title: Effect of SMP-028 on steroidogenesis in rats; mechanism of toxicological events on endocrine organs of rats.
abstract: SMP-028 is a new compound for treatment of asthma. Oral administration of SMP-028 to rats was associated with toxicological events in endocrine organs. These events mainly consisted of pathological changes in the adrenal gland, testis, prostate, seminal vesicle, ovaries, and uterus. In this study, we set to clarify whether SMP-028 inhibits steroidogenesis in primary culture cells obtained from rat endocrine organs in vitro. Adrenal cells, testicular cells, and ovarian cells were treated with SMP-028 and the production of steroid hormones, i.e., progesterone, aldosterone, corticosterone, total testosterone, and estradiol from these cells was measured by radioimmunoassay. We found that the production of progesterone from these cells treated with SMP-028 at 1 μM decreased to 16-67% that of the control. These findings indicate that SMP-028 inhibits steroidogenesis in rat endocrine organs in vitro. Considering that free maximum concentration in rats treated with SMP-028 are higher than the IC50 values for the inhibition of steroidogenesis in vitro, it is therefore believed that the toxicological events seen in rats following treatment with SMP-028 are due to inhibition of steroidogenesis in vivo.
authors.affiliation: Preclinical Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Japan. Electronic address: yohei-nishizato@ds-pharma.co.jp.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Nishizato
authors.affiliation: Preclinical Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Japan.
authors.forename: Satoki
authors.initials: S
authors.lastname: Imai
authors.affiliation: Preclinical Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yabunaka
authors.affiliation: Research Planning & Intelligence, Dainippon Sumitomo Pharma Co., Ltd., Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Okahashi
authors.affiliation: Preclinical Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kunimatsu
authors.affiliation: Preclinical Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Yabuki
mesh_terms: D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000633:toxicity*; D002478:Cells, Cultured; D005260:Female; D006728:Hormones / Q000096:biosynthesis*; D020128:Inhibitory Concentration 50; D008297:Male; D008782:Methylurea Compounds / Q000008:administration & dosage / Q000633:toxicity*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013256:Steroids / Q000096:biosynthesis*; D013844:Thiazoles / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D018927:Anti-Asthmatic Agents; D006728:Hormones; D008782:Methylurea Compounds; C000588743:N-(2-(2-((3-fluorophenyl)imino)-4-(4-morpholin-4-ylphenyl)-1,3-thiazol-3(2H)-yl)ethyl)-N'-methylurea; D013256:Steroids; D013844:Thiazoles
keywords: Endocrine organ; Endocrine toxicity; Inhibition; Rat; SMP-028; Steroidogenesis