Endocrine hormones and local signals during the development of the mouse mammary gland

Abstract

Most of mammary gland development occurs postnatally under the control of female reproductive hormones, which in turn interact with other endocrine factors. While hormones impinge on many tissues and trigger very complex biological responses, tissue recombination experiments with hormone receptor-deficient mammary epithelia revealed eminent roles for estrogens, progesterone, and prolactin receptor (PrlR) signaling that are intrinsic to the mammary epithelium. A subset of the luminal mammary epithelial cells expresses the estrogen receptor α (ERα), the progesterone receptor (PR), and the PrlR and act as sensor cells. These cells convert the detected systemic signals into local signals that are developmental stage-dependent and may be direct, juxtacrine, or paracrine. This setup ensures that the original input is amplified and that the biological responses of multiple cell types can be coordinated. Some key mediators of hormone action have been identified such as Wnt, EGFR, IGFR, and RANK signaling. Multiple signaling pathways such as FGF, Hedgehog, and Notch signaling participate in driving different aspects of mammary gland development locally but how they link to the hormonal control remains to be elucidated. An increasing number of endocrine factors are appearing to have a role in mammary gland development, the adipose tissue is increasingly recognized to play a role in endocrine regulation, and a complex role of the immune system with multiple different cell types is being revealed. For further resources related to this article, please visit the WIREs website.

Progesterone and Overlooked Endocrine Pathways in Breast Cancer Pathogenesis

“…A number of other hormones impinge on the basic regulatory network controlled by the ovarian hormones (71). They may serve to fine-tune the system or have distinct functions.…”

Hormone-Sensing Mammary Epithelial Progenitors: Emerging Identity and Hormonal Regulation

“…It should also be noted that data derived from immortilised normal human breast cell lines, or primary organoid cultures must be assessed with caution, as even short-term culture of primary MECs has been shown to induce modifications in the expression of lineagespecific markers and stem/progenitor activity [6,54]. Nonetheless, the well-established dissociation of ERα and PGR action between pubertal mammary growth and TDLU/LA development during adulthood, respectively (reviewed in [55]), suggests a spatiotemporal regulation of ERα and PGR action that would logically make use of Boestrogen-dominant^and Bprogesterone-dominant^progenitors. A recent genome-wide investigation in breast cancer offers an attractive mechanistic basis to explain the independent actions of oestrogen and progesterone in normal mammary development, finding that PGR had the ability to re-program the ERα transcriptional landscape in human breast cancer [56].…”

“…Such plasticity suggests the existence of signalling networks that regulate the expansion and contraction of the HS-MEC population. Brisken, and Tanos et al thoroughly review the effects of oestrogen and progesterone on ductal outgrowth, and lobuloalveolar development at the cellular and molecular level [55,57,58]. Beyond these major hormonal players are additional endocrine and paracrine factors that powerfully regulate the HS-MEC population.…”

Expression of NGF, BDNF and their high-affinity receptors in ovine mammary glands during development and lactation

“…Intercellular signals of mammary microenvironment essential for normal development have been described, but they are not fully elucidated (McCave et al 2010;Brisken and Ataca 2015). Interactions between parenchyma and mammary fat pad are also demonstrated in prepubertal ewes (Hovey et al 1998), suggesting the presence of epithelial paracrine factors that would exert a positive feedback on the surrounding stroma.…”