In this week’s post, we will highlight proteins specifically expressed in a tissue with extensive plasticity - the female mammary glands. The evolutionary origin of mammary and milk gland-like structures is believed to date all the way back to 300 million years ago, and glandular secretory apocrine-like units in the skin of synapsids, an ancestor to mammals.

The mammary gland develops from the epidermis and is mainly composed of branched columnar and cuboidal epithelial cells that form distinct lobes. Each female breast consists of 15-20 lobes, separated by dense connective tissue, that leads to terminal, smaller mammary lobules where milk is produced through apocrine secretion during the active stage of lactation. The lobes and lobules are connected to a duct system, the lactiferous duct, which accumulates through lactiferous sinuses and finally reaches the nipple.

The postnatal developmental phases of the mammary gland in females can be separated in four distinct stages; puberty, pregnancy, lactation and involution. In the stage of female puberty and menstrual cycles, the glands are stimulated to proliferate and form branches due to increasing concentration of progesterone and estrogen from the ovary. Mammary glands in males also develop during puberty, however the growth is very limited and the glands remain undifferentiated.

Myoepithelial cells are found in a discontinuous layer between the lobular epithelial cells and the basal lamina. They respond to oxytocin by contracting and stimulating secretion. During pregnancy, the mammary epithelial cells proliferate intensely due to the action of an array of several hormones. The number of mammary epithelial cells increase exponentially. This imposes the glands to undergo a drastic and remarkable morphological transformation in preparation for lactation. For this to happen, the key players; estrogen, progesterone, prolactin and placental lactogen carry out their specific function at distinct time-points in a beautifully orchestrated interplay. Progesterone and estrogen stimulate the proliferation of the mammary gland, but inhibit lactation before birth. Prolactin and human placental lactogen stimulate the terminal lobules to alveolar differentiation in late pregnancy. The alveolar cells produce a highly nutritious white fluid, rich in carbohydrates, proteins and lipids, we all know as milk.

After giving birth, the progesterone and estrogen levels drop which results in copious production of milk. Also, the plasma cell population increase significantly in the surrounding connective tissue during the later stages of pregnancy. Plasma cells produce secretory immunoglobulins (IgA), which is transferred through the milk to provide some degree of passive immunity to the infant. At the end of breastfeeding, most alveoli and ducts that develop during pregnancy undergo degeneration in a process called involution. In the pictures above, two proteins expressed in the active stage of lactation in the mammary gland can be visualized. Alpha lactalbumin (LALBA) is a principal protein of milk required for the proper function of the enzyme Lactose synthase in the mammary gland. Lactose synthase produce lactose; the major carbohydrate in milk. The Kappa casein, encoded by the CSN3 gene, is an important protein for the structure and stability of the micelle, a component in milk that makes it possible to deliver high amounts of protein and insoluble molecules to the infant. Besides these two proteins, another eight proteins expressed in the lactating mammary gland have been analyzed. To learn more about proteins important for other female organs pay a visit to the endometrial, ovarian and placental-specific proteome landing pages.

References

Junqueira LC, Carneiro J. (2005) Basic Histology: Text and Atlas, 11th edition.

McGraw-Hill Professional. Oftedal OT. The evolution of milk secretion and its ancient origins. Animal. 2012 Mar;6(3):355-68

Henninghausen L, Robinson GW. Information networks in the mammary gland. Nat Rev Mol Cell Biol. 2005 Sep;6(9):715-25

Feria Hikmet Noraddin