Breast development, also known as mammogenesis, is a complex biological process in primates that takes place throughout a females life. It occurs across several phases, including prenatal development, puberty, and pregnancy. At menopause, breast development ceases and the breasts atrophy. Breast development results in prominent and developed structures on the chest known as breasts in primates, which serve primarily as mammary glands. The process is mediated by an assortment of hormones (and growth factors), the most important of which include estrogen, progesterone, prolactin, and growth hormone. Biochemistry
Hormones
The master regulators of breast development are the steroid hormones, estrogen and progesterone, growth hormone (GH), mostly via its secretory product, insulin-like growth factor 1 (IGF-1), and prolactin. These regulators induce the expression of growth factors, such as amphiregulin, epidermal growth factor (EGF), IGF-1, and fibroblast growth factor (FGF), which in turn have specific roles in breast growth and maturation.At puberty, gonadotropin-releasing hormone (GnRH) is secreted in a pulsatile manner from the hypothalamus. GnRH induces the secretion of the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), from the pituitary gland. The secreted gonadotropins travel through the bloodstream to the ovaries and trigger the secretion of estrogen and progesterone in fluctuating amounts during each menstrual cycle. Growth hormone (GH), which is secreted from the pituitary gland, and insulin-like growth factor 1 (IGF-1), which is produced in the body in response to GH, are growth-mediating hormones.
As both the IGF-1R and the EGFR are independently essential for mammary gland development, and as combined application of IGF-1 and EGF, through their respective receptors, has been found to synergistically stimulate the growth of human breast epithelial cells, these growth factor systems appear to work together in mediating breast development.Elevated levels of HGF and, to a lesser extent, IGF-1 (by 5.4-fold and 1.8-fold, respectively), in breast stromal tissue, have been found in macromastia, a very rare condition of extremely and excessively large breast size. Exposure of macromastic breast stromal tissue to non-macromastic breast epithelial tissue was found to cause increased alveolar morphogenesis and epithelial proliferation in the latter. A neutralizing antibody for HGF, but not for IGF-1 or EGF, was found to attenuate the proliferation of breast epithelial tissue caused by exposure to macromastic breast stromal cells, potentially directly implicating HGF in the breast growth and enlargement seen in macromastia. Also, a genome-wide association study has highly implicated HGF and its receptor, c-Met, in breast cancer aggressiveness. Lactation
Upon parturition (childbirth), estrogen and progesterone rapidly drop to very low levels, with progesterone levels being undetectable. Conversely, prolactin levels remain elevated. As estrogen and progesterone block prolactin-induced lactogenesis by suppressing prolactin receptor (PRLR) expression in breast tissue, their sudden absence results in the commencement of milk production and lactation by prolactin. Expression of the PRLR in breast tissue may increase by as much as 20-fold when estrogen and progesterone levels drop upon childbirth.