General Structure and Duct System
Anatomically, the gland consists of 15–20 lobes. Their hemispherical shape and volume are supported by an abundant layer of adipose tissue. The morphological hierarchy is organized as follows: lobe $\rightarrow$ lobule $\rightarrow$ terminal secretory unit.
The milk outflow system forms a complex network of branching tubes. Intralobular ducts merge to form interlobular ducts, which subsequently unite into a single lactiferous duct for each lobe. All lobular ducts converge toward the nipple. Before entering the nipple, they dilate to form lactiferous sinuses, which serve as temporary reservoirs for milk accumulation before nursing. At the tip of the nipple, the ducts narrow and open externally via lactiferous orifices. Notably, there are 15–20 ducts but only 8–15 orifices because several pathways fuse distally to the sinuses.
As the ducts increase in size, the lining epithelium changes: from simple cuboidal in smaller branches, through stratified columnar and stratified cuboidal, to stratified squamous keratinized epithelium near the nipple.
Histophysiology in Resting and Lactating States
In the non-lactating mammary gland, secretory terminal units are poorly developed and appear as blind-ended tubules, termed lactiferous alveolar ducts. Due to the extensive branching of the duct system, the gland is classified as a compound gland.
Toward the end of pregnancy, under the influence of high concentrations of progesterone, the gland undergoes structural transformation. The lactiferous ducts proliferate, forming new fully developed terminal structures known as alveoli (acini). These are hollow sacs whose walls consist of two primary cell types:
- Lactocytes (secretory cells): Arranged in a single layer on the basement membrane, they are cuboidal in shape with rounded nuclei and microvilli, and contain intracellular canaliculi for protein transport.
- Myoepithelial cells: Basket-like cells that surround the alveolus externally and feature characteristic rod-shaped nuclei. Their primary function is contraction to expel milk into the ducts.
Nipple and Areola Histology
Histologically, the nipple is a skin thickening penetrated by the lactiferous duct system. The epidermis and dermis in this region contain numerous melanocytes, accounting for its distinct pigmentation.
The papillary dermis contains a high density of sensory nerve endings. Their stimulation during suckling provides the afferent limb of the neuroendocrine milk ejection reflex. The reticular dermis contains bundles of smooth muscle cells (myocytes) that circumferentially encircle the excretory ducts to aid in their evacuation.
While hair follicles are absent on the nipple, sebaceous glands are present, and their ducts may open directly into the lactiferous pathways. Sweat glands are also found within the areola.
Mechanisms of Cellular Milk Secretion
Lactocytes utilize different secretory strategies for releasing milk components, which are clearly visible on histological preparations:
- Merocrine Mechanism (for proteins, lactose, and salts).
The synthesis of casein (the primary milk protein) occurs in the abundant rough endoplasmic reticulum. The Golgi apparatus packages these proteins into secretory granules. The granules migrate to the apical pole of the lactocyte, their membranes fuse with the plasmalemma, and the contents are released via exocytosis without damaging the cell itself.
- Apocrine Mechanism (for lipids).
Large triglyceride droplets accumulate at the apical pole of the cell. The lipid droplet bulges against the plasma membrane, which wraps around it before the droplet pinches off along with a small rim of cytoplasm and plasma membrane. Consequently, the apical portion of the lactocyte undergoes temporary structural loss.
Hierarchy of Hormonal Regulation
Mammary gland function is regulated by a classical hypothalamic-pituitary-target organ axis:
- Central Control: The hypothalamus releases thyrotropin-releasing hormone (TRH), which stimulates the anterior pituitary, and dopamine, which inhibits it.
- Prolactin: Produced by the anterior pituitary gland, it exerts a direct effect on lactocytes, triggering intensive synthesis of milk components. It also indirectly maintains the corpus luteum, which secretes progesterone.
- Oxytocin: Synthesized in the hypothalamus and released from the posterior pituitary gland. It drives milk ejection by binding to receptors on myoepithelial cells, inducing their contraction.
- Sex Steroids: Estrogens stimulate the proliferation and branching of the ducts, whereas progesterone is essential for the growth and development of the secretory alveoli.