Growth-stimulating effect of dienogest, a synthetic steroid, on rodent, canine, and primate mammary glands

Tsutomu Ishikawa; Seiji Inoue; Chihaya Kakinuma; Chitose Kuwayama; Yoshimasa Hamada; Yasunori Shibutani

doi:10.1016/s0300-483x(00)00318-8

Growth-stimulating effect of dienogest, a synthetic steroid, on rodent, canine, and primate mammary glands

Tsutomu Ishikawa, Seiji Inoue, Chihaya Kakinuma, Chitose Kuwayama, Yoshimasa Hamada, Yasunori Shibutani

In: Toxicology · 2000 · vol. 151(1-3) , pp. 91–101 · doi:10.1016/s0300-483x(00)00318-8 · PMID:11074304 · W1986532755

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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

Dienogest, a synthetic steroid, was found to stimulate mammary gland growth in rodent, canine, and primate models.

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Abstract

We observed hyperplasia of the mammary gland in female beagle dogs, but not in female rats and monkeys, in 91-day toxicity studies on dienogest. In order to elucidate a possible mechanism for its development and to account for this species difference, we determined the plasma level of growth hormone (GH) in dogs, rats, and monkeys treated orally with dienogest for 91 days. As a result, dogs with mammary hyperplasia showed a prominent, dose-dependent increase in their GH level; and, contrarily, rats and monkeys without the hyperplasia of this organ failed to show any such increase. These results were supported by evidence from immunohistochemical and morphometric analysis of the pituitary gland. In addition, dienogest and medroxyprogesterone acetate (MPA) stimulated the growth of canine mammary epithelial cells in the presence of estradiol in vitro, but had no effect on rat and human mammary epithelial cells incubated under the same conditions. In conclusion, dienogest with progestational activity caused proliferation of the mammary gland in beagle dogs by increasing the secretion of GH, as do other progestational compounds. This change may be partially dependent on the direct effect of the drug.

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Cites (2)

References (11)

Animal studies on the endocrinological profile of dienogest, a novel synthetic steroid. via openalex
Effects of dienogest, a synthetic steroid, on experimental endometriosis in rats via openalex
doi:10.1016/s0015-0282(16)45741-9 via openalex
doi:10.1016/0002-9378(77)90295-2 via openalex
doi:10.1177/019262338901700216 via openalex
W1626257761 via openalex
doi:10.1055/s-0029-1210224 via openalex
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doi:10.1016/0027-5107(91)90067-x via openalex
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SciLite annotations

chemicals 8

dienogest steroid dienogest dienogest medroxyprogesterone acetate estradiol dienogest

organisms 11

rodents primates dogs rattus sp. old world monkeys dogs rattus sp. old world monkeys zitter rats human dogs

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[1] Effects of dienogest, a synthetic steroid, on experimental endometriosis in rats 1998

[2] Animal studies on the endocrinological profile of dienogest, a novel synthetic steroid. 1997