Submitted to: Journal of Dairy Science
Publication Type: Peer reviewed journal
Publication Acceptance Date: 1/8/2003
Publication Date: 1/8/2003
Citation: BERRY, S.D., JOBST, P.M., ELLIS, S.E., HOWARD, R.D., CAPUCO, A.V., AKERS, R.M. MAMMARY EPITHELIAL PROLIFERATION AND ESTROGEN RECEPTOR-ALPHA EXPRESSION IN PREPUBERTAL HEIFERS: EFFECTS OF OVARIECTOMY AND AND GROWTH HORMONE. JOURNAL OF DAIRY SCIENCE. vol. 86, pp. 2098-2105, 2003. Interpretive Summary: Although most mammary growth occurs during pregnancy, the extent of mammary growth and development that occurs prepubertally can influence lifetime milk production. It is during the prepubertal period that the cellular framework for future mammary growth and milk secretion is established. Factors that impede or enhance prepubertal mammary development can impact the lifetime milk production of a dairy cow. Ovarian steroids, particularly estrogens, are known to simulate prepubertal mammary growth. Additionally, administration of growth hormone can enhance mammary growth prepubertally. We have evaluated the relationship between the cellular sensing mechanism for responding to estrogens (estrogen receptor) and cell growth in the mammary gland. The hypothesis tested was that growth hormone increased sensitivity of the mammary gland to estrogens (by increasing expression of estrogen receptor) and thus increased mammary growth. Data did not support this hypothesis, suggesting that growth hormone stimulates mammary growth via an estrogen-independent mechanism. After removal of the ovaries (estrogen source), prepubertal mammary growth was markedly reduced, but the percentage of mammary cells expressing estrogen receptor was increased. The latter observation may have been due to the negative impact of estrogen removal on mammary development with the accompanying production of cells without estrogen receptor. Further study is necessary to elucidate the relationship between sensitivity of mammary cells to estrogens and mammary development.
Technical Abstract: The objectives were to determine the effects of ovariectomy and growth hormone on mammary epithelial cell proliferation and estrogen receptor-alpha (ERa) expression within the bovine mammary gland. Two experiments were performed. In the first experiment, eight Holstein heifer calves aged between one and three months were ovariectomized, while six calves served as controls. At six months of age, calves were treated with bromodeoxyuridine (BrdU) to label proliferating cells and sacrificed two hours later. Coinciding with reduced mammary mass (304 ± 25g vs. 130 ± 21g), proliferation of mammary epithelial cells was significantly lower in ovariectomized heifers compared to control heifers (2.24% vs. 0.25%). ERa expression was restricted to mammary epithelial cells, and was not observed within intra-lobular stroma of parenchymal tissue. The proportion of ERa positive cells was significantly higher in ovariectomized heifers than controls (36.1% ± 2.2 vs. 46.7% ± 2.4). In the second experiment, mammary biopsies were taken from five six-month-old heifers, immediately proceeding and seven days following a single injection of bovine growth hormone. Mammary epithelial cell proliferation (assessed by incorporation of 3H-thymidine) was increased by growth hormone. Conversely, the proportion of ERa positive mammary epithelial cells was not influenced by growth hormone. In conclusion, reduced mammary epithelial cell proliferation following ovariectomy was associated with an increase in ERa labeling, whereas increased proliferation caused by bovine growth hormone was not associated with changes in ERa labeling.