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Title: QUANTITATIVE ANALYSIS OF ESTROGEN-RELATED RECEPTOR ALPHA-1 (ERRA), ESTROGEN RECEPTORS ALPHA (ERA), AND BETA (ERB) AND PROGESTERONE (PR) DURING BOVINE MAMMARY GLAND DEVELOPMENT, & MAPPING OF THE RECEPTORS TO THE BOVINE GENOME.

Author
item Connor, Erin
item Wood, David
item Sonstegard, Tad
item MOTA, A - EMBRAPA
item Bennett, Gary
item WILLIAMS, J - ROSLIN INSTITUTE
item Capuco, Anthony

Submitted to: Journal of Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/31/2005
Publication Date: 3/24/2005
Citation: Connor, E.E., Sonstegard, T.S., Mota, A.F., Wood, D.L., Bennett, G.L., Williams, J.L., Capuco, A.V. 2005. Chromosomal mapping and quantitative analysis of estrogen-related receptor alpha-1 (ERRa), estrogen receptors alpha (ERa), and beta (ERb) and progesterone (PR) in the bovine mammary gland. Journal of Endocrinology. 185:593-609.

Interpretive Summary: Ovarian hormones are important regulators of mammary gland function. The molecules (receptors) within mammary cells that sense and mediate the response to ovarian steroids have been identified. These include estrogen receptors alpha and beta and progesterone receptors. Additionally, a receptor that bears marked similarity to estrogen receptors, but does not bind estrogen, has been identified and is known as the estrogen-related receptor. This later receptor has been implicated as a regulator of estrogen responsive genes even in the absence of estrogen. It also appear to promote mitochondria formation to meet energy demands. We evaluated the expression of these molecules during mammary gland development and function. Estrogen receptor-alpha and progesterone receptor were expressed during all physiological stages and were correlated in their level of expression. Estrogen receptor-beta was found in very low concentration in mammary tissues, suggesting that it is not a major regulator in bovine mammary gland. In contrast, the estrogen-related receptor was found at moderate concentrations during all physiological stages, supporting a role for the receptor in bovine mammary gland biology.

Technical Abstract: Steroid receptors are key transcriptional regulators of mammary growth, development and lactation. Expression of estrogen receptors alpha (ERá) and beta (ERâ), progesterone receptor (PR), and estrogen-related receptor alpha-1 (ERRá) have been evaluated in bovine mammary gland. The ERRá is an orphan receptor that, in other species and tissues, appears to function in regulation of estrogen-response genes including lactoferrin and medium chain acyl CoA dehydrogenase and in mitochondrial biogenesis. Expression of ERá, ERâ, PR, and ERRá was characterized in mammary parenchyma obtained from multiple stages of bovine mammary gland development using quantitative real-time RT-PCR. Expression was evaluated in prepubertal heifers, primigravid cows, lactating non-pregnant cows, lactating pregnant cows and non-lactating pregnant cows (n = 4 to 9 animals/stage). In addition, ERá, ERâ, PR, and ERRá were mapped to chromosomes 9, 10, 15 and 29, respectively, by linkage and radiation hybrid mapping. Results indicated that expression of ERá, PR, and ERRá were largely coordinately regulated and present in significant quantity during all physiological stages evaluated. In contrast, ERâ transcripts were present at very low concentration during all stages. Furthermore, no ERâ protein could be detected in bovine mammary tissue by IHC. The ERá and PR proteins were detected during all physiological states, including lactation. Our results demonstrate the presence of ERá, PR, and ERRá during all physiological stages and suggest a functional role for ERRá and a relative lack of function for ERâ in bovine mammary gland development and lactation.