Effects of RU486 on the ovarian response of immature rats to pregnant mare's serum gonadotrophin or diethylstilbestrol

M. L. Forcelledo; L. Leiva; H. B. Croxatto

doi:10.1093/oxfordjournals.humrep.a138315

Effects of RU486 on the ovarian response of immature rats to pregnant mare's serum gonadotrophin or diethylstilbestrol

M. L. Forcelledo, L. Leiva, H. B. Croxatto

Medicine School

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

The purpose of this study was to further investigate the role of progesterone in follicular development induced by pregnant mare serum gonadotrophin (PMSG) or diethylstilbestrol (DES), in pre-pubertal rats, using RU486 to prevent the receptor-mediated actions of progesterone. Intact or hypophysectomized 26-day-old rats received either a single injection of 10 IU PMSG i.p., or 2 mg DES s.c. daily for 3 days, with or without 0.8 mg RU486 s.c. daily for 3 days. Groups of rats were killed 51-96 h after the first injection. RU486 significantly increased the ovarian weight gain, the ovarian and circulating concentrations of progesterone, the concentrations of immunoreactive and bioactive LH and the number of ovulated oocytes in intact rats. RU486 did not affect the ovarian weight increase induced by PMSG or the ovulatory response following PMSG plus human chorionic gonadotrophin (HCG) in rats hypophysectomized 24 h before initiating treatment or in intact rats where ovulation was blocked with chlorpromazine. The ovarian weight gain, the development of antral follicles and the increments in tissue and plasma progesterone concentrations and luteinizing hormone (LH) plasma concentrations elicited by DES in intact rats, were further increased by concomitant treatment with RU486, whereas the ovarian weight increase and antral follicle development induced by DES were completely inhibited by RU486 in hypophysectomized rats. Follicles stimulated to grow by DES plus RU486, but not by DES alone, were capable of ovulating in response to HCG. These results show that ovarian growth and follicular development induced by exogenous gonadotrophin or oestrogen in the immature rat are enhanced by RU486 and that this synergistic effect of the progesterone receptor blocker is either pituitary-mediated or requires the permissive action of a pituitary factor. Overall they support a negative effect of progesterone on follicular development in the rat.

Original language	English
Pages (from-to)	24-31
Number of pages	8
Journal	Human Reproduction
Volume	9
Issue number	1
DOIs	https://doi.org/10.1093/oxfordjournals.humrep.a138315
Publication status	Published - Jan 1994

Keywords

Antiprogestin
Follicular development
Ovulation
Progesterone
Rat

ASJC Scopus subject areas

Reproductive Medicine
Obstetrics and Gynaecology

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10.1093/oxfordjournals.humrep.a138315

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@article{42a80d30ae5a40048a88933c07fa577c,

title = "Effects of RU486 on the ovarian response of immature rats to pregnant mare's serum gonadotrophin or diethylstilbestrol",

abstract = "The purpose of this study was to further investigate the role of progesterone in follicular development induced by pregnant mare serum gonadotrophin (PMSG) or diethylstilbestrol (DES), in pre-pubertal rats, using RU486 to prevent the receptor-mediated actions of progesterone. Intact or hypophysectomized 26-day-old rats received either a single injection of 10 IU PMSG i.p., or 2 mg DES s.c. daily for 3 days, with or without 0.8 mg RU486 s.c. daily for 3 days. Groups of rats were killed 51-96 h after the first injection. RU486 significantly increased the ovarian weight gain, the ovarian and circulating concentrations of progesterone, the concentrations of immunoreactive and bioactive LH and the number of ovulated oocytes in intact rats. RU486 did not affect the ovarian weight increase induced by PMSG or the ovulatory response following PMSG plus human chorionic gonadotrophin (HCG) in rats hypophysectomized 24 h before initiating treatment or in intact rats where ovulation was blocked with chlorpromazine. The ovarian weight gain, the development of antral follicles and the increments in tissue and plasma progesterone concentrations and luteinizing hormone (LH) plasma concentrations elicited by DES in intact rats, were further increased by concomitant treatment with RU486, whereas the ovarian weight increase and antral follicle development induced by DES were completely inhibited by RU486 in hypophysectomized rats. Follicles stimulated to grow by DES plus RU486, but not by DES alone, were capable of ovulating in response to HCG. These results show that ovarian growth and follicular development induced by exogenous gonadotrophin or oestrogen in the immature rat are enhanced by RU486 and that this synergistic effect of the progesterone receptor blocker is either pituitary-mediated or requires the permissive action of a pituitary factor. Overall they support a negative effect of progesterone on follicular development in the rat.",

keywords = "Antiprogestin, Follicular development, Ovulation, Progesterone, Rat",

author = "Forcelledo, {M. L.} and L. Leiva and Croxatto, {H. B.}",

note = "Funding Information: We gratefully acknowledge the generous gift of anti-LH rat antibody and rLH-RP3 from the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIDDK). Reagents for progesterone, oestradiol and testosterone radioimmunoassay and human LH standard were provided by the World Health Organization Programme for the Provision of Matched Reagents for the Radioimmunoassay of Hormones in Reproductive Physiology. The authors are grateful to Mrs A.Brandeis, C.Llados, E. Nunez and G.Bravo for performing the steroid assays and Mrs A.Zepeda for the statistical analysis. This research was supported by FONDECYT 0918 and 0083 and The Rockefeller Foundation, RF 91032.",

year = "1994",

month = jan,

doi = "10.1093/oxfordjournals.humrep.a138315",

language = "English",

volume = "9",

pages = "24--31",

journal = "Human Reproduction",

issn = "0268-1161",

publisher = "Oxford University Press",

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T1 - Effects of RU486 on the ovarian response of immature rats to pregnant mare's serum gonadotrophin or diethylstilbestrol

AU - Forcelledo, M. L.

AU - Leiva, L.

AU - Croxatto, H. B.

N1 - Funding Information: We gratefully acknowledge the generous gift of anti-LH rat antibody and rLH-RP3 from the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIDDK). Reagents for progesterone, oestradiol and testosterone radioimmunoassay and human LH standard were provided by the World Health Organization Programme for the Provision of Matched Reagents for the Radioimmunoassay of Hormones in Reproductive Physiology. The authors are grateful to Mrs A.Brandeis, C.Llados, E. Nunez and G.Bravo for performing the steroid assays and Mrs A.Zepeda for the statistical analysis. This research was supported by FONDECYT 0918 and 0083 and The Rockefeller Foundation, RF 91032.

PY - 1994/1

Y1 - 1994/1

N2 - The purpose of this study was to further investigate the role of progesterone in follicular development induced by pregnant mare serum gonadotrophin (PMSG) or diethylstilbestrol (DES), in pre-pubertal rats, using RU486 to prevent the receptor-mediated actions of progesterone. Intact or hypophysectomized 26-day-old rats received either a single injection of 10 IU PMSG i.p., or 2 mg DES s.c. daily for 3 days, with or without 0.8 mg RU486 s.c. daily for 3 days. Groups of rats were killed 51-96 h after the first injection. RU486 significantly increased the ovarian weight gain, the ovarian and circulating concentrations of progesterone, the concentrations of immunoreactive and bioactive LH and the number of ovulated oocytes in intact rats. RU486 did not affect the ovarian weight increase induced by PMSG or the ovulatory response following PMSG plus human chorionic gonadotrophin (HCG) in rats hypophysectomized 24 h before initiating treatment or in intact rats where ovulation was blocked with chlorpromazine. The ovarian weight gain, the development of antral follicles and the increments in tissue and plasma progesterone concentrations and luteinizing hormone (LH) plasma concentrations elicited by DES in intact rats, were further increased by concomitant treatment with RU486, whereas the ovarian weight increase and antral follicle development induced by DES were completely inhibited by RU486 in hypophysectomized rats. Follicles stimulated to grow by DES plus RU486, but not by DES alone, were capable of ovulating in response to HCG. These results show that ovarian growth and follicular development induced by exogenous gonadotrophin or oestrogen in the immature rat are enhanced by RU486 and that this synergistic effect of the progesterone receptor blocker is either pituitary-mediated or requires the permissive action of a pituitary factor. Overall they support a negative effect of progesterone on follicular development in the rat.

AB - The purpose of this study was to further investigate the role of progesterone in follicular development induced by pregnant mare serum gonadotrophin (PMSG) or diethylstilbestrol (DES), in pre-pubertal rats, using RU486 to prevent the receptor-mediated actions of progesterone. Intact or hypophysectomized 26-day-old rats received either a single injection of 10 IU PMSG i.p., or 2 mg DES s.c. daily for 3 days, with or without 0.8 mg RU486 s.c. daily for 3 days. Groups of rats were killed 51-96 h after the first injection. RU486 significantly increased the ovarian weight gain, the ovarian and circulating concentrations of progesterone, the concentrations of immunoreactive and bioactive LH and the number of ovulated oocytes in intact rats. RU486 did not affect the ovarian weight increase induced by PMSG or the ovulatory response following PMSG plus human chorionic gonadotrophin (HCG) in rats hypophysectomized 24 h before initiating treatment or in intact rats where ovulation was blocked with chlorpromazine. The ovarian weight gain, the development of antral follicles and the increments in tissue and plasma progesterone concentrations and luteinizing hormone (LH) plasma concentrations elicited by DES in intact rats, were further increased by concomitant treatment with RU486, whereas the ovarian weight increase and antral follicle development induced by DES were completely inhibited by RU486 in hypophysectomized rats. Follicles stimulated to grow by DES plus RU486, but not by DES alone, were capable of ovulating in response to HCG. These results show that ovarian growth and follicular development induced by exogenous gonadotrophin or oestrogen in the immature rat are enhanced by RU486 and that this synergistic effect of the progesterone receptor blocker is either pituitary-mediated or requires the permissive action of a pituitary factor. Overall they support a negative effect of progesterone on follicular development in the rat.

KW - Antiprogestin

KW - Follicular development

KW - Ovulation

KW - Progesterone

KW - Rat

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Effects of RU486 on the ovarian response of immature rats to pregnant mare's serum gonadotrophin or diethylstilbestrol

Abstract

Keywords

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