Growth hormone treatment induces mammary gland hyperplasia in aging primates.
The decline of growth hormone (GH) and insulin-like growth factor I (IGF-I) production during aging has been likened to the decrease in gonadal steroids in menopause. The repletion of GH/IGF-I levels in aging individuals is suggested to restore the lean tissue anabolism characteristic of youth. In addition to anabolic effects on musculo-skeletal tissues, GH also stimulates mammary glandular growth in some species, although its effects on primate mammary growth remain unclear. Some clinical observations implicate GH in human mammary growth, for example, gynecomastia occurs in some children treated with GH (ref. 6), and tall stature and acromegaly are associated with an increased incidence of breast cancer. To investigate the effects of GH/IGF-I augmentation on mammary tissue in a model relevant to aging humans, we treated aged female rhesus monkeys with GH, IGF-I, GH + IGF-I or saline diluent for 7 weeks. IGF-I treatment was associated with a twofold increase, GH with a three- to fourfold increase, and GH + IGF-I with a four'-to fivefold increase in mammary glandular size and epithelial proliferation index. These mitogenic effects were directly correlated with circulating GH and IGF-I levels, suggesting that either GH or its downstream effector IGF-I stimulates primate mammary epithelial proliferation.
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Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892-1770, USA.
Zhou
J
J
Adesanya
O O
OO
Wang
J
J
LeRoith
D
D
Bondy
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CA
D000375:Aging / Q000502:physiology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D006965:Hyperplasia; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D019394:Ki-67 Antigen / Q000032:analysis; D008253:Macaca mulatta; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D008940:Mitotic Index / Q000187:drug effects; D011981:Receptors, Prolactin / Q000096:biosynthesis; D011986:Receptors, Somatotropin / Q000096:biosynthesis; D012044:Regression Analysis
D019394:Ki-67 Antigen; D011981:Receptors, Prolactin; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone