Regulation of Gene Expression in the Bovine Mammary Gland by Ovarian Steroids

Abstract

It is well established that estrogen is required for mammary epithelial cell proliferation and ductal development in the growing animal, and that lobuloalveolar development during gestation is dependent on progesterone. The effects of these steroid hormones on gene expression in the mammary gland are mediated primarily by their respective nuclear hormone receptors, which function as hormone-bound transcription factors. To gain insight into how estrogen and progesterone regulate mammary gland growth and function in cattle, we and others have characterized the expression patterns of their cognate nuclear hormone receptors in the bovine mammary gland throughout development, pregnancy, and lactation. This work has identified a lack of expression of estrogen receptor beta and a greater abundance of progesterone receptor during lactation in the bovine mammary gland, compared with the rodent gland. We speculate that interactions among the estrogen receptor isoforms that regulate progesterone receptor expression may contribute to these species differences. Further, demonstrated expression of substantial quantities of estrogen receptor within the prepubertal bovine mammary fat pad, along with coordinated insulin-like growth factor-I expression, suggests that this tissue may stimulate parenchymal growth via an estrogen-responsive paracrine mechanism. In addition, the recent availability of bovine genomic sequence information and microarray technologies has permitted the study of global gene expression in the mammary gland in response to the steroid environment. We have identified more than 100 estrogen-responsive genes, of which the majority are novel estrogen gene targets. Estrogen-induced changes in gene expression were consistent with increased mammary epithelial cell proliferation, increased extracellular matrix turnover in parenchyma, and increased extracellular matrix deposition in the fat pad. A comparison of estrogen-responsive genes in the mammary glands of humans, mice, and cattle suggests considerable variation among species, as well as potential differences in regulatory elements in common estrogen receptor gene targets. Continuing studies using advanced molecular techniques should assist in elucidating the complex regulation of mammary function at the transcript level.

Nitric oxide concentrations in mammary quarters during heifer mastitis

“…This result could be associated with two factors. It might be related to major development of the mammary gland during pregnancy, such that lobuloalveolar systems are formed and secretion starts by induction of elevated hormones such as estrogen and progesterone during pregnancy (Tucker, 1987;Connor et al, 2007). In addition, blood circulation in this stage normally increases and many nitrogenous substrates are carried to the mammary gland by red blood cells (Baumrucker, 1985).…”

Effect of pregnancy and feeding level on cell turnover and expression of related genes in the mammary tissue of lactating dairy cows

“…In fact, it has been well documented that oestrogen inhibits milk synthesis in lactating cows (Akers, 2002), so the increased ERa may be involved in mediating the negative effect of oestrogen on milk yield. This is supported by the observation that the mRNA abundance of IGF-I and IGFBP-5 was unaffected by pregnancy, since the IGF system is believed to be involved in mediating the effect of oestrogen on cell proliferation (Hanstein et al, 2004;Connor et al, 2007). Thus, in animals with concurrent pregnancy and lactation, the effects of oestrogen may be different from those in non-lactating animals with developing mammary glands such as prepubertal and pubertal animals.…”

Repression of Lim only protein 4-activated transcription inhibits proliferation and induces apoptosis of normal mammary epithelial cells and breast cancer cells

“…Taken together, our data indicate that LMO4 has similar cellular effects in normal mammary epithelial cells and breast cancer cells, and also provide direct evidence for the idea that normal development and carcinogenesis share conserved molecular mechanisms. including sex hormones, growth factors and cytokines, regulate these processes [2,[4][5][6]. Any perturbation in this complex regulatory system may lead to mammary neoplasia [1,5].…”