- In physiological hyperprolactinemia as in lactation, the endochondral bone growth is markedly enhanced, leading to elongation of long bone. This lactation-induced bone elongation could be abolished by inhibitor of prolactin—bromocriptine. However, how bromocriptine altered the expression of chondroregulatory proteins in the growth plate cartilage was not known. In the current study, we used a quantitative immunohistochemical analysis to determine the expression of secretory proteins and transcription factors known to control the growth plate chondrocyte proliferation and differentiation [i.e., parathyroid hormone-related protein (PTHrP), PTHrP receptor, Indian hedgehog (Ihh), runt-related transcription factor 2 (Runx2) and SRY-box containing gene 9 (Sox-9)], in bromocriptine-treated lactating rats. The results showed that bromocriptine markedly increased Ihh expression in hypertrophic chondrocytes during early and mid-lactation, while the expression of PTHrP receptor, but not its ligand PTHrP, was upregulated in the proliferative and hypertrophic zones during mid- and late lactation. In contrast, the expression of Runx2, an important transcription factor for chondrocyte differentiation, was suppressed in the hypertrophic chondrocytes of bromocriptine-treated rats. In conclusion, bromocriptine increased Ihh and PTHrP receptor expressions and decreased Runx2 expression, which might, in turn, enhance chondrocyte proliferation and delay chondrocyte hypertrophy, thereby slowing down endochondral bone growth. This finding could explain how bromocriptine compromised the lactation-induced bone elongation.