Meyer M J, Capuco A V, Boisclair Y R, Van Amburgh M E
Department of Animal Science, Cornell University, Ithaca, New York 14850, USA.
J Endocrinol. 2006 Sep;190(3):819-27. doi: 10.1677/joe.1.06883.
Ovaries are absolutely required for development of the mammary parenchyma (PAR) in cattle, reflecting estrogen-dependent epithelial cell proliferation. However, the estrogen receptor (ER) that mediates the mammary estrogen effects, ERalpha, is absent in proliferating epithelial cells. In the mouse, this discrepancy is explained in part by the ability of the mammary fat pad (MFP) to synthesize epithelial cell mitogens such as IGF-I in response to estrogen. Consistent with a similar role for the bovine MFP, 30% of its fibroblasts and adipocytes were immunoreactive for ERalpha in prepubertal dairy heifers. To assess estrogen-dependent gene expression in the MFP, 16 prepubertal dairy heifers were randomly assigned to a 2x2 factorial. The first factor was ovarian status, with heifers undergoing bilateral ovariectomy or left intact at 4.6 months of age. The second factor was applied 30 days after surgery and consisted of injection of estrogen or excipient. After 3 days of injection, heifers were administered an intrajugular bolus of bromodeoxyuridine (BrdU) and slaughtered 2 h later. The estrogen injection, but not ovarian status, caused significant increases in the fraction of epithelial cells labeled with BrdU and produced tissue-specific effects on gene expression. In the PAR, estrogen injection increased IGF-I gene expression by twofold despite reductions of 50% or more in ERalpha mRNA abundance and the fraction of epithelial cells immunoreactive for ERalpha. The estrogen-dependent increase in IGF-I mRNA was greater in the MFP, presumably because estrogen failed to downregulate ERalpha expression in this mammary compartment. Finally, estrogen-responsiveness of the MFP appears unique among the bovine fat depots as estrogen injection did not induce IGF-I expression in its s.c. counterpart. Our data demonstrate that the bovine MFP is highly responsive to exogenous estrogen, consistent with a role for this tissue compartment in communicating its effects on epithelial cell proliferation.
卵巢是牛乳腺实质（PAR）发育绝对必需的，这反映了雌激素依赖性上皮细胞增殖。然而，介导乳腺雌激素作用的雌激素受体（ER）α在增殖的上皮细胞中并不存在。在小鼠中，这种差异部分是由于乳腺脂肪垫（MFP）能够响应雌激素合成上皮细胞有丝分裂原，如胰岛素样生长因子-I（IGF-I）。与牛MFP的类似作用一致，在青春期前的奶牛小母牛中，其30%的成纤维细胞和脂肪细胞对ERα呈免疫反应性。为了评估MFP中雌激素依赖性基因表达，将16头青春期前的奶牛小母牛随机分配到一个2×2析因设计中。第一个因素是卵巢状态，小母牛在4.6月龄时接受双侧卵巢切除术或保持完整。第二个因素在手术后30天应用，包括注射雌激素或赋形剂。注射3天后，给小母牛颈内注射一次溴脱氧尿苷（BrdU），并在2小时后屠宰。雌激素注射而非卵巢状态导致用BrdU标记的上皮细胞比例显著增加，并对基因表达产生组织特异性影响。在PAR中，尽管ERα mRNA丰度和对ERα呈免疫反应性的上皮细胞比例降低了50%或更多，但雌激素注射仍使IGF-I基因表达增加了两倍。雌激素依赖性的IGF-I mRNA增加在MFP中更大，可能是因为雌激素未能下调该乳腺区域中ERα的表达。最后，MFP的雌激素反应性在牛脂肪库中似乎是独特的，因为雌激素注射在其皮下对应物中并未诱导IGF-I表达。我们的数据表明，牛MFP对外源雌激素高度敏感，这与该组织区域在传递其对上皮细胞增殖的影响方面的作用一致。
