title: Inhibition of peripubertal sheep mammary gland development by cysteamine through reducing progesterone and growth factor production.
abstract: Cysteamine has been used for treating cystinosis for many years, and furthermore it has also been used as a therapeutic agent for different diseases including Huntington's disease, Parkinson's disease (PD), nonalcoholic fatty liver disease, malaria, cancer, and others. Although cysteamine has many potential applications, its use may also be problematic. The effects of low doses of cysteamine on the reproductive system, especially the mammary glands are currently unknown. In the current investigation, low dose (10 mg/kg BW/day) of cysteamine did not affect sheep body weight gain or organ index of the liver, spleen, or heart; it did, however, increase the levels of blood lymphocytes, monocytes, and platelets. Most interestingly, it inhibited mammary gland development after 2 or 5 months of treatment by reducing the organ index and the number of mammary gland ducts. Plasma growth hormone and estradiol remained unchanged; however, plasma progesterone levels and the protein level of HSD3β1 in sheep ovaries were decreased by cysteamine. In addition to steroid hormones, growth factors produced in the mammary glands also play crucial roles in mammary gland development. Results showed that protein levels of HGF, GHR, and IGF1R were decreased after 5 months of cysteamine treatment. These findings together suggest that progesterone and local growth factors in mammary glands might be involved in cysteamine initiated inhibition of pubertal ovine mammary gland development. Furthermore, it may lead to a reduction in fertility. Therefore, cysteamine should be used with great caution until its actions have been further investigated and its limitations overcome.
authors.affiliation: College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao 266109, PR China; Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao 266109, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao 266109, PR China; College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, PR China.
authors.forename: Yanni
authors.initials: Y
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, PR China.
authors.forename: Hongfu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Shouguang Hongde Farmer Co., Weifang 262700, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Kou
authors.affiliation: Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao 266109, PR China; College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, PR China.
authors.forename: Lan
authors.initials: L
authors.lastname: Li
authors.affiliation: College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao 266109, PR China.
authors.forename: Xinqi
authors.initials: X
authors.lastname: Liu
authors.affiliation: College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao 266109, PR China; Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao 266109, PR China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao 266109, PR China; College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, PR China.
authors.forename: Liantao
authors.initials: L
authors.lastname: Cui
authors.affiliation: Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao 266109, PR China; College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, PR China.
authors.forename: Meiqiang
authors.initials: M
authors.lastname: Chu
authors.affiliation: Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao 266109, PR China; College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.affiliation: College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, PR China. Electronic address: mlj020963@hotmail.com.
authors.forename: Lingjiang
authors.initials: L
authors.lastname: Min
mesh_terms: D000818:Animals; D001835:Body Weight; D003543:Cysteamine / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000097:blood; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000254:growth & development; D011374:Progesterone / Q000097:blood*; D012741:Sexual Maturation; D012756:Sheep / Q000254:growth & development / Q000502:physiology*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D011374:Progesterone; D004958:Estradiol; D003543:Cysteamine
keywords: Cysteamine; Development; Growth factors; Inhibition; Mammary gland; Progesterone