial agonist/antagonist effects [1].The synthesis of mifepristone, the first PR antagonist (PA) was a starting point of drug discovery and the research programme in the area of PAs [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

“…separate from decidua [2,[15][16][17]. Mifepristone sensitises the pregnant uterus and cervix to endogenous and exogenous prostaglandins, increasing uterine activity and inducing cervical softening.…”

Section: Introductionmentioning

confidence: 99%