Pharmacological overview of galactogogues

Abstract

Galactogogues are substances used to induce, maintain, and increase milk production, both in human clinical conditions (like noninfectious agalactias and hypogalactias) and in massification of production in the animal dairy industry. This paper aims to report the state of the art on the possible mechanisms of action, effectiveness, and side effects of galactogogues, including potential uses in veterinary and human medicine. The knowledge gaps in veterinary clinical practice use of galactogogues, especially in the standardization of the lactogenic dose in some pure drugs and herbal preparations, are reviewed.

Figure 1

Synthetics galactogogue drugs structure.

Figure 2

Proposed mechanism of action of dopamine 2 antagonists. In the pituitary gland, antagonists bind to the receptor (D2R) dopamine 2 and induce PRL gene expression, blood level of PRL increases, milk protein synthesis rate increases, and mammary epithelial cells (MEC) proliferation is stimulated.

Figure 3

Proposed mechanism of action of oxytocin (OT). This hormone induces contraction of the myoepithelial cells (green arrow), via a G protein receptor. OT also induces exocytosis of milk in MEC (blue arrow) by intracellular Ca²⁺ increased pathways. Myoepithelial cells contraction and MEC exocytosis induce milk ejection; the continued milk ejection results in a decrease of a protein milk synthesis reversible blocker: feedback inhibitor of lactation (FIL), and this milk and FIL removal of mammary gland will promote then the milk synthesis.

Figure 4

Proposed mechanism of action of recombinant bovine somatotropin (rBST). This hormone has direct effects on basal metabolic rate and breast parenchyma; the effects on the MEC (blue arrow) are mediated by rBST/ST-R complex, which stimulates JAK2/STAT5 pathway and by IGF-1R/IGF-1 which promotes and upregulates IRS/PI3K/(AKT/PKB)/mTOR and Ras/Raf/(MAPK/ERK) pathways. This will induce cell proliferation and survival and increase milk protein synthesis in MEC.

Figure 5

Proposed mechanism of action of thyrotropin releasing hormone (TRH). The TRH molecule binds to its receptor in lactotrophic cells of the pituitary gland and stimulates Ca²⁺/CaM release, which induces the PRL gene expression. Furthermore, the increase in intracellular CA²⁺/CaM stimulates the release of PRL stored in vesicles. This will increase PRL blood levels and promotes more milk synthesis.

Figure 6

Phytoestrogenic molecules present in some botanical galactogogues.

Figure 7

Proposed galactogogue mechanism of action of phytoestrogen molecules in anterior pituitary and mammary gland. The E2-like action may induce PRL expression in anterior pituitary lactotrophic cells and milk production in MEC by indeterminate pathways (?). In lactotrophic cells, upregulation of PRL gene expression and secretion occurs directly by E2R and indirectly by mE2R inducing D2R inhibition. In MEC, PRL-R and EGF-R expressions are induced and milk synthesis, cell proliferation, and survival gene expression are suggested.