Prolactin is a hormone primarily produced by the pituitary gland, an endocrine gland at the base of the brain. It plays a role in various biological processes. While recognized for milk production after childbirth, its influence extends to other systems. Present in both males and females, it contributes to overall physiological regulation.
The Basic Building Blocks
Prolactin is a protein constructed from amino acids, which link in a specific linear order to form a polypeptide chain, its unique primary structure. Human prolactin, for example, consists of 199 amino acid residues. Its precise arrangement, determined by genetic information, serves as the hormone’s blueprint. Without this sequence, a functional molecule cannot form correctly.
Folding into a Three-Dimensional Molecule
Once formed, the linear amino acid chain folds into a specific three-dimensional shape, a process involving secondary structures like alpha-helices and beta-sheets. Alpha-helices are spiral-like, while beta-sheets are flatter, pleated arrangements. Prolactin’s structure is predominantly helical, with several alpha-helical regions.
These secondary structures pack to create the tertiary structure, the protein’s complete three-dimensional conformation. The stability of this unique shape is reinforced by three disulfide bonds. These are strong chemical links between sulfur atoms of cysteine residues within the polypeptide chain. This precise and stable folding is necessary for prolactin to function.
How Structure Enables Function
Prolactin’s three-dimensional shape enables it to bind to its target, the prolactin receptor (PRLR), on cell surfaces. This interaction is often described as a “lock-and-key” mechanism, where prolactin acts as the “key” fitting the “lock” of its receptor. The human prolactin molecule has specific binding sites interacting with the receptor’s extracellular domain.
One region on prolactin (site 1) binds to one receptor molecule, and a second site (site 2) binds to another, leading to receptor dimerization. This dimerization, or pairing, of two receptor molecules initiates intracellular signaling pathways for prolactin’s effects. Even slight alterations in prolactin’s three-dimensional structure, such as changes in its amino acid sequence or incorrect folding, disrupt these binding interactions. This structural compromise can impair receptor activation, reducing or eliminating its function.
Variations in Prolactin Structure
Prolactin exists in several forms (isoforms), varying primarily in size and modifications. The most common form, monomeric prolactin, is the standard 23 kDa (kilodalton) single polypeptide chain. Larger forms like “big” prolactin (approximately 50-60 kDa) and “big-big” prolactin (over 100 kDa) also exist.
“Big” prolactin often represents dimeric forms or prolactin bound to other proteins. “Big-big” prolactin is a macroprolactin complex, typically formed when prolactin binds to immunoglobulin G (IgG) antibodies. These larger forms may have reduced biological activity compared to the monomeric form, as their size hinders effective receptor binding or passage through capillary walls. Post-translational modifications, such as glycosylation (adding sugar groups) and phosphorylation (adding phosphate groups), alter prolactin’s structure and activity. Glycosylation, for instance, affects the hormone’s stability and clearance rate from the bloodstream.
What Happens When Prolactin Structure is Abnormal
When prolactin’s structure is incorrectly formed by misfolding or genetic mutations, its biological activity is compromised. An incorrectly folded prolactin molecule may not bind effectively to its receptor, preventing signaling. This can lead to prolactin resistance, where despite normal or elevated circulating prolactin, cells do not respond appropriately.
Conversely, some structural abnormalities might lead to a prolactin molecule that is more stable in the bloodstream but less active at the receptor, contributing to hyperprolactinemia. This refers to an excess of prolactin in the blood, arising from various causes, including less active but persistent forms. Such structural issues disrupt physiological processes dependent on proper prolactin signaling.
References
Prolactin: structure, function, and regulation. Physiological Reviews, 80(3), 1145-1200.
The prolactin receptor: signaling mechanisms and activation of transcription factors. Journal of Biological Chemistry, 277(14), 12227-12236.
Macroprolactinemia: clinical significance and analytical aspects. Clinical Chemistry, 54(1), 67-78.