Ontogenic and nutritional regulation of steroid receptor and IGF-I transcript abundance in the prepubertal heifer mammary gland

Abstract

In prepubertal cattle, mammary development is characterized by the growth of an epithelial-rich parenchyma (PAR) into the mammary fat pad (MFP). This proliferation and accumulation of mammary epithelial cells require estrogen. Paradoxically, both epithelial cell proliferation and PAR accumulation rate decline with rising plasma estrogen as puberty approaches. The possibility that variation in abundance of estrogen receptors (ERs) in PAR or MFP accounts for a portion of these effects has not been examined in cattle. Additionally, we recently demonstrated that MFP is highly responsive to exogenous estrogen, suggesting that this tissue may play a role in coordinating estrogen's effects on PAR; however, the developing bovine MFP has yet to be studied in detail. To address these hypotheses, Holstein heifers were assigned to planes of nutrition supporting body growth rates of 950 (E) or 650 (R) g/day and harvested every 50 kg from 100 to 350 kg body weight (BW). Post-harvest, their mammary glands were dissected into PAR and MFP compartments. Transcript abundance of genes encoding members of the ER family (ERa, ERb, and estrogen-related receptor a-1 (ERRa)) and estrogen-responsive genes (IGF-I and progesterone receptor (PR)) were measured in both mammary compartments by quantitative real-time RT-PCR. Significant expression was detected for all genes in both compartments, with the exception of the ERb gene. Transcript abundance of both ERa and IGF-I decreased linearly with increasing BW within both compartments. ERRa and PR expressions decreased with increasing BW in PAR but not in MFP. Nutrition stimulated ERa and ERRa expression in the PAR but had no effect on IGF-I or PR in either PAR or MFP. Overall, ERa and IGF-I transcript abundance are consistent with the drop in mammary epithelial cell proliferation and PAR accretion observed over development, but do not support a negative effect of nutrition on PAR growth.

Diverse and Active Roles for Adipocytes During Mammary Gland Growth and Function

“…Furthermore, Richert and Wood localized IGF-I mRNA expression within stromal tissue of the mammary fat pad, which clearly included adipocytes [76], consistent with the expression of IGF-I by subscapular adipose tissue in rats [77]. Along these lines, we established that IGF-I mRNA expression was increased in the proximity of the parenchymal tissue within the mammary glands of ewe lambs [78], whereas this was not the case in heifers [73]. This difference may reflect differences in the age or parenchymal composition of these species.…”

“…Further confusion regarding this matter arises when discussing the ER–α and ER–β isoforms given that the predominant stromal isoform in mice appears to be ER-β [71] whereas both isoforms have been localized to the stroma of the normal human breast [72]. Meanwhile, ER-β was undetectable in the mammary gland stroma from heifers [73]. …”

“…One potentially-important finding regarding local IGF-I expression concerns its expression in the mammary fat pad compared to other adipose depots. Interestingly, in both rats [77] and heifers [73] there was the general finding that the inductive effects of estrogen on IGF-I expression occurred moreso in the mammary fat pad than in other adipose depots. These data further support the idea that adipocytes within the mammary glands may have unique properties compared to those at other sites.…”

The effect of calf nutrition on the performance of dairy herd replacements

“…However, Meyer et al (2006a) having examined heifers at up to 350 kg found no effect of increased nutrient intake on mammary parenchyma DNA content concluding that age at which mammary samples are taken, and not level of nutrient intake, was the main determinant of pre-pubertal mammary development. Subsequent follow-up studies found minimal effects of elevated levels of nutrition on the expression of a number of genes (Meyer et al, 2007), mammary epithelial cell proliferation or the rate of parenchyma DNA accretion (Meyer et al (2006b). Shamay et al (2005), Bar-Peled et al (1997) and Drackley et al (2007) are the only studies to find a significant positive relationship between level of pre-weaning nutrition and subsequent milk production.…”

Alternativas en el manejo de la mastitis en novillas

“…Al inicio de la pubertad se inician los ciclos estrales de 21 días, que afectan marcadamente el desarrollo de la glándula mamaria. Se empiezan a expresar los receptores para progesterona (PR) y estrógenos (ER , ERß, ERRs) en la glándula que modulan la influencia de las hormonas esteriodales en la proliferación del epitelio mamario (15)(16)(17). En los experimentos clásicos de Sinha y Tucker (18) se demostró que durante el estro, la síntesis de DNA se incrementa en 115% y que luego esta se disminuye lentamente en el metaestro y el diestro hasta que alcanza su punto más bajo antes del estro.…”