Animal studies on the endocrinological profile of dienogest, a novel synthetic steroid

Y. Katsuki, S. Sasagawa, Y. Takano, Y. Shibutani, Daisuke Aoki, Y. Udagawa, S. Nozawa

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Dienogest is an orally active synthetic steroid that is used for contraception and is currently being studied for the possible treatment of endometriosis. Earlier we demonstrated that dienogest had therapeutic effects on experimental endometriosis in rats and that its mechanisms of action were different from those of drugs currently on the market for the treatment of endometriosis. We also reported preclinically that dienogest showed a potential anticancer action against hormone-dependent cancers that was different from that of progestins. Accordingly we obtained preclinical background data for the above-described clinical applications and extension of the clinical use of the drug in the near future by investigating the endocrinological profile of dienogest in rabbits and rats. Dienogest was characterized by having a moderate binding affinity for progesterone receptors and by progestational activities: it stimulated endometrial proliferation (≤ 0.01 mg/kg) that was only partially inhibited by RU-486, and induced carbonic anhydrase activity in endometrium (≤ 0.01 mg/kg). Also, it was slightly uterotrophic (≤ 1 mg/kg) with very low binding affinity for oestrogen receptors and slightly antioestrogenic (≤ 1 mg/kg). In addition, dienogest showed slight binding to androgen receptors but without biological androgenic and anabolic activities (100 mg/kg), with neither glucocorticoid activity nor mineralocorticoid activity (100 mg/kg), and with very slight binding affinity for human sex hormone-binding globulin. These findings suggest that dienogest is not a pure progestin and appears to induce fewer side effects than drugs currently on the market for the treatment of endometriosis.

Original languageEnglish
Pages (from-to)45-62
Number of pages18
JournalDrugs under Experimental and Clinical Research
Volume23
Issue number2
Publication statusPublished - 1997

Fingerprint

dienogest
Steroids
Endometriosis
Progestins
Mifepristone
Mineralocorticoids
Sex Hormone-Binding Globulin
Carbonic Anhydrases
Androgen Receptors
Therapeutic Uses
Progesterone Receptors
Endometrium
Drug-Related Side Effects and Adverse Reactions
Contraception
Estrogen Receptors
Pharmaceutical Preparations
Glucocorticoids
Action Potentials

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology (medical)
  • Pharmacology
  • Drug Discovery

Cite this

Katsuki, Y., Sasagawa, S., Takano, Y., Shibutani, Y., Aoki, D., Udagawa, Y., & Nozawa, S. (1997). Animal studies on the endocrinological profile of dienogest, a novel synthetic steroid. Drugs under Experimental and Clinical Research, 23(2), 45-62.

Animal studies on the endocrinological profile of dienogest, a novel synthetic steroid. / Katsuki, Y.; Sasagawa, S.; Takano, Y.; Shibutani, Y.; Aoki, Daisuke; Udagawa, Y.; Nozawa, S.

In: Drugs under Experimental and Clinical Research, Vol. 23, No. 2, 1997, p. 45-62.

Research output: Contribution to journalArticle

Katsuki, Y, Sasagawa, S, Takano, Y, Shibutani, Y, Aoki, D, Udagawa, Y & Nozawa, S 1997, 'Animal studies on the endocrinological profile of dienogest, a novel synthetic steroid', Drugs under Experimental and Clinical Research, vol. 23, no. 2, pp. 45-62.
Katsuki, Y. ; Sasagawa, S. ; Takano, Y. ; Shibutani, Y. ; Aoki, Daisuke ; Udagawa, Y. ; Nozawa, S. / Animal studies on the endocrinological profile of dienogest, a novel synthetic steroid. In: Drugs under Experimental and Clinical Research. 1997 ; Vol. 23, No. 2. pp. 45-62.
@article{bfdad5f8876646069e158f1734fc9392,
title = "Animal studies on the endocrinological profile of dienogest, a novel synthetic steroid",
abstract = "Dienogest is an orally active synthetic steroid that is used for contraception and is currently being studied for the possible treatment of endometriosis. Earlier we demonstrated that dienogest had therapeutic effects on experimental endometriosis in rats and that its mechanisms of action were different from those of drugs currently on the market for the treatment of endometriosis. We also reported preclinically that dienogest showed a potential anticancer action against hormone-dependent cancers that was different from that of progestins. Accordingly we obtained preclinical background data for the above-described clinical applications and extension of the clinical use of the drug in the near future by investigating the endocrinological profile of dienogest in rabbits and rats. Dienogest was characterized by having a moderate binding affinity for progesterone receptors and by progestational activities: it stimulated endometrial proliferation (≤ 0.01 mg/kg) that was only partially inhibited by RU-486, and induced carbonic anhydrase activity in endometrium (≤ 0.01 mg/kg). Also, it was slightly uterotrophic (≤ 1 mg/kg) with very low binding affinity for oestrogen receptors and slightly antioestrogenic (≤ 1 mg/kg). In addition, dienogest showed slight binding to androgen receptors but without biological androgenic and anabolic activities (100 mg/kg), with neither glucocorticoid activity nor mineralocorticoid activity (100 mg/kg), and with very slight binding affinity for human sex hormone-binding globulin. These findings suggest that dienogest is not a pure progestin and appears to induce fewer side effects than drugs currently on the market for the treatment of endometriosis.",
author = "Y. Katsuki and S. Sasagawa and Y. Takano and Y. Shibutani and Daisuke Aoki and Y. Udagawa and S. Nozawa",
year = "1997",
language = "English",
volume = "23",
pages = "45--62",
journal = "Drugs under Experimental and Clinical Research",
issn = "0378-6501",
publisher = "Bioscience Ediprint Inc.",
number = "2",

}

TY - JOUR

T1 - Animal studies on the endocrinological profile of dienogest, a novel synthetic steroid

AU - Katsuki, Y.

AU - Sasagawa, S.

AU - Takano, Y.

AU - Shibutani, Y.

AU - Aoki, Daisuke

AU - Udagawa, Y.

AU - Nozawa, S.

PY - 1997

Y1 - 1997

N2 - Dienogest is an orally active synthetic steroid that is used for contraception and is currently being studied for the possible treatment of endometriosis. Earlier we demonstrated that dienogest had therapeutic effects on experimental endometriosis in rats and that its mechanisms of action were different from those of drugs currently on the market for the treatment of endometriosis. We also reported preclinically that dienogest showed a potential anticancer action against hormone-dependent cancers that was different from that of progestins. Accordingly we obtained preclinical background data for the above-described clinical applications and extension of the clinical use of the drug in the near future by investigating the endocrinological profile of dienogest in rabbits and rats. Dienogest was characterized by having a moderate binding affinity for progesterone receptors and by progestational activities: it stimulated endometrial proliferation (≤ 0.01 mg/kg) that was only partially inhibited by RU-486, and induced carbonic anhydrase activity in endometrium (≤ 0.01 mg/kg). Also, it was slightly uterotrophic (≤ 1 mg/kg) with very low binding affinity for oestrogen receptors and slightly antioestrogenic (≤ 1 mg/kg). In addition, dienogest showed slight binding to androgen receptors but without biological androgenic and anabolic activities (100 mg/kg), with neither glucocorticoid activity nor mineralocorticoid activity (100 mg/kg), and with very slight binding affinity for human sex hormone-binding globulin. These findings suggest that dienogest is not a pure progestin and appears to induce fewer side effects than drugs currently on the market for the treatment of endometriosis.

AB - Dienogest is an orally active synthetic steroid that is used for contraception and is currently being studied for the possible treatment of endometriosis. Earlier we demonstrated that dienogest had therapeutic effects on experimental endometriosis in rats and that its mechanisms of action were different from those of drugs currently on the market for the treatment of endometriosis. We also reported preclinically that dienogest showed a potential anticancer action against hormone-dependent cancers that was different from that of progestins. Accordingly we obtained preclinical background data for the above-described clinical applications and extension of the clinical use of the drug in the near future by investigating the endocrinological profile of dienogest in rabbits and rats. Dienogest was characterized by having a moderate binding affinity for progesterone receptors and by progestational activities: it stimulated endometrial proliferation (≤ 0.01 mg/kg) that was only partially inhibited by RU-486, and induced carbonic anhydrase activity in endometrium (≤ 0.01 mg/kg). Also, it was slightly uterotrophic (≤ 1 mg/kg) with very low binding affinity for oestrogen receptors and slightly antioestrogenic (≤ 1 mg/kg). In addition, dienogest showed slight binding to androgen receptors but without biological androgenic and anabolic activities (100 mg/kg), with neither glucocorticoid activity nor mineralocorticoid activity (100 mg/kg), and with very slight binding affinity for human sex hormone-binding globulin. These findings suggest that dienogest is not a pure progestin and appears to induce fewer side effects than drugs currently on the market for the treatment of endometriosis.

UR - http://www.scopus.com/inward/record.url?scp=0031349971&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031349971&partnerID=8YFLogxK

M3 - Article

C2 - 9309380

AN - SCOPUS:0031349971

VL - 23

SP - 45

EP - 62

JO - Drugs under Experimental and Clinical Research

JF - Drugs under Experimental and Clinical Research

SN - 0378-6501

IS - 2

ER -