Parity-induced decrease in systemic growth hormone alters mammary gland signaling: a potential role in pregnancy protection from breast cancer.
Early full-term pregnancy is an effective natural protection against breast cancer in both humans and experimental rodents. The protective effect of an early pregnancy is, in part, linked to changes in circulating hormones that are involved in both normal breast development and breast cancer. For example, a reduction in circulating growth hormone (GH) has been shown to protect rats from carcinogen-induced mammary tumors. We examined the ability of a full-term pregnancy to alter the endocrine GH/insulin-like growth factor-I (IGF-I) axis and how this change affected normal mammary gland function in two commonly used rat models (Sprague-Dawley and Wistar Furth). Circulating GH and IGF-I were measured in blood drawn every 30 minutes from parous and age-matched virgin female rats. Mean serum GH levels were significantly decreased (P < 0.01) in parous compared with age-matched virgin rats for both strains. Changes in GH levels were independent of estrous cycle, indicated by a significant (P < 0.05) reduction in circulating levels of GH during estrus and diestrus in both parous strains. Despite the decrease in circulating GH, pituitary GH mRNA levels were unaltered in parous rats. Circulating IGF-I and hepatic IGF-I mRNA were also unaltered by parity in either rat strain. Immunoblot analysis of mammary glands showed decreases in phosphorylation of signal transducer and activator of transcription 5A and Janus-activated kinase 2, suggesting reduced action of GH in the mammary gland. Therefore, although the parity reduction in circulating GH does not affect circulating IGF-I levels, it is possible that reduced GH acts directly at the mammary gland and may play a role in pregnancy protection from breast cancer.
Breast Center, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Robert K
RK
Dearth
David A
DA
Delgado
Jill K
JK
Hiney
Thushangi
T
Pathiraja
Steffi
S
Oesterreich
Dan
D
Medina
W Les
WL
Dees
Adrian V
AV
Lee
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D010298:Parity; D011247:Pregnancy; D011270:Pregnancy, Animal; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone